OCTOBER 2017 DRUG ANTIBIOTICS

URINARY TRACT INFECTIONS IN ADULTS

This optimal usage guide is mainly intended for primary care health professionnals. It is provided for information purposes only and should not replace the clinician’s judgement. The recommendations were developed using a systematic approach and are supported by the scientific literature and the knowledge and experience of Quebec clinicians and experts. They do not apply to pregnant women or to severe urinary tract infections requiring parenteral therapy. For more details, go to inesss.qc.ca.

GENERAL CONSIDERATIONS TERMINOLOGY

Uncomplicated urinary Acute, sporadic or recurrent urinary tract infection (cystitis or pyelonephritis) in a URINARY TRACT INFECTIONS IN ADULTS tract infection healthy woman, regardless of her age.

Any other urinary tract infection, particularly in a pregnant woman, a man, any Complicated or at risk of individual with an anatomical or functional abnormality of the urinary system, a becoming complicated urinary catheter, a previous urologic manipulation or uncontrolled diabetes, or any immunosuppressed individual.

A urinary tract infection that occurs more than 2 times every 6 months or more than 3 times a year. Most cases are a reinfection, i.e., another infection of the Recurrent urinary tract urinary system. It may also be a persistent infection due to bacterial resistance, infection inadequate treatment or an anatomical or functional abnormality of the urinary system, which recurs usually very quickly, i.e., within 2 to 4 weeks maximum after initial treatment.

Asymptomatic bacteriuria Presence of bacteria in the urine with no symptoms or clinical signs.

PATHOGENS

Common Rare (may require further investigation)

Examples : • Escherichia coli • Enterobacter spp. • Klebsiella pneumoniae • Proteus mirabilis • Staphylococcus saprophyticus • Pseudomonas aeruginosa • Enterococcus

• Staphylococcus aureus Stay up to date at inesss.qc.ca URINARY TRACT Stay up to date at inesss.qc.ca INFECTIONS IN ADULTS 1. Women diagnosis to pointing Signs another and symptoms Pyelonephritis Cystitis Signs and symptoms All patients All Men Women Men „ „ „ „ DIAGNOSIS URINE ANALYSIS ANDCULTURE DIFFERENTIAL DIAGNOSIS abnormal urineanalysisandculture results). Elderly patient SYMPTOMATOLOGY • Nausea, vomiting Nausea, • Chills • Fever • urinating when pain and sensation • Burning frequency Urinary • • Dysuria „ „ „ „ Urine culture Urine dipstick  which may point to anotherdiagnosis. Diagnosis isbasedonthecombination ofsymptoms andclinicalsigns andontheabsence ofclinicalmanifestations, Cystitis isnotassociated withaltered vitalsigns orelevated temperature. • • • • • • • • • • • • infection, except cases(e.g., incertain urosepsis). To beavoided tract catheter with nosymptoms inpatients orclinicalsigns withanindwelling ofurinary urinary Recommended inthefollowing cases one month). incasesofuncomplicatedOptional ordocumented recurrent cystitis (except cystitis ifarecurrence occurred within esteraseAbsence and/ornitrites ofleukocyte inasymptomatic patient Presence esterase, symptoms ofleukocyte nitrites anddenovo urinary Simple, andreliable low-cost -  -  -  Recent to symptoms. trip anarea at for risk multidrug-resistant andurinary bacteria Combination ofsymptoms andclinicalsigns butnegative analysis. urine persisting symptoms orfailedantibiotic treatment. Uncomplicated acute pyelonephritis (APN), complicated infection, tract orat ofbecoming risk complicated urinary : Atypical andnon-specificsymptomatology: Atypical (e.g., confusion, incontinence). Consider adifferential symptoms appearorpersist(with infection diagnosis tract except ifspecificurinary 1 : recommended for any type of suspected urinary tract infection. tract : recommended for urinary any ofsuspected type intra-abdominal infections (e.g., appendicitis, diverticulitis). (e.g., appendicitis, infections intra-abdominal infections transmitted Sexually Prostatitis, epididymo-orchitis. Prostatitis, ovarian cyst). ruptured pregnancy, disease, ectopic inflammatory (e.g., pelvic pathologies gynecological infections, Vaginal pelvic or examination. testicular or Pain by prostatic elicited symptoms. Vaginal itching, pregnancy discharge, vulvar : • Cystitis present) (often symptoms •  •  pain • Suprapubic • Hematuria urinary tract infections. tract urinary If isolated, cloudyorfoul-smelling urineshouldbeconsidered carefully asitisnotspecific to (Murphy’s sign) punch Costovertebral angle tenderness urine foul-smelling or Cloudy , urinary calculus with or without urosepsis, other other urosepsis, without or with calculus , urinary : goodpositive predictive value (≈ 90 %). : goodnegative predictive value (≈ 90 %). !

TREATMENT PRINCIPLES

„„Asymptomatic bacteriuria should not be treated, except before urology interventions. „„When selecting a medication, local antibiotic resistance should be taken into account. It should never exceed 20 % (except if there is no alternative treatment).

