Selected Infections of the GI Tract and Liver

By Rodrigo Burgos, Pharm.D., AAHIVP; and Mia Schmiedeskamp-Rahe, Pharm.D., Ph.D., BCPS

Reviewed by Kevin W. Garey, Pharm.D., M.S.; Ezra P. Mell, Pharm.D., M.S.E., BCPS; and Lisa Avery, Pharm.D., BCPS

LEARNING OBJECTIVES

1. Design a treatment plan for a patient with fungal or viral esophageal infection. 2. Construct an optimal treatment plan for managing Clostridium difficile–associated diarrhea, taking into account disease severity and recurrence. 3. Design a plan for treating proctocolitis or proctitis secondary to sexually transmitted organisms. 4. Recommend an empiric antibiotic regimen for the most common infections of the biliary system according to severity. 5. Select a strategy for preventing GI infections secondary to surgery or procedures. 6. Design and monitor pharmacologic therapy for treating various intestinal and liver parasites.

INTRODUCTION ABBREVIATIONS IN THIS CHAPTER AE Alveolar echinococcosis The digestive system or GI tract is a diverse set of organs including CDI Clostridium difficile infection the oropharynx, esophagus, stomach, small and large intestines, rec- CE Cystic echinococcosis tum, pancreas, and hepatobiliary system. These tissues are exposed CMV Cytomegalovirus to the environment, including microbes constituting the host micro- ERCP Endoscopic retrograde biome and pathogens. The microbiome and the immune system of cholangiopancreatography the GI tract protect against pathogenic organisms, but the GI tract FMT Fecal microbiota transplantation is nevertheless vulnerable to infection by viruses, bacteria, fungi, HSV Herpes simplex virus and parasites ranging from single-celled amoebas to multicellular IDSA Infectious Diseases Society of helminths. America This chapter focuses on selected infections of the GI tract and SSI Surgical site infection liver. A complete discussion of infections common in the develop- TACE Transarterial chemoembolization ing world is outside the scope of this chapter; however, some of these infections will be mentioned for the benefit of those practicing Table of other common abbreviations. abroad or among immigrant populations.

OROPHARYNGEAL AND ESOPHAGEAL INFECTIONS In the patient with immunocompromise, infectious esophagitis is most commonly associated with Candida spp., herpes simplex virus (HSV), and cytomegalovirus (CMV); it is less commonly associated with Cryptosporidium, Mycobacterium avium complex, histoplasmosis, leishmaniasis, and syphilis.

PSAP 2016 Book 2 • GI/Fluids and Nutrition 7 Selected Infections of the GI Tract and Liver

Burgos Chapter by JYT.indd 7 4/21/2016 3:04:16 PM Fungal Infections candidiasis, oropharyngeal and esophageal candidiasis in Considered potential normal flora of the GI tract, Candida patients with HIV infection remain most common when CD4+ spp. are opportunistic pathogens in susceptible hosts such T-lymphocyte counts are less than 200 cells/mm3. as those with immunocompromise. Candida albicans is most Treatment options for mucosal candidiasis are shown in commonly isolated, followed by C. glabrata and C. krusei. Table 1-1. For mild oropharyngeal candidiasis (asymptomatic Risk factors for oropharyngeal and esophageal candidiasis or mild symptoms), treatment with topical agents is consid- include dentures in older adults, recent antibiotics, radiation ered as effective as oral systemic therapy. Topical agents also reduce drug-drug interactions, systemic adverse reac- and/or chemotherapy of head and neck, immune deficiency, tions, and the potential for antifungal resistance. However, and inhaled steroids. Although the availability of effective their unpleasant taste and need for frequent dosing, as with antiretroviral therapy has led to a decreased incidence of clotrimazole and nystatin, and lack of efficacy in esophageal disease are significant disadvantages. When appropriate oral mucosal contact cannot be ensured with topical agents, or BASELINE KNOWLEDGE STATEMENTS when systemic therapy is warranted, oral fluconazole is the drug of choice for oropharyngeal disease because of its equal Readers of this chapter are presumed to be familiar with the following: or improved effectiveness, convenience, and better tolerabil- • Basic knowledge of GI tract anatomy ity. Pregnant women should always be given topical therapy, if possible. • Basic microbiology of common viruses, bacteria, fungi, and parasites Esophageal disease always requires systemic therapy, and • Pharmacology of antimicrobials used for GI tract all major U.S. and European guidelines recommend fluco- infections, including dosing, mechanism of action, nazole as the preferred agent (Lortholary 2012). Oropharyngeal drug interactions, and adverse effects candidiasis with dysphagia or odynophagia usually predicts • Published guidelines on infections of the GI tract esophageal candidiasis, and a therapeutic and diagnostic trial with systemic fluconazole is recommended as a cost-ef- Table of common laboratory reference values fective alternative to endoscopy. If signs and symptoms of disease persist beyond 7–14 days of appropriate antifungal therapy, however, confirmatory culture and endoscopy are

ADDITIONAL READINGS necessary to rule out causes of refractory disease other than azole resistance. The following free resources are available for readers Alternatives to fluconazole, although less well tolerated, desiring additional background information on this include itraconazole, posaconazole, voriconazole, echino- topic. candins, and amphotericin B. Itraconazole oral solution is • Infectious Diseases Society of America (IDSA), recommended for oropharyngeal and esophageal fluco- CDC, and NIH. Guidelines for the Prevention and nazole-refractory disease. Because of variable absorption, Treatment of Opportunistic Infections in HIV- Infected Adults and Adolescents. 2015. itraconazole oral capsules are considered less effective than oral solution. Posaconazole oral suspension is also • IDSA. Clinical Practice Guideline for the Management of Candidiasis. 2016. efficacious for oropharyngeal and esophageal disease • IDSA and Society for Healthcare Epidemiology of unresponsive to fluconazole. Posaconazole is also better America (SHEA). Clinical Practice Guideline for tolerated and has fewer drug interactions than itraconazole Clostridium difficile Infection in Adults. 2010. and voriconazole. Posaconazole delayed-release tablets • American College of Gastroenterology. Guidelines have more reliable absorption, less stringent food require- for Diagnosis, Treatment, and Prevention of ments, and once-daily dosing compared to oral suspension. Clostridium difficile Infections. 2013. Although there is poor evidence for the use of delayed-release • IDSA and Surgical Infection Society (SIS). tablets for the treatment of esophageal candidiasis, expert Diagnosis and Management of Complicated opinion and U.S. guidelines suggest this extended-release Intra-abdominal Infection in Adults and Children. formulation, given these advantages, could be considered for 2010. esophageal disease. • IDSA, American Society of Health-System Caspofungin, micafungin, and anidulafungin are asso- Pharmacists (ASHP), SIS, and SHEA. Clinical ciated with higher esophageal disease relapse rates than Practice Guidelines for Antimicrobial Prophylaxis in Surgery. 2013. is fluconazole. Furthermore, there is potential for acquired • CDC. Sexually Transmitted Diseases Treatment resistance to echinocandins during therapy with these drugs Guidelines. 2015. (Perlin 2015). Intravenous amphotericin B deoxycholate or lipid formulations are effective for esophageal candidiasis, but nephrotoxicity limits use for this indication.

PSAP 2016 Book 2 • GI/Fluids and Nutrition 8 Selected Infections of the GI Tract and Liver

Burgos Chapter by JYT.indd 8 4/21/2016 3:04:16 PM Most U.S. and European guidelines do not recommend rou- disease include CMV, HSV, varicella-zoster virus, and primary tine primary prophylaxis against Candida mucosal disease. A HIV infection. randomized trial showed that suppressive therapy with flu- Cytomegalovirus disease is usually associated with sig- conazole three times per week resulted in fewer episodes of nificant host immunosuppression, and for patients with oropharyngeal and esophageal candidiasis and other fun- HIV infection, initiating antiretroviral therapy for immune gal invasive infections than with episodic treatment. These restoration is paramount to its management. After colitis, strategies resulted in similar rates of fluconazole-resistant esophagitis is the second most common CMV-related dis- isolates (Goldman 2005). Because of high cost, low mortal- ease in the GI tract. Updated guidelines on CMV treatment ity of the disease, high efficacy of episodic treatment, and from the Infectious Diseases Society of America (IDSA), potential for drug interactions and development of antifun- NIH, and CDC were published in 2015. Recommended ini- gal resistance, chronic suppressive therapy with fluconazole tial CMV esophagitis treatment is intravenous ganciclovir 5 is only recommended for recurrent disease or severe recur- mg/kg every 12 hours, transitioning to valganciclovir 900 mg rences of oropharyngeal or esophageal disease. by mouth every 12 hours when the patient can tolerate oral treatment and there are no concerns for impaired absorp- Viral Esophagitis tion. Total recommended treatment duration is 21–42 days In contrast to the endoscopic appearance of fungal esopha- or until resolution of signs and symptoms. For mild disease gitis (friable plaques that can involve the entire esophagus), in patients with HIV infection who can promptly be initi- viral esophagitis appears as erythematous ulcers of the ated on antiretrovirals, either withholding CMV therapy or esophageal mucosa. Viruses associated with esophageal initiating oral valganciclovir is warranted if the patient can

Table 1 -1. Therapy for Oropharyngeal and Esophageal Candidiasis

Chronic, First-line Suppressive Treatment Alternative Therapy Comments

Oropharyngeal Fluconazole 100–200 Clotrimazole 10 mg troches Only if recurrent Topical agents candidiasis mg PO daily five times daily or severe recommended only Nystatin 100,000 U/mL recurrence: for mild disease suspension 4–6 mL four Treatment length times daily • Fluconazole usually 7–14 days Nystatin 200,000 U pastilles 100–200 mg PO 1–2 pastilles four times daily three times a Miconazole 50 mg buccal week tablet daily or Itraconazole 200 mg oral • Fluconazole 100 solution PO daily mg PO daily Posaconazole 400 mg oral suspension PO BID for 3 days, then 400 mg daily

Esophageal Fluconazole 200–400 Itraconazole 200 mg oral solution Only if recurrent or Treatment length candidiasis mg PO or IV daily PO daily severe recurrence: usually 14–21 days Any echinocandin Posaconazole 400 mg oral • Fluconazole Higher rates of suspension PO BID or 100 mg 100–200 mg esophageal delayed-release tablets 300 mg PO daily candidiasis relapse po daily associated with Voriconazole 200 mg PO or IV BID echinocandins than Amphotericin B deoxycholate with fluconazole 0.6 mg/kg IV daily Amphotericin B lipid formulation 3–4 mg/kg IV daily

BID = twice daily; IV = intravenously; PO = orally. Information from: Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guidelines for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis 2016;62:e1-50.

