Infectious Disease Reports 2019; volume 11:8108

A case of of nosocomial infection, particularly in goodii infection related association with surgically implanted mate- Correspondence: Andrew Shelton, rials.1,2 However, only rarely have infec- Department of Internal Medicine, George to an indwelling catheter tions with M. goodii been associated with Washington University School of Medicine placed for the treatment CVC infections. We present a case of M. and Health Sciences, Ross Hall, 2300 Eye of chronic symptoms attributed goodii cultured from a CVC tip in the set- Street, NW, Washington, D.C. 20037, USA. ting of persistent M. goodii bacteremia and Tel.: +1.703-822-3047 - Fax: +1.828-649-3786. to Lyme disease E-mail: [email protected] pulmonary septic emboli following long- term exposure to broad-spectrum intra- Key words: Mycobacterium goodii, post Lyme Andrew Shelton,1 Luca Giurgea,2 venous antibiotics. This is only the second 3 4 disease syndrome, catheter-associated blood- Mahdi Moshgriz, Marc Siegel, reported CVC infection due to M. goodii, stream infection, nontuberculous mycobacte- 4 Hana Akselrod and the first case reported in a patient with ria. 1Department of Internal Medicine, extensive outpatient exposure to intra- venous broad-spectrum antibiotics. George Washington University School of Contributions: AS: conception and design of the work; acquisition, analysis, and interpreta- Medicine and Health Sciences, tion of data for the work; drafting and revision 2 Washington, DC; National Institute of of the work. LG, HA: design of the work; Allergy and Infectious Diseases, Case Report acquisition, analysis, and interpretation of data National Institutes of Health, Bethesda, for the work; drafting and revision of the MD; 3Department of Pathology, George A 32-year-old woman living in North work. MM, MS: design of the work; acquisi- Washington University Medical Center, Carolina but under the care of a local physi- tion, analysis, and interpretation of data for the cian in Washington DC for symptoms work; revision of the work. Washington, DC; 4Department of attributed to chronic Lyme disease present- Medicine, George Washington ed to George Washington University Conflict of interest: the authors declare no University Medical Faculty Associates, Hospital with fever, shortness of breath, and potential conflict of interest. Washington, DC, USA increasing confusion. Two years prior to the only current presentation, the patient had been Funding: this research was supported by the Intramural Research Program of the NIH, given a diagnosis of chronic Lyme disease NIAID. Abstract after she developed multiple symptoms including confusion, photophobia, arthral- Mycobacterium goodii has only rarely useReceived for publication: 13 March 2019. gia/myalgia, headaches, constipation, and been reported to cause invasive disease in Revision received: 25 July 2019. seizures. A computed axial tomography humans. Previously reported cases of M. Accepted for publication: 25 July 2019. (CT) scan of the chest at the time showed goodii infection have included prosthetic patchy infiltrates and she underwent a bron- This work is licensed under a Creative joint infections, pacemaker pocket infec- choscopy, which did not detect any abnor- Commons Attribution-NonCommercial 4.0 tions, and pneumonia. We present a case of mality including negative acid-fast bacilli International License (CC BY-NC 4.0). M. goodii bacteremia with concomitant pul- smear and culture. Subsequent imaging monary septic emboli that developed in a © showed resolution of those infiltrates. She Copyright: the Author(s), 2019 32-year-old woman with an indwelling cen- Licensee PAGEPress, Italy was treated with multiple oral regimens tral venous catheter (CVC). The CVC had Infectious Disease Reports 2019; 11:8108 including rifabutin, pyrimethamine, leucov- been placed one year previously for inter- doi:10.4081/idr.2019.8108 orin, metronidazole and ivermectin. One mittent treatment with intravenous, broad- year prior to her current presentation she spectrum antibiotics, administered by an had a subclavian CVC implanted for admin- outside physician for the treatment of symp- istration of intravenous antibiotics includ- revealed leukocytosis (white blood count toms attributed to chronic Lyme disease. ing meropenem, clindamycin, and tigecy- 