Data on Escherichia coli resistance to certain antibiotics in Québec1

Fosfomycin Trimethoprim- Antibiotics Nitrofurantoin Ciprofloxacin tromethamine sulfamethoxazole

Resistance Less than 5 % 5–10 % 10–15 % 15–20 %

1. Regional variations exist.

URINARY TRACT INFECTIONS IN ADULTS „„Fluoroquinolones should not be prescribed to treat uncomplicated cystitis (except if there is no alternative treatment). „„Recent use of antibiotics, a trip to an area at high risk for antibiotic resistance (e.g., Middle East, Far East, Indian sub-continent, Sub-Saharan Africa) and a recent hospital stay increase the risk of bacterial resistance. „„ In case of failed hygienic and dietary measures (e.g., sufficient hydration, personal hygiene, postcoital voiding) and after urinary system exploration (identification of anatomical or functional abnormalities), recurrent uncomplicated cystitis may be treated with the following :

••Postcoital antibiotic prophylaxis for 6 months Follow-up is recommended after 6 months to reassess ••Self-start antibiotic therapy (if signs or symptoms are treatment relevance for recurrent uncomplicated cystitis detected by the patient) and check what changes the patient has made, if any ••Continuous antibiotic prophylaxis for 3 to 6 months (e.g., contraceptive method, sexual activity).

„„Current knowledge does not support, as non-antibiotic prophylaxis for urinary tract infections, the use of cranberries or intravaginal probiotics, for which efficacy data is contradictory; using oral estrogen, whose efficacy has not been proven; or vaginal estrogen, as there is no statistically significant data on their use in menopausal women. Stay up to date at inesss.qc.ca URINARY TRACT Stay up to date at inesss.qc.ca INFECTIONS IN ADULTS 7. 6. 5. 4. 3. 2. 1. N/A : Amoxicillin-clavulanate Fluoroquinolones are presented basedoncost (lowest to highest). The 7:1formulation (875/125mg)POBIDofamoxicillin-clavulanate ispreferred dueto itshigherdigestive tolerance. Although cefuroxime andcefprozil are indicated for thetreatment ofuncomplicated there thisuse. cystitis, islimited evidence supporting are presentedBeta-lactams order inalphabetical ofgenericname. Fosfomycin, andfluoroquinolones are beta-lactams usuallynot recommended asantibiotic prophylaxis options. Cystitis isconsidered recurrent whenthere are more than2episodesover 6months ormore antibiotic therapy than3ayear; issimilarto self-start first-linetreatment. Antibiotics are presented basedon ANTIBIOTIC TREATMENT Not applicable; macrocrystals only macrocrystals Fluoroquinolones sulfamethoxazole Nitrofurantoin, Nitrofurantoin, Ciprofloxacin XL Ciprofloxacin Beta-lactams Nitrofurantoin Nitrofurantoin Trimethoprim- tromethamine monohydrate/ macrocrystals Trimethoprim Ciprofloxacin Levofloxacin Levofloxacin Antibiotics Fosfomycin Fosfomycin Antibiotics Norfloxacin Cephalexin Cefadroxil Cefixime DS : ALTERNATIVE TREATMENT IN CASE OF CONTRAINDICATION TO ALL FIRST-LINE ANTIBIOTICS TO FIRST-LINE ALL CONTRAINDICATION OF ALTERNATIVE CASE IN TREATMENT Double strength. Double 1 4,5 7 Escherichia coli ANTIBIOTIC TREATMENTANTIBIOTIC UNCOMPLICATED OF CYSTITIS resistance (leastto most) andcost (lowest to highest). 875/125 BID PO mg 160/800 BID PO mg (medication allergy, intolerance, resistance or interaction) or resistance intolerance, allergy, (medication FIRST-LINE 500 mg PO QID QID PO mg 500 500 mg PO BID PO mg 500 400 mg PO DIE PO mg 400 100 BID PO mg 100 BID PO mg (if all first-line antibiotics fail or have adverse effects) adverse haveor fail antibiotics first-line all (if 50 QID PO mg (1 DS tablet) Dosage 3 gPO 400 mg PO BID PO mg 400 250 BID PO mg 500 mg PO DIE PO mg 500 250 mg PO DIE 250 DIE PO mg Dosage SECOND-LINE 6 In a single dose asingle In

Duration 3 days 3 days 7 days 7 days 5 days continuous (3 6months) to continuous within 2 hours if postcoital postcoital if 2hours within Postcoital (6 or months) Postcoital RECURRENT CYSTITIS RECURRENT antibiotic prophylaxis antibiotic within 2 hours of sexual sexual of 2hours within within 2 hours of sexual sexual of 2hours within or DIE or 3 times/week 3times/week or DIE or or DIE if continuous intercourse or DIE intercourse DIE or 80/400 PO mg 50-100 PO mg if continuous if continuous 100 PO mg intercourse Duration 3 days N/A N/A