PSAP 2016 Book 2 • GI/Fluids and Nutrition 9 Selected Infections of the GI Tract and Liver

Burgos Chapter by JYT.indd 9 4/21/2016 3:04:17 PM take oral drugs. Colony-stimulating growth factors can be comparing a toxin-binding polymer, tolevamer, with metro- considered for neutropenic patients to augment immune nidazole and vancomycin showed statistically significant restoration. In patients who cannot tolerate ganciclovir or decreased clinical cure rates for metronidazole (72.7%) than with ganciclovir resistance, intravenous foscarnet 60 mg/kg vancomycin (81.1%) (Johnson 2014). In addition, increased every 8 hours or 90 mg/kg every 12 hours is an alternative. metronidazole treatment failures and resistant isolates have Because ganciclovir and valganciclovir can cause anemia, been reported in the literature. Metronidazole is associated neutropenia, thrombocytopenia, nausea, diarrhea, and kid- with adverse effects such as GI complaints, disulfiram-like ney toxicity, close monitoring is required. Monitoring should reaction with concomitant alcohol, and peripheral neuropathy include CBCs, serum electrolytes, and renal function twice with extended use. Because of increased reported resistance per week. Chronic maintenance therapy for GI disease is typ- and cumulative neurotoxicity, metronidazole is not recom- ically recommended only in the presence of concomitant mended beyond the first C. difficile recurrence. According to retinitis; however, it can be considered in recurrent disease. the 2014 study cited previously, it should likely only be used as an alternative to either oral vancomycin or fidaxomicin for CLOSTRIDIUM DIFFICILE patients with mild disease (Johnson 2014). Oral metronidazole is also inferior to vancomycin for severe C. difficile is the most common cause of infectious diarrhea in CDI. When oral metronidazole 250 mg four times daily was hospitalized patients in the United States and Europe. C. dif- compared with oral vancomycin 125 mg four times daily, cure ficile sporulation allows survival in the environment for long rates were similar for mild disease (98% vancomycin vs. 90% periods. Disease pathogenesis involves ingestion of spores metronidazole) and were superior for vancomycin over metro- into a disrupted gut microbiota, germination in the small intes- nidazole in severe disease (97% vs. 76%) (Zar 2007). The oral tine, and growth of vegetative cells in the colon. C. difficile is vancomycin dose should be 125 mg four times daily for mild, not an invasive organism, but its toxins contribute to mucosal moderate, or severe disease. In a 1989 study that evaluated epithelial damage, pseudomembranous colitis, and subse- response rates in patients with probable or proven C. difficile quent systemic disease that may result in sepsis and death. colitis, vancomycin 125 mg four times daily was as effective Microbiota disruption by systemic antimicrobial exposure as a dose of 500 mg four times daily (Fekety 1989). A more is the leading risk factor for C. difficile infection (CDI). The risk recent retrospective study showed that oral vancomycin dos- is greater with increasing number of agents and duration of ages of 500 mg/day did not differ from dosages higher than exposure. Risk is greater with clindamycin, fluoroquinolones, 500 mg/day with respect to clinical cures when adjusted for and second- or higher-generation cephalosporins than with baseline characteristics (Lam 2013). Although IDSA/SHEA penicillins, macrolides, β-lactamase inhibitors, carbapenems, guidelines recommend oral vancomycin doses of 500 mg vancomycin, and metronidazole; the lowest risk is seen with four times daily for severe, complicated CDI, data supporting aminoglycosides, tetracyclines, trimethoprim, sulfonamides, doses higher than 125 mg four times daily for patients with- and rifampin. Other risk factors for CDI include patient age; out severe-complicated CDI are lacking. prior hospitalization; duration of hospitalization; residence in Fidaxomicin was approved for treatment of C. difficile– a long-term care facility; severity of concurrent, underlying associated diarrhea in 2011 on the strength of two phase III illness; use of gastric acid–reducing agents, particularly pro- trials (Cornely 2012; Louie 2011). These trials compared oral ton pump inhibitors and histamine-2 blockers; and abdominal fidaxomicin 200 mg twice daily with oral vancomycin 125 mg surgery or manipulation of the GI tract, including tube feed- four times daily and found noninferiority of cure rates (87.7%– ing. Antibiotic exposure after an initial episode of C. difficile 88.2% for fidaxomicin vs. 85.8%–86.8% for vancomycin) and disease significantly increases recurrence risk, particularly in recurrence rates. Fidaxomicin protects gut microbiota com- older adults and those who are severely ill. pared with vancomycin and metronidazole, and no significant Treatment recommendations by IDSA and the Society resistance has been reported. Because of high cost, fidaxo- for Healthcare Epidemiology of America (SHEA) and by the micin is not recommended first line for mild disease, and its American College of Gastroenterology (ACG) classify CDI use in severe, complicated disease lacks support in the liter- according to severity of disease and whether it is a first or ature. However, a retrospective study evaluated readmission recurrent episode. Figure 1-1 summarizes IDSA/SHEA and rates and length of stay from recurrences with CDI in patients ACG recommendations for the treatment of CDI, as well as who received initial treatment with either oral fidaxomicin possible alternative treatments. or oral vancomycin (Gallagher 2015). Fewer patients who Metronidazole and vancomycin have been the mainstays received fidaxomicin were readmitted with CDI within 90 days of C. difficile treatment for more than 3 decades because of compared with those who received oral vancomycin (20.4% early studies showing similar efficacy, tolerability, and relapse vs. 41.3%; p=0.027). The cost of readmissions from recurrent rates. However, recent data analyses have shown that metro- CDI was $484,800 for the vancomycin group and $196,200 nidazole is inferior to oral vancomycin for the treatment of CDI. for the fidaxomicin group, with lower estimated per-patient A 2014 prospective randomized, placebo-controlled study losses for the institution in the fidaxomicin group than in the

PSAP 2016 Book 2 • GI/Fluids and Nutrition 10 Selected Infections of the GI Tract and Liver

Burgos Chapter by JYT.indd 10 4/21/2016 3:04:17 PM vancomycin group ($3286 vs. $6333). Smaller studies sug- placebo, rifaximin also had lower rates of recurrent diarrhea gest the utility of fidaxomicin “chasers” or tapering doses as a 20-day “chaser” after standard therapy with vancomycin after initial treatment with vancomycin in recurrent disease or metronidazole in a small randomized study (Garey 2011). (Soriano 2014; Johnson 2009; Johnson 2007). Similar to other rifamycins, development of resistance is Rifaximin had symptom resolution rates similar to oral van- common with rifaximin and limits its use. comycin in a randomized trial of 20 patients with CDI (Boero Fecal microbiota transplantation (FMT) is the fastest, most 1990). When rifaximin was studied as eradication therapy for effective strategy for treating patients with several recur- 14 days after standard treatment with metronidazole, 16 of rences of CDI (Cammarota 2015; Kelly 2014; Youngster 2014; 22 patients who completed treatment were stool negative for van Nood 2013). An open-label, randomized trial of patients C. difficile in an open-label study (Basu 2010). Compared with with recurrent infection compared 20 subjects who received a

Diagnosis of C. difﬁcile infection

Initial episode?

Yes No

First recurrence? Metronidazole 500 mg Evaluate severitya Mild PO TID for 10–14 days

Yes No

Alternative, if necessary Severe, complicated Vancomycin 125 mg PO QID for 10–14 days Severe or fidaxomicin 200 mg PO BID for 10 days if at risk of recurrence

Vancomycin 500 mg PO or NG QID plus Consider fecal microbiota metronidazole 500 mg IV transplantationb q8hr for 10–14 days Avoid metronidazole because of risk of cumulative neurotoxicity

For complete ileus, consider adding rectal Use a tapered and/or pulsed instillation of vancomycin regimen of oral vancomycin

Surgical intervention may be necessary May use a “chaser” after the pulsed or tapered regimenc

Figure 1-1. Recommended treatment and potential alternatives for C. difficile infection. aSeverity classification based on IDSA/SHEA definition: severe = WBC ≥ 15 x 103 cells/mm3 or SCr ≥ 1.5 times the pre-illness value. Severe complicated = hypotension, shock, ileus, or megacolon. bFurther antibiotics should be avoided after infusion of donor stool if this option is chosen. cChasers include rifaximin 400 mg PO BID for 14 days or fidaxomicin 200 mg PO BID for 10 days. BID = twice daily; IV = intravenously; NG = nasogastrically; PO = orally; q = every; QID = four times daily; TID = three times daily. Information from: Cohen SH, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society of Healthcare Epidemiology of American (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol 2010;31:431-55; and Surawicz, CM, Brandt LJ, Binion DG, et al. Guidelines for diagnosis, treatment and prevention of Clostridium difficile infections. Am J Gastroenterol 2013;108:478-98.

