In-hospital management of urinary tract infections

Actualités néphrologiques Jean Hamburger Necker

Mai 2019

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In-hospital management of urinary tract infections :

difficult situations

In-hospital management of urinary tract infections : difficult situations

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• Infection is severe > ex. severe urinary tract infections

• Background is tricky > ex. urinary tract infections in pregnancy

• Bug is resistant > ex. new betalactams

• Localization is tricky > ex. infection of kidney cysts

Severe pyelonephritis Sepsis : qSOFA ≥ 2

Septic shock

Surgery requirement

To be distinguished from UTI at risk of complicationAny urinary tract anatomical / functional disorder

Pregnancy

Frail elderly patient

Creatinine clearance < 30 ml/min

Severe immunodeficiency

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Q SOFARR ≥ 22/minSBP < 100mmHgAltered consciousness

Conférence de consensus SPILF 2014- 2017

Severe pyelonephritis

• Work-up within 24 hoursUrine culture, creatinin, blood culture, urinary tract CT scan

• Antibiotics: betalactam + amikacin

• How to select the appropriate betalactam: 2-3 questions > 3G-cephalosporin allergy ?

> Has ESBL-E carriage/infection been documented in the past 6 months ?

> In case of septic shock : is there a risk for ESBL-E carriage?

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No septic shock

Parenteral 3G-C + amikacin

Severe allergy to penicillinsor allergy to 3G-C > aztreonam + amikacin

Aztreonam CI in case of delayed hypersensitivity- DRESS syndrome- Lyell, Stevens-Johnson

ESBL-E carriage /infection < 6 months> Choice based on prior identification


CefotaximeCeftriaxone


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ESBL-E carriage /infection < 6 months

Risk of ESBL-E infection

Septic shock



Pas de choc septique

C3G parentérale + amikacine

Allergie grave pénicillines ou allergie C3G> aztréonam + amikacine

Colonisation /infection E-BLSE < 6 mois> Prendre en compte, selon antibiogramme

No septic shock



ESBL-E carriage /infection < 6 months> Choice based on prior identification


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Risk factors for ESBL-E infection :- colonization /infection < 6 months- amox-clav/2-3G-C /FQ < 6 months- travel to an ESBL-E endemic area- hospitalization < 3 months- living in a long-term care facility

> Carbapenem + amikacin


Risk of ESBL infection

Septic shock




Drainage of any obstruction

Clinical monitoring

Oral switch at 48 hrs > adapted to identification,

Treatment duration : 10 days (longer in abscesses)

Concomitant bacteremia does not require longer treatment duration

Initial severity does not require longer treatment duration

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Pyelonephritis in pregnancy• Incidence 0.5%-1% of pregnancies

• Mechanical and hormonal risk factors

• Mostly T2/T3 : 80-90%

• Ecology is similar to non pregnant patients

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Wing AJOG 2014

Duff Clin Obstet Gynecol 1984

Pathogen Frequency

E. coli 82%

Streptococcus B 21%

K. pneumoniae 7%

Proteus sp. 5%

Enterococcus sp. 5%

Wing AJOG 2014Hill Obstet Gynecol 2005

Pyelonephritis in pregnancy

• Bacteremia : 2-20% cas

• Pyelonephritis infections account for 55%

of E. coli bacteremia during pregnancy

• May lead to sepsis /septic shock 0.5- 2%

• May lead to premature delivery 10%

• May lead to recurrences up to 23%

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Wing AJOG 2014Martin AJOG 2006

Surgers CMI 2014

Wing AJOG 2014

Archabald AJOG 2009

Gilstrap Obstet Gynecol 1981

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Pas de choc septique

CiprofloxacinMay be considered during pregnancy

AztreonamAllowed during pregnancy

Amikacin / GentamicinAllowed during pregnancy

No septic shock

Parenteral 3G-C +/- amikacin

Severe allergy to penicillins /allergy to 3G-C > aztreonam + amikacin> ciprofloxacin if no exposure < 6 months


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Colonisation /infection E-BLSE < 6 mois

Risque d’infection à E-BLSE

Choc septique

C3G parentérale + amikacine

Allergie grave pénicillines ou allergie C3G> aztréonam+ amikacine

Allergie grave pénicillines ou allergie C3G> aztréonam +/- amikacine< 6 mois

No septic shock

Parenteral 3G-C +/- amikacin

Severe allergy to penicillins /allergy to 3G-C > aztreonam + amikacin> ciprofloxacin if no exposure < 6 months