: : : 2,3 URINARY TRACT Stay up to date at inesss.qc.ca INFECTIONS IN ADULTS APN : 5. 4. 3. 2. 1. „ „ „ Amoxicillin-clavulanate The 7:1formulation (875/125mg)POBIDofamoxicillin-clavulanate ispreferred dueto itshigherdigestive tolerance. Although cefuroxime isindicated infections, there for thisuse. thetreatment tract islimited evidence supporting ofurinary are presentedBeta-lactams order inalphabetical ofgenericname. Fluoroquinolones are presented basedoncost (lowest to highest). For thetreatment ofuncomplicated, complicated orat riskofbecoming complicated APN. FOLLOW-UP Acute pyelonephritis; Fluoroquinolones „ „ „ sulfamethoxazole sulfamethoxazole first-line investigations (ultrasound, computed system).tomography oftheurinary colony,bacteria whichincreases thenumberofrecurring infections. These conditions with canbedetected anatomicalSome conditions (e.g., lithiasis, significant mayresidual urine) contribute to maintaining apersistent caseofrecurrenceIn ortreatment failure, before culture aurine shouldbeperformed anewtreatment isprescribed. Patient follow-up mainly inthefollowing situations isperformed Ciprofloxacin XL Ciprofloxacin Beta-lactams Trimethoprim- • • • • Ciprofloxacin Levofloxacin • • • • Antibiotics Cephalexin After antibiotic prophylaxis isinitiated, to assessitsrelevance anddetermine ifitshouldbecontinued (within2to symptoms 4weeks) reappearIf quickly symptoms persistdespiteIf treatment cultureAfter urine Cefadroxil Cefixime XL : ANTIBIOTIC TREATMENT FOLLOWING ANTIBIOTIC SENSITIVITY TESTING ONLY TESTING SENSITIVITY ANTIBIOTIC FOLLOWING TREATMENT ANTIBIOTIC Extended release. Extended 3,4 ANTIBIOTIC TREATMENT OF UNCOMPLICATED APN AND COMPLICATED APN AND UNCOMPLICATED OF TREATMENT ANTIBIOTIC OR AT RISK OF BECOMING COMPLICATED URINARY TRACT INFECTIONS TRACT COMPLICATED URINARY ATOR BECOMING OF RISK 2 875/125 BID PO mg 160/800mg BID PO 1 000 mg PO DIE PO mg 1 000 500 mg PO QID PO mg 500 500 mg PO BID PO mg 500 500 mg PO BID PO mg 500 400 mg PO DIE PO mg 400 500 mg PO DIE PO mg 500 Dosage FIRST-LINE 5 : 7 to 10 days Cystitis : Men Women 10 Duration to 14 days 10 to 14 days : 7days 10 to 14 days APN 1 URINARY TRACT Stay up to date at inesss.qc.ca INFECTIONS IN ADULTS the source ismentioned. for non-commercial useispermitted on condition that Any reproduction ofthisdocument inwholeorpart „ MAIN REFERENCES CRITERIA FORSPECIALISTREFERRAL „ pyelo¬nephritis inwomen: andtheEuropean ofAmerica for Diseases. A2010update andInfectious ClinicalInfec Microbiology DiseasesSociety Society by theInfectious Please note that otherreferences have beenconsulted. Société dePathologie deLangueFrançaise Infectieuse (SPILF).Diagnostic etantibiothérapie communautaires desinfectionsurinaires bactériennes del'adulte. 2015. http://www.sign.ac.uk/sign-88-management-of-suspected-bacterial-urinary-tract-infection-in-adults.html. infectioninadults(SIGN88).Edinburgh: tract SIGN;2012.Accessible Scottish Intercollegiate at: urinary bacterial ofsuspected (SIGN).Management GuidelinesNetwork practiceguides/uti/uti.pdf. Urinary Medicine, University ofMichigan. TractMichigan –Guidelinesfor Infection ClinicalCare Ambulatory. 2016.Accessible at: https://www.med.umich.edu/1info/FHP/ tious Diseases2011;52(5):e103-e20. Hooton Gupta K, TM, Naber KG, Wullt B, Colgan LG, R, Miller Dason S,JT, A.Guidelinesfor infection inwomen. thediagnosis tract Kapoor 2011. andmanagement ofrecurrent urinary https://uroweb.org/guideline/urological-infections/#5. R,Bruyère G,Pickard R,Bartoletti F,Bonkat SE, Geerlings Wagenlehner F, Wullt B, etal.Urological Infections. European 2016.Accessible Association ofUrology; at: analysis ofrandomized controlled trials. The ofUrology Journal 2013;190(6):1981-9. Beerepoot MA, SE, van HaarstEP, Geerlings van Charante G.Nonantibiotic NM,terprophylaxis Riet infections:Asystematic for tract review recurrent andmeta- urinary Referral to aspecialistisindicated inthefollowing cases • • • • • • • • Anatomical or functional abnormality of the urinary system oftheurinary Anatomical abnormality orfunctional Recurrent uncomplicated APNorany recurrent complicated infection tract oratofbecoming risk complicated urinary Hydronephrosis orpersistent post-void residual system ofmore urine than150mlinthelower urinary Recurrence causedby anunusualpathogen (e.g., Pseudomonas aeruginosa, Proteus mirabilis ) . International clinical practice guidelinesforet al.Internationalclinicalpractice thetreatment ofacute uncomplicated and cystitis : -