PSAP 2016 Book 2 • GI/Fluids and Nutrition 11 Selected Infections of the GI Tract and Liver

Burgos Chapter by JYT.indd 11 4/21/2016 3:04:17 PM 3-day vancomycin regimen followed by one or more fecal C. trachomatis is the most commonly reported sexually microbiota colonoscopy infusions with 19 subjects who transmitted infectious disease in the United States, followed received oral vancomycin treatment for 10 days followed by by N. gonorrhea. Antimicrobial resistance of N. gonorrhea is a 3-week pulsed vancomycin regimen (Cammarota 2015). of particular concern, including resistance to fluoroquino- In the FMT group, 90% had resolution of C. difficile–associ- lones and cefixime. This concern, as well as the theoretical ated diarrhea compared with 26% of the vancomycin-only benefit of using two antimicrobials with different mecha- group (p<0.0001). This confirmed a previous randomized, nisms of action to increase efficacy and hinder resistance, placebo-controlled study showing the superiority of FMT to has prompted the CDC since 2010 to recommend dual ther- standard of care (van Nood 2013). Guidance on stool donor apy with intramuscular ceftriaxone plus either azithromycin selection, preparation, and administration by the NIH and the or doxycycline, even in the absence of a positive chlamydial American Gastroenterological Association Fecal Microbiota test. Although N. gonorrhea resistance to ceftriaxone remains Transplantation Workgroup has been published (Bakken 2011). less than 1% in the United States, the incidence is increasing, and the CDC has declared drug-resistant N. gonorrhea an PROCTOCOLITIS AND PROCTITIS urgent public health threat. CAUSED BY SEXUALLY Current CDC guidelines (2015) recommend presumptive TRANSMITTED DISEASE treatment of sexually transmitted disease in people who Infectious proctitis, proctocolitis, and enteritis can be asso- report receptive anal intercourse and have a presentation ciated with sexual transmission of organisms through direct consistent with acute proctitis, if no anoscopy or Gram stain or indirect contact with rectal mucosal surface. The most is available or when awaiting results from laboratory tests or common sexually transmitted organisms associated with Gram stain obtained during anoscopy. In addition, men who proctitis include Neisseria gonorrhea, Chlamydia trachomatis, have sex with men who also present with bloody discharge Treponema pallidum, and HSV. Causative pathogens for proc- or perianal or mucosal ulcers and who either have a positive tocolitis include Campylobacter spp., Shigella spp., Entamoeba nucleic acid amplification test for C. trachomatis or are HIV histolytica, and lymphogranuloma venereum strains of C. positive should be offered a 3-week course of doxycycline for trachomatis (serotypes L1, L2, and L3). Symptoms include presumptive lymphogranuloma venereum infection; if painful anorectal pain, discharge, and tenesmus. Additional symp- perianal or mucosal ulcers are present, presumptive treat- toms of proctocolitis include diarrhea, abdominal cramps, ment of HSV should be offered as well. Table 1-2 summarizes and colonic inflammation. these recommendations.

Patient Care Scenario A 72-year-old man (height 70 inches, weight 70 kg) is ad- ceftriaxone for 2 days with improvement but no resolution mitted for treatment of cellulitis of the left thigh. His med- of cellulitis. Hospital discharge with oral antibiotics was ical history includes hypertension and diabetes; his home planned yesterday, but he reported 10 stools per day, and C. drugs include lisinopril 20 mg daily, hydrochlorothiazide 25 difficile toxin was positive. He has no other concerns and is mg daily, and glipizide XL 10 mg daily. The patient has a his- hemodynamically stable. His SCr is at his recent baseline of tory of two episodes of mild C. difficile disease (9 months 1.5 mg/dL and WBC is 4 x 103 cells/mm3. The patient is un- ago and 5 months ago) that were treated to resolution with willing to consider FMT. What is the best treatment regimen metronidazole. During the present admission, he received for C. difficile in this patient?

ANSWER This is the second recurrence of C. difficile disease. Although 125 mg twice daily for 7 days, followed by 125 mg daily for FMT is the fastest, most effective therapy for recurrent C. 7 days, followed by 125 mg every 2–3 days for 2–8 weeks. difficile disease, the patient would need to consent to in- Many clinicians would use full-dose oral vancomycin thera- stillation of suitable donor stool. Because of concerns for py throughout the course of antibiotics for cellulitis. Consid- resistance and cumulative neurotoxicity, further metronidazole would be avoided after the first recurrence. Guidelines eration should be given to switching from a third-generation recommend a pulsed or tapered course of oral vancomycin, cephalosporin to a class of antibiotic with less risk of C. dif- such as 125 mg four times daily for 10–14 days, followed by ficile, such as a penicillin, if possible.

1. Cohen SH, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society of Healthcare Epidemiology of American (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol 2010;31:431-55. 2. Surawicz, CM, Brandt LJ, Binion DG, et al. Guidelines for diagnosis, treatment and prevention of Clostridium difficile infections. Am J Gastro- enterol 2013;108:478-98.

PSAP 2016 Book 2 • GI/Fluids and Nutrition 12 Selected Infections of the GI Tract and Liver

Burgos Chapter by JYT.indd 12 4/21/2016 3:04:17 PM The CDC recommends retesting 3 months after treat- evidence of systemic inflammation (increased WBC or CRP); ment of chlamydia or gonorrhea. To reduce transmission or evidence of cholestasis; and biliary dilatation or obstruction reinfection, patients and their partners should abstain from on imaging. sexual contact until both have completed a 7-day treatment Acute cholangitis is classified by severity from grade I and symptoms have resolved. In addition, partners of anyone (mild) to grade III (severe). Grade III acute cholangitis is diag- treated for gonorrhea, chlamydia, or lymphogranuloma vene- nosed when dysfunction of at least one organ system occurs, reum should be evaluated, tested, and treated presumptively defined by the following criteria: requirement for vasopres- if sexual contact occurred within 60 days of symptom onset. sor; altered mental status; Pao2/fraction of inspired oxygen ratio less than 300 mm Hg; oliguria or SCr greater than 2 mg/ BILIARY INFECTIONS dL; INR greater than 1.5 because of hepatic dysfunction; or Guidelines from IDSA for management of complicated platelet count less than 100,000/mm3 suggestive of dissem- intra-abdominal infections were published in 2010, includ- inated intravascular coagulation. Grade II (moderate) acute ing a brief section on biliary infection. These guidelines were cholangitis is a non-severe case in which two or more of the based in part on the previous seminal 2007 Tokyo guidelines following factors are present: abnormal WBC (greater than 12 for acute cholangitis and cholecystitis. The Tokyo guidelines x 103 cells/mm3 or less than 4 x 103 cells/mm3); temperature were updated in 2013 with improved clarity of case severity of 102.2°F (39°C) or higher; age 75 years or older; total biliru- definitions that provide a clear algorithm to select empiric bin of 5 mg/dL or higher; or hypoalbuminemia (less than 0.7 antibiotic coverage (Gomi 2013). times normal). Grade I acute cholangitis is diagnosed when the case does not meet criteria for grade II or III. Acute Cholangitis Antimicrobial therapy is required for acute cholangitis Acute cholangitis is acute inflammation and infection of regardless of severity. Blood cultures should be obtained the bile duct occurring secondary to biliary obstruction. before antibiotic initiation. Moderate to severe cases require Gallstones are the most common etiology, followed by biliary drainage, as do mild cases not responding to antibiotic malignancy or benign stenosis. Patients often present therapy. When bile is drained, it should be cultured. with right upper quadrant abdominal pain, fever, and jaun- The Tokyo 2013 guideline recommendations for both dice. Diagnosis requires the presence of fever or laboratory community-acquired and health care–associated acute

Table 1 -2 . Recommended Treatment of Proctitis and Proctocolitis

Syndrome Common Organisms Involved Treatment

Proctitis (rectal pain, discharge, Neisseria gonorrhea Presumptive with ceftriaxone 250 mg IM one tenesmus) Chlamydia trachomatis time plus doxycycline 100 mg PO BID for 7 days Treponema pallidum HSV

Proctitis with bloody discharge, Above organisms, plus LGV Presumptive with ceftriaxone 250 mg IM one perianal ulcers, or mucosal strains of C. trachomatis time plus doxycycline 100 mg PO BID for ulcers in MSM with positive rectal 21 days Chlamydia or positive for HIV If painful, perianal ulcers present or mucosal ulcers on anoscopy, include HSV treatment

Proctocolitis (proctitis symptoms Campylobacter sp. Same presumptive treatment as for proctitis; with cramps or diarrhea) Shigella sp. treat according to organism when results available Entamoeba histolytica LGV strains of C. trachomatis CMV in immunocompromised

BID = twice daily; CMV = cytomegalovirus; HSV = herpes simplex virus; IM = intramuscularly; LGV = lymphogranuloma venereum; MSM = men who have sex with men; PO = orally. Information from: Workowski KA, Bolan GA. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep 2015; 64:1-137.

PSAP 2016 Book 2 • GI/Fluids and Nutrition 13 Selected Infections of the GI Tract and Liver