Risk of ESBL-E infection

Septic shock




• Work-up

Urine culture, creatinin, blood culture if severe/ dg uncertainties

Echography if hyperalgic /sepsis

Obstetrical evaluation

• Oral switch with compatible antibiotics

• Treatment duration 10-14days

• Urine culture 10d after antibiotic completion then /month until delivery

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Antibiotics and pregnancy

Yes Yes if… No

Betalactams ClavulanateAvoid at term

Cyclins

Macrolides Synergistins

CotrimoxazoleTeratogenic < 10SAAvoid at term

Kanamycin, Streptomycin

Furane Fosfomycin

CiprofloxacinIf no alternative

Other quinolon

INH, RMPPZA, ETB

AmikacinGentamicinX1/d , > 3 days

Colimycin

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Czeizel Reprod Toxicol 2001Hernandez-Diaz NEJM 2000

Briggs 9th Ed. 2012

New betalactamsfor resistant enterobacteria

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FQ/amin/3G-R E. coli

FQ-R E. coli 3G-R E. coli

Carbapenem-R K. Pn

ECDC2017

Aztreonam if no add. resistance

CarbapenemPeni+ inhib +/-TemocillinCefoxitin

Ruppé Ann Intensive Care 2015

C4GCarbapénèmes

CAZAZMCEPC3GMight work if no add. resistance

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•Ceftolozane- Tazobactam> Zerbaxa

Caftazidime – Avibactam> Zavicefta

Inhibitor Is a betalactaminTargets class A enzymes

Is not a betalactaminTargets class A, C, D enzymes

Betalactam Cephalosporin derived from ceftazidime X 2 affinity for PBP Increased resistance to AmpC Much less AmpC induction

Cephalosporin

Streptococci (not Enterococcus sp.)Aerobic Gram negative bacteriaPseudomonas aeruginosaNo : Staphylococci, Stenotrophomonas sp., Acinetobacter sp. Limited anti anaerobic effect

New betalactamsfor MDR- enterobacteria

COMAI APHP 2018Van Duyn , Bonomo CID 2016

20% E. coli BLSE are resistant Farrell AAC 201350% KP BLSE are resistant Sader JAC 2014

CFT/TAZ

CAZ/AVI

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•

Ceftolozane- Tazobactam> Zerbaxa

Caftazidime- Avibactam> Zavicefta

PK/PD IV only, 1g/500mg x 3/dKidney elimination , dialysedDouble dose in VAPAdapt if Cl < 50 ml/min

IV only, 2g/0,5g x 3/dKidney elimination , dialysed

Adapt if Cl < 50 ml/min

Indic. Complicated intra-abdominal infectionsComplicated UTI

Complicated intraabdominal infectionsComplicated UTINosocomial Pneumonias/VAP ++

In documented infections only Zerbaxa ++ Pseudomonas aeruginosa cefta-R Zavicefta ++ in some ESBL-E and OXA-48 documented infections Impact on the gut flora : no comparative study Cost ++

New betalactams for MDR- enterobacteria

COMAI APHP 2018Van Duyn , Bonomo CID 2016

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COMAI APHP

Cyst infections in polycystic kidney disease• Cyst infections requiring hospitalization reported in 9% ADPKD

• Cyst infections are associated with morbi-moratlity• Up to 7% mortality

• Enhanced renal impairment

• Sources of infection• Ascendant/hematogenous/nosocomial

• A diagnostic and therapeutic challenge

• Few available data

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Sallée Clin J Am Soc Nephrol 2009

Fick Clin J Am Soc Nephrol 1995Cornec-Le Gall J Am Soc Nephrol 2016


Sallée Clin J Am Soc Nephrol 2009Suwabe EJCMID 2015

Lantinga NDT 2015Sklar AJKD 1985

ADPKD, KDIGO Guidelines, Kidney Int 2015

• Clinical presentation is not specific

> 2 main differential diagnoses = pyelonephritis, cyst hemorrhage

> Pyelonephritis and cyst infection may coexist in the same ADPKD patient

> Hemorrhages may superinfect

> Kidney transplanted ADPKD : higher risk of native kidney infections

Non-functional end-stage polycystic kidneys may also be infected

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Cyst infection in ADPKDA diagnosis challenge

Ziebell Clin Nephrol 2002

•Microbiological presentation

> Same ecology as other UTI

> Both urine and blood cultures may be negative in 25%

> Gold standard : cyst punction

• Diagnosis criteria

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Oh Plos ONE 2018Sallée Clin J Am Soc Nephrol 2009

