Breaking Antimicrobial Resistance: High-Dose Amoxicillin with Clavulanic Acid for Urinary Tract Infections Due to Extended-Spectrum Beta-Lactamase (ESBL)-Producing Klebsiella pneumoniae

Background Carbapenems are the primary treatment for urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae. However, the recurrence rate is high, and patients often require rehospitalization. We present the results of an observational study on patients with recurrent UTIs who were treated in an outpatient setting with maximal therapeutic oral doses of amoxicillin with clavulanic acid. Material/Methods All patients had pyuria and ESBL-producing K. pneumoniae in urine culture. The starting dosage was 2875 g of amoxicillin twice daily and 125 mg of clavulanic acid twice daily. We down-titrated the doses every 7–14 days and continued prophylactic therapy with amoxicillin/clavulanic acid at 250/125 mg for up to 3 months. We defined therapeutic failure as ESBL-positive K. pneumoniae in urine culture during therapy and recurrence as positive urine culture with the same strain within 1 month after the end of treatment. Results We included 9 patients: 7 kidney graft recipients, 1 liver graft recipient, and 1 patient with chronic kidney disease. We observed no therapeutic failures and no recurrences in the study group during the study period. In 1 case, the patient experienced a subsequent UTI caused by ESBL-producing K. pneumoniae 4 months after completing the therapy. Conclusions In conclusion, it is possible to break the resistance of ESBL-producing K. pneumoniae strains with high doses of oral amoxicillin with clavulanic acid. Such treatment could be an alternative to carbapenems in select cases.

[1]  Bhavesh Kotak,et al.  High-Dose amoxicillin supported with clavulanic acid as empirical therapy in acute otitis media , 2021 .

[2]  Huijuan Wang,et al.  Resistance Trends of Klebsiella pneumoniae Causing Urinary Tract Infections in Chongqing, 2011–2019 , 2021, Infection and drug resistance.

[3]  E. Pérez-Nadales,et al.  Efficacy of β‐lactam/β‐lactamase inhibitors to treat extended‐spectrum beta‐lactamase‐producing Enterobacterales bacteremia secondary to urinary tract infection in kidney transplant recipients (INCREMENT‐SOT Project) , 2020, Transplant infectious disease : an official journal of the Transplantation Society.

[4]  J. Pascual,et al.  Oral fosfomycin for the treatment of lower urinary tract infections among kidney transplant recipients—Results of a Spanish multicenter cohort , 2020, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[5]  Pia Abel zur Wiesch,et al.  Identifying the drivers of multidrug-resistant Klebsiella pneumoniae at a European level , 2019, PLoS Comput. Biol..

[6]  J. Rodríguez-Baño,et al.  Current options for the treatment of infections due to extended-spectrum beta-lactamase-producing Enterobacteriaceae in different groups of patients. , 2019, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[7]  L. Gesualdo,et al.  Updates on urinary tract infections in kidney transplantation , 2019, Journal of Nephrology.

[8]  Y. Chong,et al.  Current epidemiology, genetic evolution and clinical impact of extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae. , 2018, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases.

[9]  M. Ouellette,et al.  Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. , 2017, The Lancet. Infectious diseases.

[10]  E. Mylonakis,et al.  Urinary tract infections caused by ESBL‐producing Enterobacteriaceae in renal transplant recipients: A systematic review and meta‐analysis , 2017, Transplant infectious disease : an official journal of the Transplantation Society.

[11]  Young Bae Kim,et al.  Antimicrobial Resistance of Hypervirulent Klebsiella pneumoniae: Epidemiology, Hypervirulence-Associated Determinants, and Resistance Mechanisms , 2017, Front. Cell. Infect. Microbiol..

[12]  M. Betjes,et al.  Urinary Tract Infections After Kidney Transplantation: A Risk Factor Analysis of 417 Patients. , 2017, Annals of transplantation.

[13]  N. Sivakumar,et al.  Extended spectrum β‐lactamase producing Escherichia coli and Klebsiella pneumoniae: critical tools for antibiotic resistance pattern , 2017, Journal of basic microbiology.

[14]  David J. Edwards,et al.  Gastrointestinal Carriage Is a Major Reservoir of Klebsiella pneumoniae Infection in Intensive Care Patients , 2017, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[15]  D. Greenberg,et al.  Primary osteomyelitis caused by hypervirulent Klebsiella pneumoniae. , 2016, The Lancet. Infectious diseases.

[16]  J. Mecsas,et al.  Klebsiella pneumoniae: Going on the Offense with a Strong Defense , 2016, Microbiology and Molecular Reviews.

[17]  O. Vanderkooi,et al.  Time to reconsider routine high-dose amoxicillin for community-acquired pneumonia in all Canadian children. , 2016, Paediatrics & child health.

[18]  G. Dube,et al.  Epidemiology and outcomes of carbapenem‐resistant Klebsiella pneumoniae bacteriuria in kidney transplant recipients , 2015, Transplant infectious disease : an official journal of the Transplantation Society.

[19]  M. Mamzer,et al.  ESBL-producing enterobacteriaceae-related urinary tract infections in kidney transplant recipients: incidence and risk factors for recurrence , 2015, Infectious diseases.

[20]  D. Paterson,et al.  β-lactam and β-lactamase inhibitor combinations in the treatment of extended-spectrum β-lactamase producing Enterobacteriaceae: time for a reappraisal in the era of few antibiotic options? , 2015, The Lancet. Infectious diseases.

[21]  J. Cruzado,et al.  Risk Factors and Outcomes of Bacteremia Caused by Drug-Resistant ESKAPE Pathogens in Solid-Organ Transplant Recipients , 2013, Transplantation.

[22]  F. Cosio,et al.  Urinary tract infections in kidney transplant recipients: role of gender, urologic abnormalities, and antimicrobial prophylaxis. , 2013, Annals of transplantation.

[23]  E. Krenzelok,et al.  The effects of penicillin and cephalosporin ingestions in children less than six years of age. , 1988, Veterinary and human toxicology.