Burgos Chapter by JYT.indd 13 4/21/2016 3:04:17 PM cholangitis are listed in Table 1-3. The IDSA defines health associated with onset of dysfunction of at least one organ care–associated cases as occurring in patients more than system, using the same criteria defined earlier for grade III 48 hours after a hospital admission; or in patients from the acute cholangitis. Grade II (moderate) acute cholecystitis is a community with invasive devices, a history of methicillin-re- non-severe case in which one or more of the following factors sistant Staphylococcus aureus, or a recent history (past 12 is present: elevated WBC (greater than 18 x 103 cells/mm3); months) of surgery, hospitalization, dialysis, or long-term palpable and tender right upper quadrant mass; duration of care facility residence. symptoms for more than 72 hours; or marked local inflam- Empiric antibiotic therapy for biliary infection targets mation (gangrenous cholecystitis, pericholecystic abscess, gram-negative enteric bacteria because Escherichia coli and hepatic abscess, biliary peritonitis, emphysematous chole- Klebsiella spp. are the most common causes. For severe com- cystitis). Grade I (mild) acute cholecystitis is diagnosed when munity-acquired cases and all health care–associated cases, the case does not meet criteria for grade II or III. Pseudomonas aeruginosa is a concern. When Pseudomonas is Acute calculous cholecystitis can be complicated by sec- not a concern, IDSA recommends against using an antipseu- ondary infections, usually caused by Enterobacteriaceae or domonal antibiotic if another choice can be made. other enteric gram-negative bacteria. The Tokyo guidelines Local antibiotic susceptibility patterns must guide empiric recommend antibiotics for acute calculous cholecystitis antibiotic choice, as well as recent exposure of the patient meeting the diagnostic criteria given earlier, regardless of to antibiotics and the patient’s history of colonization with severity, followed in most cases by laparoscopic cholecystec- drug-resistant organisms. The IDSA recommends against tomy. An additional dose of antibiotic should be given within using an antibiotic empirically when more than 10%–20% of 60 minutes of the surgical incision. relevant isolates tested are resistant. For example, in some In grade I cases, surgery is typically performed within regions, fluoroquinolones may no longer be a reasonable 72 hours. In other cases, surgery may be delayed until the choice for empiric therapy. The IDSA no longer recommends patient’s condition improves, often with a need for gallblad- ampicillin/sulbactam and clindamycin for abdominal infec- der drainage in the interim. For grade II or III severity, blood tions in North America. If susceptibilities become available cultures should be obtained before antibiotics are initiated, from blood or bile cultures, antibiotic regimens should be and bile should be cultured. de-escalated to minimize toxicities and the risk of promoting For antibiotic recommendations for acute calculous cho- microbial resistance. lecystitis, see Table 1-3. The considerations that guide Both IDSA and the Tokyo 2013 guidelines recommend antibiotic choice are similar to those for acute cholangi- covering obligate anaerobes only when a biliary-enteric anas- tis and are based on severity, association of the case with a tomosis is present. In this case, metronidazole would be added health care history, and presence of biliary-enteric anastomo- if the principal antibiotic lacks anaerobic coverage. Empiric sis. Rare cases of acute cholecystitis unrelated to gallstone vancomycin for Enterococcus spp. is recommended for all obstruction (acute acalculous cholecystitis) require simi- health care–associated biliary infection as well as for grade lar empiric antibiotic coverage, but they should always be III community-acquired biliary infection; vancomycin should treated for obligate anaerobes. also be considered for patients with liver transplantation or Patients with grade I acute cholecystitis should have anti- other immunocompromise. This coverage may be broadened biotics discontinued within 24 hours after cholecystectomy, to linezolid or daptomycin in patients with a history or high according to the Tokyo guidelines. If perforation occurs, or if risk of vancomycin-resistant Enterococcus. Therapy dura- emphysematous changes or necrosis of the gallbladder are tion should be 4–7 days after biliary drainage and removal of found during surgery, antibiotics are extended for 4–7 days obstruction. In patients with gram-positive cocci bacteremia, after surgery. Duration of antibiotic therapy is 4–7 days after a 2-week course of therapy should be considered. cholecystectomy in patients with grade II or III acute cholecystitis. In contrast, IDSA recommends discontinuing antibiotics Acute Calculous Cholecystitis within 24 hours after cholecystectomy in all patients unless Acute cholecystitis is inflammation of the gallbladder, usu- infection outside the gallbladder wall is evident. If gram-pos- ally caused by gallstone obstruction of the cystic duct (acute itive cocci bacteremia is present, a 2-week course of therapy calculous cholecystitis). Patients often present with right should be considered. upper quadrant or epigastric pain and nausea and vomiting. Diagnosis requires the presence of fever or laboratory evidence of systemic inflammation (elevated WBC or CRP); right PROPHYLAXIS AGAINST upper quadrant pain or pain on palpation of the gallbladder; INFECTIONS OF THE GI TRACT and imaging findings characteristic of acute cholecystitis Manipulation of the GI tract can result in postprocedural such as gallbladder wall thickening or pericholecystic fluid. infections because of the high burden of microbes present. Acute cholecystitis is classified by severity similarly to Antibiotic prophylaxis can reduce these infections, but it also acute cholangitis. Grade III (severe) acute cholecystitis is disrupts the microbiome, leading to complications such as

PSAP 2016 Book 2 • GI/Fluids and Nutrition 14 Selected Infections of the GI Tract and Liver

Burgos Chapter by JYT.indd 14 4/21/2016 3:04:17 PM CDI and antibiotic resistance. Careful balance of these consid- Patients with existing infections, those with perforated erations is necessary when selecting antibiotic prophylaxis, viscera, and those with traumatic wounds that are no lon- and pharmacists are often involved in these decisions. ger fresh should receive full treatment courses of antibiotics instead of prophylaxis. Treatment should begin before sur- Abdominal Surgery gery, and an antibiotic dose sufficient for SSI prophylaxis should be given within 60 minutes before incision. General Considerations Antibiotics with rapid clearance, including many of the When the lumen of the GI tract is entered during surgery, β-lactam antibiotics, require redosing during surgery if the antibiotic prophylaxis is recommended to prevent surgical procedure takes longer than twice the antibiotic half-life. site infection (SSI). The American Society of Health-System For example, cefazolin should be redosed every 4 hours Pharmacists/IDSA/Surgical Infection Society/SHEA guide- during surgery, whereas vancomycin requires no redosing. lines for antimicrobial prophylaxis in surgery have been The updated guideline offers a table of suggested redosing updated to reflect several important concepts, including the frequencies. timing of the preoperative dose, redosing during surgery, and For abdominal surgery, antibiotic prophylaxis should con- duration of prophylaxis. tinue no longer than 24 hours after the surgery; in fact, most The preoperative dose should be given such that ade- data suggest that no postoperative doses are required. quate tissue concentration is achieved at the time of surgery. A recent retrospective study of appendectomy for non- Adequate antibiotic concentration in tissue is achieved when perforated appendicitis shows the potential benefits of antibiotics are given even 7–20 minutes before incision, and minimizing antibiotic prophylaxis. Of the 728 cases reviewed, some studies suggest that a preoperative dose within 30 min- 334 patients received postoperative antibiotics and 394 did utes of incision is ideal to prevent SSI. The IDSA guideline not. The authors found no baseline difference between the recommends initiating antibiotic infusion within 60 min- two groups for preoperative morbidity, preoperative antibiot- utes before the first surgical incision. This reflects a change ics, operating room time, blood loss, or appendiceal diameter. from the prior recommendation to administer at induction of There was no statistically significant difference in the inci- anesthesia. Antibiotics with longer infusion times (e.g., van- dence of postoperative SSI. Statistically significant findings comycin, fluoroquinolones) should be initiated within 120 included a 5-fold higher incidence of postoperative diarrhea, minutes before incision. a 5-fold higher incidence of UTI, and a doubling in length of

Table 1 -3. Empiric Antibiotic Regimens for Acute Cholangitis and Acute Calculous Cholecystitis

Community Acquired Health Care Associated

c c Antibiotic Grade I Grade II Grade III Any severity

Cefazolina,b *

Cefoxitinb *

Ceftriaxonea or cefotaximea * *

Ertapenem * *

Ciprofloxacina,b or levofloxacina,b * *

Moxifloxacinb * *

Cefepimea or ceftazidimea * * *

Piperacillin/tazobactam * * *

Imipenem/cilastatin * *

Meropenem or doripenem * *

Aztreonama * * aCoverage for obligate anaerobes using metronidazole should be added if biliary-enteric anastomosis is present because principal antibiotic lacks sufficient anaerobic coverage. bLocal antimicrobial susceptibility patterns should be considered for empiric use. cAdd vancomycin for community-acquired grade III and health care–associated infections. Adapted from: Gomi H, Solomkin JS, Takada T, et al. TG13 antimicrobial therapy for acute cholangitis and cholecystitis. J Hepatobiliary Pancreat Sci 2013;20:60-70.

PSAP 2016 Book 2 • GI/Fluids and Nutrition 15 Selected Infections of the GI Tract and Liver

Burgos Chapter by JYT.indd 15 4/21/2016 3:04:17 PM stay in the group that received any postoperative antibiotic Transarterial chemoembolization is the preferred therapy compared with the group that did not. No CDI was found in the for treatment of intermediate-stage nonresectable hepato- group that did not receive postoperative antibiotics, whereas cellular carcinoma in patients whose liver function remains 1.5% of patients who did receive postoperative antibiotics sufficient. The incidence of liver abscess after TACE has been developed CDI (p=0.02) (Coakley 2011). reported as 2%, but patients with intact biliary systems have In elective, laparoscopic cholecystectomy in patients abscess rates of less than 1% after TACE. considered at low risk of SSI, the recommendation is for Two similar-sized randomized controlled trials showed a no antibiotic prophylaxis. High-risk factors include emer- survival benefit for TACE compared with supportive care of gency procedure, acute cholecystitis, diabetes, anticipated hepatocellular carcinoma. One trial used antibiotic prophy- procedure duration of more than 120 minutes, risk of intra- laxis before and for 3 days after TACE, whereas the other used operative gallbladder rupture, age older than 70 years, risk of no antibiotics. Both trials produced similar reductions in mor- conversion from laparoscopic to open procedure, American tality of about 50%, and only one liver abscess was reported Society of Anesthesiologists physical status classification (Llovet 2002; Lo 2002). Few studies have assessed whether of 3 or higher, episode of biliary colic within 30 days prior, prophylactic antibiotics are beneficial in preventing abscess reintervention for noninfectious complications of a biliary formation after locoregional therapy, and none has shown a operation done in the prior 30 days, anticipated bile spill- benefit of prophylactic antibiotics in a general population. age, jaundice, pregnancy, nonfunctioning gallbladder, and Current guidelines suggest no routine antibiotic prophylaxis immunosuppression. before or after locoregional therapy (Bruix 2011). Most abscess formation after locoregional therapy for liver Antibiotic Selection tumors occurs in patients who have undergone prior biliary Antibiotic choice for prophylaxis is governed by surgical site procedures such as surgery, stenting, or sphincterotomy. Two and the flora implicated in potential SSI at that site. As with studies showed a failure of first-generation cephalosporins all surgery, skin flora are often implicated. If the GI tract is with or without metronidazole to prevent abscess formation entered, SSI is commonly caused by enteric organisms, espe- in these patients (Geschwind 2002; Kim 2001). Guidelines do cially the gram-negative organisms E. coli and Klebsiella spp. not specifically address these high-risk patients. For these Appendectomy, surgery of obstructed small intestine, and patients, it is reasonable to follow the procedure documented colorectal surgery are associated with SSI caused by obligate in two small studies in which bowel decontamination coupled anaerobes such as Bacteroides fragilis. with broad-spectrum antibiotics resulted in case series with Cefazolin is therefore recommended as prophylaxis for fewer abscesses than historical rates (Patel 2006; Geschwind gastroduodenal surgery, percutaneous endoscopic gastros- 2002). The regimens used were a neomycin-based bowel tomy tube placement, open and laparoscopic biliary tract preparation three times on the day before TACE; plus either surgery, and surgery of the small intestine when no obstruc- piperacillin/tazobactam given for 3 days, starting about tion is present. Cefazolin plus metronidazole is recommended 24 hours before TACE, or levofloxacin plus metronidazole, for surgery of the small intestine when obstruction is present, started 2 days before TACE and continued for 2 weeks after for appendectomy, and for colorectal surgery, with cefoxitin TACE. It is unclear whether the preprocedure antibiotic bowel or cefotetan as alternatives. For colorectal surgery, adding an preparation is necessary, and the optimal duration of sys- oral antibiotic such as neomycin to mechanical bowel prepa- temic antibiotics after the procedure is unknown. ration on the day before surgery further reduced SSI in some Postembolization syndrome including fever and pain studies. is expected after locoregional therapy for liver tumors as a Prophylaxis for patients with true allergy to β-lac- result of tissue necrosis; therefore, a fever lasting 48 hours tam antibiotics must cover the most common organisms. postprocedure is not reason for concern. Persistent fever, Clindamycin or vancomycin, each paired with an aminoglyco- especially in the setting of increased WBC, should prompt side, aztreonam, or a fluoroquinolone, is the recommended investigation for infection, including liver abscess. regimen for gastroduodenal and biliary surgery. Clindamycin or metronidazole, each paired with an aminoglycoside or a Endoscopic Retrograde fluoroquinolone, is the recommended regimen for colorectal Cholangiopancreatography surgery and appendectomy. Endoscopic retrograde cholangiopancreatography (ERCP) is a common procedure to visualize and intervene on biliary Locoregional Therapy for Liver Tumors and pancreatic ducts. Infectious complications after ERCP Locoregional therapies for hepatocellular carcinoma and have been reported to occur in 0.5%–3% of cases. Most infec- hepatic metastases induce tissue ischemia and necrosis and tions occur after procedures in which biliary drainage was carry a risk of liver abscess. These procedures include tran- incomplete. sarterial embolization with or without chemoembolization Past recommendations for antibiotic prophylaxis for ERCP (TACE, TAE), radiofrequency ablation, and chemical ablation. were based in part on an assumption that prophylaxis against