Suwabe EJCMID 2015

Fever > 38°5C > 3 daysAbdominal PainCRP > 50 mg/LNo recent bleeding on CT scanNo alternate cause of fever

Lantinga NDT 2015

• Radiological presentation non specific and not sensitive

• Echography• Hyperechoic

• Heterogeneous

• Internal septation

• CT scan• Irregular

• High attenuation

• Peripherical C+ enhancement

• Pericystic infiltration

•MR imaging > similar

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Oh PLOSONE 2018

• Sensibility is poor

CT and MRI show contributive images in 18 and 40% of cyst infection cases

CT and MRI yield negative results in >50% cases confimed by cyst punction

• Specificity is low

Intraluminal heterogeneity may be seen in uninfected cysts (cellular debris)

Contrast enhancement lining cyst walls can be caused by inflammation

• Administration of contrast agents may be contra-indicated

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Jouret NDT 2012


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• Pet 18FDG

18FDG not nephrotoxic

Localization

Follow-up : negativation within 9 weeks

False negative results described

Timing?

Specificity ? > Hemorrhages/pericystic pyelonephritis/tumoral lesion

Cost and availability?

Jouret Clin J Am Soc Nephrol 2011Neuville PLoSONE 2016

Bobot CMI 2016

ADPKD, KDIGO Guidelines, Kidney Int 2015

Cyst infections in ADPKDA therapeutic challenge

No therapeutic trial

Intracyst diffusion of antibiotics• Glomerular filtration

• Transepithelial diffusion

• Proximal vs distal cyst

• Lipophilic/phobic

Quinolons

Cotrimoxazole

Clindamycin

Metronidazole

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Moleculs Cyst/plasma ratio Reference

Ciprofloxacin 2-4.4 Elzinga AAC 1987; Telenti Mayo Clin Proc 1990

Levofloxacin 0.96 Hiyama AJKD 2006

Trimethoprim 3.9-8/ 1-23 Elzinga kidn Int 1987; Schwab AJKD 1986

Sulfamethox. 0.43 Elzinga kidn Int 1987

Gentamicin 0.18-0.34 Muther Kidney Int 1981; Schwab AJKD1083

Amikacine 0 Bennett AJKD 1985

Ticarcilline 0.12 Muther Kidney Int 1981

Meropenem 0.04-0.13 Hamanoue BMCN 2018

Cefotaxime 0 after 1 dose Bennett AJKD 1985

Amoxicillin 0-4.6 after 1-8 d Bennett AJKD 1985

Metronidazole 0.8-1 Bennett AJKD 1985

Vancomycin 0.06-0.61 Bennett AJKD 1985

Clindamycin 0.52-069/2.4-8.7 Bennett AJKD 1985; Schwab 1983

ADPKD, KDIGO Guidelines, Kidney Int 2015Adapted from Sallée CJASN 2009


Diffusion, although low, might be above the MIC

Diffusion might be enhanced in infected cysts

> amikacin cyst/plasma ratio 0 in uninfected cyst 0.5 in infected cyst

Slow delayed diffusion > prefer longer treatments

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Ohkawa Nephron 1991

Bennett AJKD 1985


Treatment failure requiring drainage reported in up to 30% of cases

Parameters associated with failure • Cyst size > 5cm

• Non E. coli bacteria

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Julien DANGOngoing study

Retrospective monocentric cohort140 episodes : 91 patients 56 episodes in Tx patients 2000-2018Confirmed : by punctionProbable : clin + RxPossible : clin

Survival without recurrentUTI

0 100 300 400

0

50

100Cotrimoxazole (n=6)

Fluoroquinolone (n=32)

Beta-Lactam (n=24)

log-rank p=0.052

200

Days

Julien DANG Thèse de Médecine en cours


Treatment failure requiring drainage reported in up to 30% of cases

Parameters associated with failure • Cyst size > 5cm

• Non E. coli bacteria

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Julien DANGOngoing study

Retrospective monocentric cohort140 episodes : 91 patients 56 episodes in Tx patients 2000-2018Confirmed : by punctionProbable : clin + RxPossible : clin

Survival without recurrentUTI

0 100 300 400

0

50

100ATB > 28 days (n=47)

ATB 22-28 days (n=28)

ATB 15-21 days (n=48)

ATB < 15 days (n=12)

log-rank p<0.001

200

Days



• Prefer antibiotics with good cyst diffusion

• Prefer long treatment duration > 21 days

• Timing of cyst punction ?

• Use of Pet 18FDG to monitor treatment ?

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Thank you for your attention

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Documents

In-hospital management of urinary tract infections