11,370 cells/mL, 85% neutrophils). Despite our recommendations, the patient cline. Most recently, she had completed a Contrast CT chest showed bilaterally sym- declined follow-up in our Infectious three-week course of ciprofloxacin and metric opacification with bronchovascular Diseases clinic, opting to continueNon-commercial care meropenem every other day, ending several distribution and innumerable pulmonary under her chronic Lyme disease physician. weeks prior to her presentation. After devel- nodules (Figure 1). Multifocal pneumonia This case clearly demonstrates the potential opment of her current symptoms, she due to septic emboli was suspected, and for serious medical complications that can sought treatment in an emergency depart- vancomycin plus piperacillin-tazobactam arise from the inappropriate use of long- ment in North Carolina, where she was were started. A trans-thoracic echocardio- term intravenous antibiotics using a CVC to diagnosed with pneumonia and treated with gram (TTE) found no evidence of valvular treat non-specific symptoms attributed to azithromycin without improvement. She vegetations. No other foci of infection were Lyme disease and patients should be coun- then traveled to Washington, DC for evalu- apparent on physical examination. After 72 seled regarding these risks. ation by her local physician, and subse- hours anaerobic blood culture bottles quently presented to our institution. (BACTEC Plus Aerobic/F, Becton In the emergency department the patient Dickinson, Sparks, Maryland) revealed was noted to be febrile to 39.5°C, blood growth of beaded Gram-positive, acid-fast Introduction pressure 125/73 mmHg, heart rate 85 rods suggestive of mycobacterial species. Mycobacterium goodii is a rapidly beats/minute. Physical exam revealed After lengthy discussion with the growing non-tuberculous mycobacterium fatigued appearance with decreased breath patient and her family, the CVC was (rNTM) that was identified as a relative of sounds bilaterally, and a CVC with port removed. Culture of initial blood cultures in 1999. It is access in the left chest wall without evi- and the CVC tip revealed growth of M. becoming recognized as an emerging cause dence of infection. Laboratory studies goodii. The patient’s antibiotics were

[page 26] [Infectious Disease Reports 2019; 11:8108] Case Report empirically changed to azithromycin 500 mg intravenously daily, ciprofloxacin 400 mg intravenously every 12 hours, and meropenem 1 g intravenously every 8 hours. The patient clinically improved on this regimen. The patient returned to North Carolina before the identification and sensi- tivities of the mycobacterial species was available. Therefore, she was empirically switched to an oral regimen of trimetho- prim/sulfamethoxazole 800 mg/160 mg twice daily, azithromycin 250 mg once daily, and ciprofloxacin 500 mg twice daily for two-weeks from time of line removal. The patient was counseled extensively to avoid future placement of a CVC in the absence of a clear medical indication. Blood cultures drawn after CVC removal were negative at the time of her discharge but subsequent to discharge also grew M. good- ii. The patient cancelled her follow-up appointment in our Infectious Diseases clin- ic and she was lost to follow-up. The mycobacterial isolate was sent to Figure 1. Computed axial tomography of the chest performed with intravenous contrast Quest Diagnostics Labs (San Juan showing bilateral nodular opacifications in a bronchovascularonly distribution. Capistrano, California) for the beta subunit

Table 1. Cases of rapid-growing non-tuberculosis mycobacteria (rNTM) identifieduse in blood cultures at our institution, 2012-2018. Case Month/ Organism Central Line Culture Antibiotics Outcome Year line removed clearance 59-year-old man with ESRD 09/2018 M. chelonae CVC, tunneled Y Y ciprofloxacin and Infection resolved metronidazole for 7 days 32-year-old woman with 03/2018 M. goodii CVC, port Y N See text Declined follow-up “Chronic Lyme disease” 70-year-old man with 02/2018 M. mucogenicum PICC Y Y piperacillin/ Infection Parkinson’s Disease tazobactam for 2 weeks resolved 28-year-old man with 12/2017 M. mucogenicum No midline Y Y linezolid for 2 weeks Infection resolved Crohn’s disease 27-year-old woman with 10/2016 M. fortuitum CVC, tunneled Y Y ciprofloxacin and Infection