PSAP 2016 Book 2 • GI/Fluids and Nutrition 16 Selected Infections of the GI Tract and Liver

Burgos Chapter by JYT.indd 16 4/21/2016 3:04:17 PM infective endocarditis was needed for ERCP; this is no longer Duodenoscopes used for ERCP are complex instruments; accepted in the latest British and North American GI endos- they have small moving parts and channels and are difficult copy guidelines after a change in guidance from the American to decontaminate. One hospital with a carbapenem-resistant Heart Association (Khashab 2015; Allison 2009). Enterobacteriaceae outbreak linked to ERCP has undertaken The American Society for Gastrointestinal Endoscopy now a program of culturing all duodenoscopes after standard dis- states that routine antibiotic prophylaxis is not necessary infection, followed by quarantine. During a 1-year period, 1.9% for patients without biliary obstruction or for whom com- of the duodenoscope cultures were positive for pathogens, plete biliary drainage during the ERCP procedure is expected requiring further decontamination of the endoscopes before (Khashab 2015). Patients for whom incomplete biliary drain- reuse (Ross 2015). age is anticipated should receive a dose of antibiotic before The FDA continues to recommend ERCP with thorough the ERCP procedure. Other patients for whom pre-ERCP anti- cleaning and disinfection of duodenoscopes according to biotic prophylaxis is recommended include patients who are manufacturer instructions between uses. Duodenoscopes post-liver transplantation, patients with an absolute neutro- suspected of transmitting infection should be decontami- phil count less than 500 cells/mm3, patients with advanced nated and verified to be free of pathogens. An FDA advisory panel convened in 2015 to consider whether further mea- hematologic malignancy, and patients with pancreatic cyst or sures such as sterilization or instrument redesign should be pseudocyst. The antibiotic should cover enteric gram-nega- required, but no final decision was reached. Patients should tive bacteria. Fluoroquinolones such as oral ciprofloxacin 750 report fever, chills, chest pain, severe abdominal pain, trou- mg are recommended (Allison 2009). ble swallowing or breathing, nausea and vomiting, or black or One quality improvement project limited prophylactic tarry stools after ERCP. Antibiotic therapy, when post-ERCP antibiotic use for ERCP to patients with predicted incom- infections are diagnosed, should be guided by culture results, plete drainage or immunosuppression. The authors showed when possible. Infections possibly related to duodenoscopes a reduction in pre-ERCP antibiotic use from 95% to 26% of should be reported to the manufacturer and to the FDA. all ERCP procedures. The infection rate was 0.48% before the change and 0.23% after (Cotton 2008). A 2010 Cochrane SELECTED PARASITIC INFECTION review found reduced risk of bacteremia and cholangitis OF THE INTESTINE AND LIVER when prophylactic antibiotics were used before ERCP, but no reduction in mortality (Brand 2010). When the analysis was Invasive Amoebiasis limited to patients with complete biliary drainage, there was E. histolytica is the second leading cause of death from par- no significant benefit of antibiotic prophylaxis for reducing asitic disease worldwide. This protozoan is common in the cholangitis. Another meta-analysis showed no benefit of pro- developing world, including South and Southeast Asia, the phylactic antibiotics for preventing post-ERCP cholangitis or Middle East, and Central and South America. Travelers to and septicemia overall (Bai 2009). immigrants from these areas may become colonized with or Any patient for whom complete biliary drainage is not infected with E. histolytica. In the United States, most cases achieved should receive a course of post-ERCP antibiot- are reported in the Southwest states among Hispanics. ics. The therapy duration is not well defined, but usually it is Invasion of the intestinal lining by E. histolytica typically until definitive therapy for the obstruction is accomplished. causes dysentery. The most common extraintestinal man- Patients with suspected cholangitis at the time of ERCP ifestation is liver abscess, which develops in about 1% of should be established on an empiric antibiotic course before patients with clinically active disease, is 10 times more common in men than in women, and may occur months to years the ERCP procedure; an additional single dose just before after exposure. Liver abscess typically presents with fever, ERCP is not recommended. right upper quadrant abdominal pain, hepatomegaly, and leu- Quality Improvement: Infection Secondary kocytosis. Imaging reveals a single abscess or coalescing to Contaminated Duodenoscopes multiple abscesses, often in the right lobe. Stool antigen is More than 500,000 ERCP procedures are performed in the often negative, whereas serum antigen and serum anti-amoe- United States each year. Increased surveillance for multi- bic antibodies are often positive. Untreated, amoebic liver drug-resistant pathogens including carbapenem-resistant abscess is fatal. Enterobacteriaceae has shown outbreaks of drug-resis- Short courses of metronidazole or tinidazole are sufficient tant infections linked to ERCP. The FDA received medical for invasive disease such as amoebic colitis and liver abscess device reports regarding 135 patients with possible micro- (Haque 2003) (Table 1-4). Abscess drainage is rarely neces- bial transmission by duodenoscopes during 2013 and 2014. sary but may be necessitated by bacterial coinfection. After Several outbreaks have been reported in the literature as well. completing therapy for invasive disease, the patient should Infection sites have included bile, blood, abdominal fluid, pan- receive the luminal agent paromomycin to eliminate intestinal colonization. Close contacts of the infected person may creatic fluid, urine, lung, and wounds.

PSAP 2016 Book 2 • GI/Fluids and Nutrition 17 Selected Infections of the GI Tract and Liver

Burgos Chapter by JYT.indd 17 4/21/2016 3:04:17 PM be carriers. Asymptomatic carriers should be treated with worms usually requires microscopic observation of eggs in paromomycin because colonization can progress to invasive the stool. Eosinophilia also suggests helminth infection. disease, and carriers shed infectious cysts. Treatment of pinworm and hookworm consists of albendazole or pyrantel pamoate (see Table 1-4). Regimens using Intestinal Worms mebendazole are commonly cited in the literature, but this drug was withdrawn from commercial production in the North America United States in 2011 and is now only available from com- In the United States, the most common parasitic nematodes pounding pharmacies. are the pinworm (Enterobius vermicularis) and the hookworm (Necator americanus). Pinworms live in the cecum, Intestinal Parasites in Refugee Populations and females lay thousands of eggs on the host’s perineum Thousands of other parasitic helminths have been identi- at night, causing itching. The eggs are spread by the fecal- fied, and hundreds are associated with disease throughout oral route, and children are significant hosts. Pinworms are the developing world. A recent review limited to fishborne largely innocuous, but restlessness at night in children may flukes identified almost 60 species that infect humans world- be a sign of infection. Hookworm infections are less common wide. The global burden of GI helminth infection has been but more serious. Transmission is through skin contact with estimated at more than 1 billion people. Some governments soil contaminated by infected feces. Consumption of blood have instituted mass drug administration programs against by hookworms attached to the small intestine may result in common parasites, but for many organisms, the rate of host anemia, pica, and wasting. Definitive diagnosis of intestinal reinfection is high.

Table 1-4. Oral Drug Therapy for Parasitic Infections

Antiparasitic Agent Parasite Treated Adult Dosing Duration Additional Notes

Metronidazole Entamoeba histolytica 500–750 mg TID 7–10 days A luminal agent should also be invasive infection used, after therapy for invasive Tinidazole 2 g/day 3 days disease (3–5 days for abscess)

Paromomycin E. histolytica luminal 25–35 mg/kg/day 7 days For asymptomatic carriers or after colonization divided TID therapy for invasive disease

Albendazole Enterobius 400 mg one time May repeat in 2 weeks if Take with a fatty meal vermicularis persistent (pinworm)

Necator americanus 400 mg one time Confirm clearance after 2 weeks (hookworm) Use supplemental iron

Echinococcus spp. 15 mg/kg/day divided Often long term Monthly treatment interruptions BID (maximum 800 mg/ are no longer recommended day)

Presumptive 400 mg one time See CDC guidelines for which treatment of refugees refugees to treat, including advice for soil helminths on pregnancy and children

Pyrantel pamoate E. vermicularis 11 mg/kg one time May repeat in 2 weeks if (pinworm) (maximum 1 g/dose) persistent

N. americanus 11 mg/kg once daily 3 days Confirm clearance after 2 weeks (hookworm) (maximum 1 g/dose) Use supplemental iron

Praziquantel Clonorchis sinensis, 75 mg/kg/day divided 2 days Take with liquids during meals Opisthorchis spp. TID

Triclabendazole Fasciola hepatica 10 mg/kg one time May repeat in 12 hours Take with food for severe infection Available from CDC as an Investigational New Drug

BID = twice daily; TID = three times daily.

PSAP 2016 Book 2 • GI/Fluids and Nutrition 18 Selected Infections of the GI Tract and Liver

Burgos Chapter by JYT.indd 18 4/21/2016 3:04:18 PM Given the high burden of intestinal parasites worldwide, (Brunetti 2010). Where available, mebendazole is an option the CDC recommends presumptive treatment of refugees. for patients who cannot tolerate albendazole. Ideally, drug The program was started in 1999 with a recommendation for therapy is paired with a surgical or aspiration procedure for single-dose albendazole for refugees from the developing AE and all but certain of the smallest CE lesions. If surgery or world (see Table 1-4). In the past 10 years, recommenda- aspiration is performed for CE, the first dose of drug should tions for praziquantel (for Schistosoma) and ivermectin (for be given before the procedure. For CE, drug therapy is typi- Strongyloides) have been added for certain groups. Since the cally continued for 1 month after surgery or aspiration, or for start of the CDC program, the prevalence of intestinal para- at least 3–6 months if CE is treated only with drugs. For AE, site infection of refugees arriving in the United States has drug therapy is continued for 2 years in those with complete dropped considerably. Ascaris, hookworm, and Strongyloides resection of the lesion and lifelong in all other cases. each have a prevalence below 1%. For any nematode infec- Monitoring of albendazole sulfoxide concentration is rec- tion, the prevalence has fallen from more than 20% to less ommended at 1, 4, and 12 weeks after therapy initiation. than 5% (Swanson 2012). Albendazole sulfoxide blood concentration 4 hours after the The recommended combination therapy is updated period- morning dose should be 0.65–3 micromoles/L. Monitoring ically and varies greatly by country of origin; therefore, those for leukopenia, thrombocytopenia, and hepatotoxicity is encountering refugees should consult the guidelines for recommended every 2 weeks for the first 3 months of alben- overseas management of departing refugees and domestic dazole therapy, then monthly for the first year, then every 3 management of arriving refugees directly on the CDC website. months. A decrease in WBC to less than 1 x 103 cells/mm3 Care must be taken in small children and pregnant women. For merits treatment cessation. If transaminases increase above a detailed discussion of risk-benefit of antihelminthic drugs 5 times the upper limit of normal, it is recommended to check in pregnancy and childhood, see the WHO manual on preven- drug concentration. tive chemotherapy for human helminthiases in addition to the Drug cost can be a limiting factor in the developing world; CDC websites. Clinicians who encounter rare parasitic infec- therefore, drug-minimizing regimens have been described in tions should also be aware of the CDC Drug Service, which consensus statements, but these are not ideal. Cost is a grow- provides selected drugs by Investigational New Drug applica- ing issue in developed nations as well, especially for patients tion, and the CDC’s Parasitic Diseases Hotline (404-718-4745). requiring prolonged courses of therapy. In the United States, the only commercial manufacturer of mebendazole stopped Liver Disease Associated with Helminths production in 2011. Between 2010 and 2013, the listed aver- Several helminths are strongly linked to liver disease, includ- age wholesale price for generic albendazole increased more ing Echinococcus and the liver flukes. The time from infection than 1900% (Alpern 2014). The drug manufacturer offers a to clinical presentation is often prolonged, and therefore patient assistance program, and refugees may qualify for the these infections may be encountered in immigrants and Refugee Medical Assistance Program. returning travelers. Liver Flukes Echinococcosis Liver flukes includeFasciola hepatica, which is endemic in live- The liver is the principal organ affected by the tapeworms stock farming areas worldwide; Clonorchis sinensis, which is Echinococcus granulosus and E. multilocularis. The former prevalent in Asia and especially China; and Opisthorchis spp., causes cystic echinococcosis (CE), also known as hydatid which are common in Asia and Eastern Europe. Infection is cyst disease, which usually involves a solitary cyst in the food- or waterborne. Serious complications of infection can liver; E. multilocularis causes alveolar echinococcosis (AE), present years after initial exposure because Fasciola may usually involving metacestodes in the liver that may metas- have a 10-year life span and Opisthorchis can live dozens of tasize to other organs. Areas with high endemicity are the years. livestock farming areas of South America, Eurasia, the Adult C. sinensis and Opisthorchis worms, which live in the Middle East, and East Africa for CE and the rural areas of the intrahepatic bile ducts, have been implicated in pigmented Northern Hemisphere for AE. Both forms, but especially AE, bile stone formation. The worms themselves cause biliary may require many years after exposure to manifest clinically. obstruction and resulting complications (e.g., cholangitis, Diagnosis is based on clinical presentation, travel history, cholecystitis, abscess, peritonitis, pancreatitis). These liver diagnostic imaging, serologies, PCR, and visualization of par- flukes have been strongly implicated as a risk factor for chol- asites. Bacterial superinfection can occur. Without adequate angiocarcinoma, and the International Agency for Research treatment, both forms can be fatal, but untreated AE carries on Cancer classifiesO. viverrini and C. sinensis as group 1 car- an especially poor prognosis. cinogens. Praziquantel is the recommended treatment (see Drug therapy with albendazole (see Table 1-4) is recom- Table 1-4), and an ERCP will be needed in cases of obstruction. mended in all CE and AE cases, except for CE that is classified F. hepatica undergoes both an acute hepatic and a as “inactive,” according to the WHO classification system chronic biliary phase of infection. Biliary infection can cause

PSAP 2016 Book 2 • GI/Fluids and Nutrition 19 Selected Infections of the GI Tract and Liver

Burgos Chapter by JYT.indd 19 4/21/2016 3:04:18 PM obstruction and its resulting complications. The presenta- Brunetti E, Kern P, Vuitton DA; Writing Panel for the WHO- tion may be intermittent. Praziquantel is not effective for F. IWGE. Expert consensus for the diagnosis and treatment hepatica. The drug of choice is triclabendazole (see Table of cystic and alveolar echinococcosis in humans. Acta Trop 2010;114:1-16. 1-4), which is not commercially available in the United States but is available through the CDC. When triclabendazole can- Cammarota G, Masucci L, Ianiro G, et al. Randomised clinical not be obtained, nitazoxanide is an option. An ERCP should trial: faecal microbiota transplantation by colonoscopy vs. be performed for biliary fascioliasis because ERCP allows vancomycin for the treatment of recurrent Clostridium difficile infection. Aliment Pharmacol Ther 2015;41:835-43. extraction of the worm and biliary drainage. Coakley BA, Sussman ES, Wolfson TS, et al. Postoperative CONCLUSION antibiotics correlate with worse outcomes after appendectomy for nonperforated appendicitis. J Am Coll Surg The GI tract and hepatobiliary system are vulnerable to 2011;213:778-83. infection caused by viruses, bacteria, fungi, and parasites. Pharmacologic therapy is often essential. Correct identifi- Cornely OA, Crook DW, Esposito R, et al; OPT-80-004 Clinical cation of the infection is key to selecting an empiric therapy Study Group. Fidaxomicin versus vancomycin for infection with Clostridium difficile in Europe, Canada, and the USA: a likely to be effective. Therapy choice is often guided by the double-blind, non-inferiority, randomised controlled trial. presenting clinical picture, diagnostic imaging, serology, and Lancet Infect Dis 2012;12:281-9. cultures of blood, tissue, or fluid. Pharmacists play a role in selecting optimal empiric therapy, determining treatment Cotton PB, Connor P, Rawls E, et al. Infection after ERCP, and antibiotic prophylaxis: a sequential quality-im- duration, tailoring antimicrobial therapy to susceptibility provement approach over 11 years. Gastrointest Endosc results, monitoring for adverse effects, and helping ensure 2008;67:471-5. access to drugs. Fekety R, Silva J, Kauffman C, et al. Treatment of antibiotic-associated Clostridium difficile colitis with oral REFERENCES vancomycin: comparison of two dosage regimens. Am J Allison MC, Sandoe JA, Tighe R, et al; Endoscopy Med 1989;86:15-9. Committee of the British Society of Gastroenterology. Antibiotic prophylaxis in gastrointestinal endoscopy. Gut Gallagher JC, Reilly JP, Navalkele B, et al. Clinical and eco- 2009;58:869-80. nomic benefits of fidaxomicin compared to vancomycin for Clostridium difficile infection. Antimicrob Agents Alpern JD, Stauffer WM, Kesselheim AS. High-cost generic Chemother 2015;59:7007-10. drugs – implications for patients and policymakers. N Engl J Med 2014;371:1859-62. Garey KW, Ghantoji SS, Shah DN, et al. A randomized, double-blind, placebo-controlled pilot study to assess the Bai Y, Gao F, Gao J, et al. Prophylactic antibiotics cannot ability of rifaximin to prevent recurrent diarrhoea in prevent endoscopic retrograde cholangiopancreatog- patients with Clostridium difficile infection. J Antimicrob raphy-induced cholangitis: a meta-analysis. Pancreas Chemother 2011;66:2850-5. 2009;38:126-30. Geschwind JF, Kaushik S, Ramsey DE, et al. Influence of a Bakken JS, Borody T, Brandt LJ, et al. Treating Clostridium dif- new prophylactic antibiotic therapy on the incidence of ficile infection with fecal microbiota transplantation. Clin liver abscesses after chemoembolization treatment of Gastroenterol Hepatol 2011;9:1044-9. liver tumors. J Vasc Interv Radiol 2002;13:1163-6.