resolved ESRD complex clarithromycin, followed by ciprofloxacin and linezolid Non-commercial for 3 months 70-year-old woman 08/2016 and M. fortuitum CVC, PICC Y Y* ciprofloxacin Cleared initially but with Crohn’s disease 04/2018 complex for 2 weeks recurred 1.5 years and recurrent urinary later with eventual tract infections clearance after second PICC line removal 31-year-old woman with 02/2016 M. mucogenicum CVC, port Y Y meropenem, Infection resolved renal transplant group unclear duration 43-year-old woman 12/2015 M. mucogenicum PICC Y Y cefepime for 6 weeks Infection resolved with native-valve group endocarditis 52-year-old man with HIV 09/2013 M. mucogenicum PICC Y Y piperacillin/ Infection resolved and recurrent urinary group tazobactam and tract infections daptomycin for 4 weeks 27-year-old woman with 11/2012 M. mucogenicum CVC, internal Y Y ciprofloxacin Infection resolved sickle cell anemia group jugular and linezolid for 2 weeks ESRD= end-stage renal disease, CVC = central venous catheter, PICC = peripherally inserted central catheter, Midline = peripherally inserted catheter, Y = blood cultures were drawn after line was removed and were immediately negative, N = blood cultures were not negative after line removal. *Two instances (see Outcome).

[Infectious Disease Reports 2019; 11:8108] [page 27] Case Report of RNA polymerase (rpoB) and 16S rDNA ative for M. tuberculosis complex, M. As illustrated, the identification and treat- sequencing which revealed the organism to avium complex, and M. kansasii. ment of rNTM organisms can pose particu- be genetically consistent with M. goodii Catheter-associated bloodstream infec- lar challenges including multi-drug resist- with an identity match of 99.86%. tions caused by rNTM are seen most fre- ance (especially in patients already exposed Sensitivity testing showed the organism to quently in patients with malignancies that to multiple antibiotics), reliance on special- be resistant to clarithromycin (MIC >16 require CVC for chemotherapy. These ty laboratory methods, and longer times to mcg/mL), intermediate to cefoxitin (MIC infections typically have greater than 90% definitive identification and sensitivity test- 32 mcg/mL), and susceptible to both clearance rate with catheter removal even in ing. Ultimately, there was a significant trust ciprofloxacin (MIC 1 mcg/mL) and the absence of antibiotic therapy.13,14 Unlike gap between the patient and our infectious trimethoprim/sulfamethoxazole (MIC the majority of cases of rNTM catheter- disease physicians, and the patient stated 0.5/9.5 mcg/mL). associated infections, our patient did not her intention to keep following with her clear her blood cultures immediately after “Lyme-literate” provider and was lost to catheter removal. This may have been due follow-up. to more persistent foci of infection from the Discussion septic emboli in her lungs, or possibly due rNTMs are hydrophobic, ubiquitous to an infected thrombus at the site of her organisms found in water and soil. They former long-term CVC. Upper-extremity Conclusions thrombosis has been described as a risk have been observed to form biofilms in Mycobacterial infections, including M. with the use of catheters similar to that used non-stagnant water piping, survive a variety goodii, should be considered as potential in our patient, with one study reporting 3 of environmental extremes (temperature, causes of CVC infections facilitating opti- times higher risk for such outcomes.15 pH, scarcity of nutrients), and are regarded mal diagnostic testing and use of appropri- While mycobacterial native valve endo- as resistant to disinfectants such as chlorine ate antibiotic regimens. Our patient’s CVC carditis is exceedingly rare,16 and a good- and phenol/glutaraldehyde based sub- and long-term use of antibiotics selected for 3 quality TTE was negative in our case, the stances. M. goodii has been associated with an unusual biofilm-producing pathogen: M. suspicion of secondary foci of infection soft tissue infection, osteomyelitis, bursitis, goodiionly. In contrast to published literature as warranted close follow-up in this patient, pneumonia, and achalasia- associated pul- well as to prior experience with rNTM 1,4,5 and possible extension of treatment dura- monary disease. Cases of M. goodii bloodstream infections at our institution, tion