Basu P, Dinani A, Rayapudi K, et al. Rifaximin therapy for Goldman M, Cloud GA, Wade KD, et al. A randomized study of metronidazole-unresponsive Clostridium difficile infec- the use of fluconazole in continuous versus episodic ther- tion: a prospective pilot trial. Therap Adv Gastroenterol apy in patients with advanced HIV infection and a history 2010;3:221-5. of oropharyngeal candidiasis: AIDS Clinical Trials Group Study 323/Mycoses Study Group Study 40. Clin Infect Dis Boero M, Berti E, Morgando A, et al. Treatment for colitis 2005;41:1473-80. caused by Clostridium difficile: results of a randomized open study of rifaximin vs. vancomycin. Microbiol Med Gomi H, Solomkin JS, Takada T, et al; Tokyo Guideline (Milan) 1990;5:74-7. Revision Committee. TG13 antimicrobial therapy for acute cholangitis and cholecystitis. J Hepatobiliary Pancreat Sci Brand M, Bizos D, O’Farrell P Jr. Antibiotic prophylaxis for 2013;20:60-70. patients undergoing elective endoscopic retrograde cholangiopancreatography. Cochrane Database Syst Rev Haque R, Huston CD, Hughes M, et al. Amebiasis. N Engl J 2010;10:CD007345. Med 2003;348:1565-73.

Bruix J, Sherman M; American Association for the Study of Johnson S, Louie TJ, Gerding DN, et al; Polymer Alternative Liver Diseases. Management of hepatocellular carcinoma: for CDI Treatment (PACT) investigators. Vancomycin, met- an update. Hepatology 2011;53:1020-2. ronidazole, or tolevamer for Clostridium difficile infection:

PSAP 2016 Book 2 • GI/Fluids and Nutrition 20 Selected Infections of the GI Tract and Liver

Burgos Chapter by JYT.indd 20 4/21/2016 3:04:18 PM results from two multinational, randomized, controlled tri- refractory to standard therapies. Open Forum Infect Dis als. Clin Infect Dis 2014;59:345-54. 2014;1:1-7.

Johnson S, Schriever C, Galang M, et al. Interruption of recur- Swanson SJ, Phares CR, Mamo B, et al. Albendazole therapy rent Clostridium difficile-associated diarrhea episodes by and enteric parasites in United States-bound refugees. N serial therapy with vancomycin and rifaximin. Clin Infect Engl J Med 2012;366:1498-507. Dis 2007;44:846-8. van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal infusion Johnson S, Schriever C, Patel U, et al. Rifaximin redux: of donor feces for recurrent Clostridium difficile. N Engl J treatment of recurrent Clostridium difficile infections Med 2013;368:407-15. with rifaximin immediately post-vancomycin treatment. Anaerobe 2009;15:290-1. Youngster I, Russell GH, Pindar C, et al. Oral, capsulized, frozen fecal microbiota transplantation for relapsing Kelly CR, Ihunnah C, Fischer M, et al. Fecal microbiota Clostridium difficile infection. JAMA 2014;312:1772-8. transplant for treatment of Clostridium difficile infection in immunocompromised patients. Am J Gastroenterol Zar FA, Bakkanagari SR, Moorthi KM, et al. A comparison 2014;109:1065-71. of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea, stratified by dis- Khashab MA, Chithadi KV, Acosta RD, et al; ASGE Standards ease severity. Clin Infect Dis 2007;45:302-7. of Practice Committee. Antibiotic prophylaxis for GI endoscopy. Gastrointest Endosc 2015;81:81-9.

Kim W, Clark TW, Baum RA, et al. Risk factors for liver abscess formation after hepatic chemoembolization. J Vasc Interv Radiol 2001;12:965-8.

Lam SW, Bass SN, Neuner EA, et al. Effect of vancomycin dose on treatment outcomes in severe Clostridium difficile infection. Int J Antimicrob Agents 2013;42:553-8.

Llovet JM, Real MI, Montaña X, et al; Barcelona Liver Cancer Group. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet 2002;359:1734-9.

Lo CM, Ngan H, Tso WK, et al. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology 2002;35:1164-71.

Lortholary O, Petrikkos G, Akova M, et al; ESCMID Fungal Infection Study Group. ESCMID guideline for the diagnosis and management of Candida diseases 2012: patients with HIV infection or AIDS. Clin Microbiol Infect 2012;18(suppl 7):68-77.

Louie TJ, Miller MA, Mullane KM, et al; OPT-80- 003 Clinical Study Group. Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med 2011;364:422-31.

Patel S, Tuite CM, Mondschein JI, et al. Effectiveness of an aggressive antibiotic regimen for chemoembolization in patients with previous biliary intervention. J Vasc Interv Radiol 2006;17:1931-4.

Perlin DS. Echinocandin resistance in Candida. Clin Infect Dis 2015;61(suppl 6):s612-7.

Ross AS, Baliga C, Verma P, et al. A quarantine process for the resolution of duodenoscope-associated transmission of multidrug-resistant Escherichia coli. Gastrointest Endosc 2015;82:477-83.

Soriano MM, Danziger LH, Gerding DN, et al. Novel fidaxomicin treatment regimens for patients with multiple Clostridium difficile infection recurrences that are

PSAP 2016 Book 2 • GI/Fluids and Nutrition 21 Selected Infections of the GI Tract and Liver

Burgos Chapter by JYT.indd 21 4/21/2016 3:04:18 PM Self-Assessment Questions

Questions 1 and 2 pertain to the following case. 3. A patient with esophagitis secondary to CMV is trans- F.H. is a 47-year-old woman with a history of HIV/AIDS (diag- ferred to a skilled nursing facility to continue intravenous nosed 15 years ago), cryptosporidiosis at the time of HIV ganciclovir therapy initiated in the hospital 1 week ago. diagnosis, onychomycosis of toenails (6 years ago), com- The patient’s odynophagia has resolved. The skilled munity-acquired pneumonia (3 years ago), and recurrent nursing facility contacts you because no orders were oropharyngeal and esophageal candidiasis, which was suc- sent with the patient. The patient has a clinic appoint- cessfully treated with fluconazole five times in the past 2 ment in 2 weeks. Which one of the following is best to years. She has poor adherence to her HIV antiretrovirals recommend for this patient? because of major depression and social issues. Her CD4+ A. Continue intravenous ganciclovir and monitor CBCs is 5 cells/mm3 (1%) and HIV RNA is 145,546 copies/mL. Her and liver function once per week. antiretrovirals include tenofovir/emtricitabine and cobi- B. Continue intravenous ganciclovir and monitor renal cistat-boosted darunavir. F.H. reports 1 week of painful function, CBC, and serum electrolytes twice per swallowing but states she has been able to eat, although with week. some pain and discomfort. The physician reports oropharyn- C. Discontinue intravenous ganciclovir and initiate oral geal thrush on examination. valganciclovir without laboratory monitoring until 1. Which one of the following 2-week courses of therapy is the follow-up appointment. best to recommend for F.H.? D. Discontinue intravenous ganciclovir and initiate oral A. Fluconazole tablet, 200 mg by mouth once daily valganciclovir while monitoring renal function, CBC, B. Itraconazole capsule, 200 mg by mouth once daily and serum electrolytes twice per week. C. Nystatin oral suspension, swish and swallow four times daily Questions 4 and 5 pertain to the following case. D. Voriconazole tablet, 200 mg by mouth twice daily R.D. is a 60-year-old man who resides in a nursing home. He has a history of recurrent hospitalizations and many medi- 2. F.H.’s oropharyngeal thrush resolved after 2 weeks of cal problems, including three episodes of Clostridium difficile antifungal therapy, but she presents to the ED with con- diarrhea in the past 90 days. One episode was treated with tinuing odynophagia, failure to thrive, and dehydration metronidazole and two episodes were treated with oral van- because she cannot swallow. Endoscopy reveals ery- comycin, including a vancomycin taper. Three weeks ago, thematous ulcers of the esophagus consistent with R.D. was admitted to the hospital with a periorbital abscess, cytomegalovirus (CMV) disease, with biopsy results which was treated with clindamycin. He then developed a pending. Plasma CMV PCR is 754,675 copies/mL (range fourth episode of diarrhea positive for C. difficile toxin. He has 450–5,500,000 copies/mL). Her eye examination is now completed the course of clindamycin as well as a 2-week within normal limits. Which one of the following is best treatment with oral vancomycin 125 mg by mouth four times to recommend for F.H.? daily with marked improvement in his diarrhea, but without A. Initiate intravenous caspofungin for a total of 2–3 complete resolution. weeks of treatment with symptom resolution. B. Initiate intravenous ganciclovir and transition to 4. Which one of the following is best to recommend for valganciclovir when she can tolerate oral treatment R.D.? for a total of 3–6 weeks of treatment with symptom A. No further treatment resolution. B. Fecal microbiota transplantation C. Initiate intravenous ganciclovir and transition to C. Oral metronidazole “chaser” valganciclovir when she can tolerate oral treatment D. Oral vancomycin taper for a total of 3–6 weeks of treatment; then institute once-daily valganciclovir maintenance until immune reconstitution with HIV antiretroviral therapy. D. Initiated intravenous foscarnet for a total treatment of 3–6 weeks with symptom resolution.

PSAP 2016 Book 2 • GI/Fluids and Nutrition 22 Selected Infections of the GI Tract and Liver

Burgos Chapter by JYT.indd 22 4/21/2016 3:04:18 PM 5. R.D.’s clinical examination and laboratory test data at Anoscopy is not available. Which one of the following is baseline and during his initial C. difficile episode are as best to recommend for this patient? follows: A. Ceftriaxone 250 mg intramuscularly one time plus azithromycin 1000 mg orally one time Laboratory At Baseline At First Episode B. Ceftriaxone 250 mg intramuscularly one time plus Hgb (g/dL) 11.3 11.2 doxycycline 100 mg orally twice daily for 7 days

SCr (mg/dL) 1.0 1.9 C. Cefixime 400 mg by mouth one time plus doxycycline 100 mg orally twice daily for 21 days 3 3 WBC (x 10 cells/mm ) 3 17.6 D. Ceftriaxone 250 mg intramuscularly one time plus BUN (mg/dL) 18 24 doxycycline 100 mg orally twice daily for 21 days

Blood pressure (mm Hg) 135/84 120/80 8. An 80-year-old man with hypertension and no known drug allergies presents to the clinic from home with right upper quadrant abdominal pain. He has not seen his phy- Which one of the following is the best categorization of sician in more than a year. Bile duct dilatation is evident R.D.’s initial C. difficile episode? on imaging. His temperature is 103.1°F (39.5°C), total bil- A. Mild irubin is 5.0 mg/dL, ALK is 1000 IU/L, and WBC is 15,000 B. Moderate cells/mm3. The patient is otherwise clinically stable, and C. Severe other laboratory values are normal. Acute cholangitis is D. Severe complicated diagnosed. Which one of the following is the best empiric 6. An HIV-negative man receives a diagnosis of acute proc- antibiotic to recommend for this patient? titis. He reports having sexual intercourse with a male A. Ampicillin/sulbactam partner 3 weeks ago. On the basis of the CDC 2015 STI B. Cefazolin plus metronidazole Treatment Guidelines, which one of the following is the C. Ceftriaxone best treatment and counseling point regarding how long D. Levofloxacin plus metronidazole the patient should abstain from sexual intercourse? 9. A patient with no significant medical history presents to A. Ceftriaxone 250 mg intramuscular plus azithromycin the ED from home with nausea, vomiting, and tenderness 1000 mg orally one time, abstain from intercourse over his gallbladder. His temperature is 104°F (40°C), until 7 days after the patient received the treatment. total bilirubin is 4.0 mg/dL, and WBC is 20 x 103 cells/ B. Ceftriaxone 250 mg intramuscular plus azithromycin mm3. Diagnostic imaging shows gallbladder thickening 1000 mg orally one time, abstain from intercourse and a gallstone obstructing the cystic duct. The patient’s until 7 days after both patient and partner have blood pressure is 60/40 mm Hg, and respiratory rate is 30 received treatment. breaths/minute; his mental status is altered. He is admit- C. Ceftriaxone 250 mg intramuscular one time plus ted to the ICU with a diagnosis of acute cholecystitis. The doxycycline 100 mg orally twice daily for 21 days, patient has no known drug allergies. Which one of the abstain from intercourse until the both the patient following is the best empiric antibiotic to recommend for and partner have completed the 21-day treatment this patient? regimen. A. Clindamycin plus moxifloxacin D. Ceftriaxone 250 mg intramuscular one time plus B. Levofloxacin plus metronidazole doxycycline 100 mg orally twice daily for 7 days, C. Linezolid plus piperacillin/tazobactam abstain from intercourse until the patient and D. Meropenem plus vancomycin his partner have completed the 7-day treatment regimen. 10. A 72-year-old woman with a history of diabetes has had intolerable pain from recurrent cholelithiasis. Elective 7. A 28-year-old man with HIV/AIDS and bipolar disorder is laparoscopic cholecystectomy is planned. She has no at a clinic for a scheduled follow-up. His laboratory val- known drug allergies. Which one of the following is best ues today are normal except the urine sample, which is to recommend for this patient regarding antibiotic pro- positive for Chlamydia. The patient reports having sexual phylaxis for surgery? activity with both men and women, and regularly is the receptive partner during unprotected anal intercourse. A. No antibiotic prophylaxis He reports increasing pain on defecation in recent weeks, B. A single dose of cefazolin within 60 minutes before which he attributes to rough sexual intercourse. Digi- surgery tal rectal examination reveals a palpable rectal fissure C. Cefazolin within 60 minutes before surgery and for or fistula at the 12 o’clock position with no discharge. 24 hours after surgery

PSAP 2016 Book 2 • GI/Fluids and Nutrition 23 Selected Infections of the GI Tract and Liver

Burgos Chapter by JYT.indd 23 4/21/2016 3:04:18 PM D. Cefazolin within 60 minutes before surgery and for of the following is best to recommend for prophylaxis for 48 hours after surgery this patient before ERCP? 11. A 22-year-old patient with no drug allergies or significant A. No antibiotic medical history presents with acute appendicitis and will B. Levofloxacin have an appendectomy. There is no evidence of perfora- C. Piperacillin/tazobactam tion of the appendix. A dose of antibiotic will be given for D. Vancomycin prophylaxis within 60 minutes of the incision. Which one 15. A hospital has an unexpected rise in the number of blood of the following intravenous antibiotics is best to recom- and bile infections caused by carbapenem-resistant mend for this patient? Enterobacteriaceae (CRE). An investigation reveals that A. Cefazolin each infected patient had recently undergone ERCP. The B. Ceftriaxone patients were treated for CRE infection with colistin, the C. Cefoxitin only antibiotic that was active. Which one of the follow- D. Levofloxacin ing is the best approach to stem the outbreak? 12. A retrospective study examined the incidence of C. A. Administer a prophylactic dose of colistin before difficile infection (CDI) after appendectomy for nonperfo- each ERCP procedure. rated appendicitis. The CDI occurred in 1.5% of patients B. Institute a program of gas sterilization of who received postoperative antibiotics and in none of duodenoscopes. the patients who did not receive postoperative antibiot- C. Disinfect contaminated duodenoscopes and verify ics. For CDI, which one of the following most accurately them to be free of pathogens. depicts the number needed to harm for administration of D. Replace duodenoscopes with instruments from a postoperative antibiotics in this study? new manufacturer. A. 15 16. A 23-year-old man (weight 60 kg) with no significant B. 33 medical history presents with fever, abdominal pain, and C. 67 marked hepatomegaly. Laboratory results include WBC D. 150 15 x 103 cells/mm3. Computed tomography reveals sev- 13. A patient underwent transarterial chemoembolization eral coalescing liver abscesses. Six months ago, the (TACE) for hepatocellular carcinoma 8 hours ago. He has patient spent 2 months in rural Vietnam as a teacher. no history of hepatobiliary procedures. He has abdom- Serologies are pending. Which one of the following is the inal pain, and his temperature is 100.8°F (38.2°C). The best empiric oral antibiotic therapy to recommend for patient otherwise feels well. His laboratory values are this patient? significant for a doubling of AST and ALT to 33 IU/L and A. Metronidazole 750 mg three times daily for 7 days 25 IU/L, respectively; an increase of total bilirubin from B. Metronidazole 750 mg three times daily for 7 days 0.9 mg/dL to 1.5 mg/dL; and an increase in WBC from 5 followed by paromomycin 500 mg three times daily x 103 cells/mm3 to 9 x 103 cells/mm3. Which one of the for 7 days following is the best next action to take for this patient? C. Paromomycin 500 mg three times daily for 7 days A. Conduct ultrasonography of the liver to look for D. Paromomycin 500 mg three times daily for 7 days abscess. followed by metronidazole 750 mg three times daily B. Monitor the patient for another day with supportive for 7 days care. 17. A 2-year-old boy and his mother (weight 70 kg) have both C. Initiate empiric antibiotics to treat a suspected received diagnoses of pinworm (Enterobius vermicularis). infection. Which one of the following is the best oral therapy to rec- D. Initiate the post-TACE antibiotic prophylaxis ommend for the mother? regimen. A. Albendazole 100 mg one time only 14. A 50-year-old man with hyperlipidemia and no known B. Mebendazole 400 mg daily for 2 days drug allergies is to undergo elective endoscopic ret- C. Praziquantel 1800 mg three times daily for 2 days rograde cholangiopancreatography (ERCP). He is D. Pyrantel pamoate 750 mg one time only asymptomatic, and his laboratory values are significant 18. A 30-year-old woman has arrived in the United States only for total bilirubin 4.0 mg/dL and ALK 400 IU/L. A as a refugee from Burma. She was pregnant at the time biliary stricture has been visualized by magnetic reso- of departure overseas, and treatment of parasites was nance cholangiopancreatography, and the endoscopist deferred. She lost the pregnancy in transit. Her phy- expects to achieve complete biliary drainage. Which one sician wants to use the CDC guideline for domestic

PSAP 2016 Book 2 • GI/Fluids and Nutrition 24 Selected Infections of the GI Tract and Liver

Burgos Chapter by JYT.indd 24 4/21/2016 3:04:18 PM management of arriving refugees to decide on parasite treatment. Which one of the following would be the best presumptive parasite treatment regimen for this patient? A. Albendazole plus ivermectin B. Albendazole plus ivermectin plus paromomycin C. Albendazole plus ivermectin plus paromomycin plus praziquantel D. Albendazole plus ivermectin plus praziquantel 19. A 52-year-old farmer came to the United States 6 years ago from Russia. He has echinococcosis secondary to Echinococcus multilocularis and has taken albendazole 400 mg twice daily for 1 month. Today, his laboratory results are WBC 2 x 103 cells/mm3, AST 60 IU/L, and ALT 90 IU/L. Albendazole sulfoxide concentration 4 hours after the morning dose is 2.2 micromoles/L. Which one of the following is best to recommend for this patient? A. Continue albendazole at the current dose. B. Decrease the albendazole dose. C. Discontinue albendazole today. D. Pause albendazole therapy for 2 weeks. 20. A man who emigrated 8 years ago from rural South Amer- ica to Florida presents with total bilirubin 8 mg/dL, ALK 340 IU/L, and intermittent abdominal pain. During ERCP, a worm identified as Fasciola hepatica is removed from a bile duct. The health care provider would also like to treat with a drug. Which one of the following is best to discuss with the provider regarding the preferred drug therapy? A. The drug concentration should be monitored. B. The drug must be taken on an empty stomach. C. The drug should be administered for 7 days. D. The drug should be requested from the CDC.

PSAP 2016 Book 2 • GI/Fluids and Nutrition 25 Selected Infections of the GI Tract and Liver

Burgos Chapter by JYT.indd 25 4/21/2016 3:04:18 PM