for longer than two weeks. infections have also been reported to com- blood cultures remained positive even after Unfortunately, the patient did not return for plicate a variety of surgical procedures and useCVC removal and initiation of appropriate 1,2 outpatient follow-up or additional imaging. devices, including; hardware, pacemaker antimicrobial therapy, suggesting the pres- 1,6 7 Macrolide resistance is a common con- devices, mitral valve annuloplasty, pros- ence of a persistent nidus of infection. The 8 9 cern when treating rNTM,17 and was docu- thetic heart valves, deep brain stimulators, patient was counseled on the need for close 10 mented in our isolate; the patient’s history intra-opthalmic devices, intra-abdominal outpatient follow-up with an infectious dis- 2 11 of receiving azithromycin monotherapy mesh, ventriculoperitoneal shunts, breast ease specialist and avoidance of future 12 4 prior to her presentation to our hospital may implants, and intravenous catheters. In long-term line placement without clear have contributed to this. The empiric multi- the majority of these cases involving pros- medical necessity. thetic material, clearance of the infection drug regimen that we started, including the was only achieved by removal of foreign intravenous ciprofloxacin and meropenem while she was an inpatient followed by oral material and administration of antibiotic References therapy. In only two cases was antibiotic ciprofloxacin, azithromycin, and sul- therapy alone successful despite retention famethoxazole/trimethoprim as an outpa- 1. Brown BA, Springer B, Steingrube VA, of hardware: one involving a deep brain tient, was supported by the susceptibility et al. Mycobacterium wolinskyi sp. nov. stimulator,11 and another a pacemaker pock- data and should have been adequate thera- and mycobacterium goodii sp. nov., two et infection.6 py. Due to persistent symptoms, patients new rapidly growing species related to A retrospective review of blood cultures with post-Lyme disease syndrome (PLDS) mycobacterium smegmatis and associ- positive for rNTM at our institution Non-commercialover the may seek alternative therapies that have ated with human wound infections: a last six years revealed ten episodes of limited supporting evidence and can be cooperative study from the International rNTM bacteremia in nine patients (in addi- associated with significant morbidity. Long- Working Group on mycobacterial tion to the case presented above) summa- term antibiotic therapy has not been shown . Int J Syst Bacteriol rized in Table 1. These included three cases to have any benefit for PLDS,18 but is a 1999;49:1493-511. of M. fortuitum complex, one case of M. clear risk factor for catheter infections and 2. Ferguson DD, Gershman K, Jensen B, cheloneae, and six cases of M. muco- selection of resistant organisms. The use of et al. Mycobacterium goodii infections genicum. In all cases, a CVC was implicat- antibiotics for the treatment of PLDS, espe- associated with surgical implants at col- ed, and subsequently removed. All cases cially when given intravenously, has been orado hospital. Emerg Infect Dis were treated antibiotics, although the regi- associated with increased hospitalization, 2004;10:1868-71. men and duration of treatment varied. With emergency department visits, and 3. De Groote MA, Huitt G. Infections due the exception of our case, clearance of the infection.19 To date, four cases of serious to rapidly growing mycobacteria. Clin bacteremia followed CVC removal. All of bloodstream infections associated with Infect Dis 2006;42:1756-63. the above isolates grew in standard catheters placed specifically for long-term 4. Wallace RJ Jr, Nash DR, Tsukamura M, BACTEC blood culture bottles, with subse- antibiotic treatment of symptoms attributed et al. Human disease due to mycobac- quent incubation on Löwenstein Jensen to Lyme disease have been reported, with terium smegmatis. J Infect Dis 20 media at 36°C with 5% CO2. All specimens one case resulting in death. Our patient 1988;158:52-9. were sent to Quest Diagnostics for identifi- represents the first case of PLDS treatment 5. Martínez-González D, Franco J, cation after in-house DNA probes were neg- complicated by a mycobacterial infection. Navarro-Ortega D, et al. Achalasia and

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