Antibiotics for complicated urinary tract infection and acute pyelonephritis: A systematic review

Table 1 Key studies of antibiotic therapy for complicated urinary tract infections and pyelonephritis

Ref.	Study design	Population	Therapy	Findings
Park et al[7], 2014	Observational study	152 patients with pyelonephritis caused by ESBL-producing Escherichia coli	Carbapenems for median 12 d vs non-carbapenems for median 8 d	Clinical failure was similar between the two groups (weighted HR: 1.05)
Wagenlehner et al[8], 2016	RCT	1033 with suspected or confirmed cUTI/APN, randomized 1:1 to each arm	Ceftazidime-avibactam vs doripenem up to 10 d or 14 d for patients with bacteremia	Microbiological eradication rate: 77.4% ceftazidime-avibactam; 71.0% doripenem
Ren et al[9], 2017	TCT	330 patients diagnosed with cUTI or APN, randomized 1:1 to each arm	IV levofloxacin 750 mg for 5 d vs IV levofloxacin 500 mg and shift to oral levofloxacin 500 mg for 7-14 d	Clinical success rate: 89.87% in IV levofloxacin 750 mg vs 89.31% in IV/oral levofloxacin 50 vs 0 mg
Kaye et al[10], 2018	RCT	550 patients with cUTI or APN, randomized 1:1 to each arm	Meropenem-vaborbactam vs piperacillin-tazobactam for 10 d	Clinical success rate: 98.4% in the meropenem-vaborbactam group vs 95.6% in the piperacillin-tazobactam group
Connolly et al[11], 2018	RCT	145 patients diagnosed with cUTI and APN, randomized at 22, 76 and 47 in each arm	Plazomicin at 10 mg/kg vs plazomicin at 15 mg/kg vs levofloxacin 750 mg for 5 d	Microbiological eradication rate in MITT and MIE population: 50.0% and 85.7% (plazomicin at 10 mg/kg) vs 60.8% and 88.6% (plazomicin at 15 mg/kg) vs 58.6% and 81.0% (levofloxacin)
Rudrabhatla et al[12], 2018	RCT	54 patients diagnosed with APN, randomized 1:1 to each arm	Non-fluoroquinolone antibiotics for 7 d vs 14 d	Patients who received antibiotics for 7 d had shorter hospital stay (8 d vs 14 d) and less antibiotic consumption (8.4 DDs vs 17.4 DDs) No patients required retreatment
Arakawa et al[13], 2018	Non-randomized, trial	115 patients diagnosed with pyelonephritis or complicated cystitis	IV tazobactam-ceftolozane every 8 h for 7 d	Clinical response rate was 96.6%
Ryanto et al[14], 2019	Observational study	152 patients diagnosed with severe pyelonephritis/urosepsis	Gentamicin was prescribed for 43.4% patients; 32% of patients were given initial dosing of gentamicin	Duration of IV, time of resolution, and length of stay is short in patients given gentamicin; initial dose of IV gentamicin improved the outcome of patients

APN: Acute pyelonephritis; cUTI: Complicated urinary tract infection; DD: Daily dose; ESBL: Extended-spectrum -lactamase; HR: Hazard ratio; IV: Intravenous; ME: Microbiologically evaluable; MITT: Modified intent-to-treat; RCT: Randomized control trial.

Table 2 Adverse events associated with antibiotic therapy reported in the studies

Antibiotics	Ref.	Adverse events reported	Most common adverse effects	Frequency, n/total (%)
Ceftazidime-avibactam	Wagenlehneret al[8]	Headache, nausea, diarrhea, constipation	Headache	185/511 (36.2)
Doripenem	Wagenlehneret al[8]	Headache, nausea, diarrhea, constipation	Headache	158/509 (31.0)
Levofloxacin	Ren et al[9]	Reduction in leukocyte count, reduction in neutrophil count, increased ALT, increased AST, increased platelet count, increased blood pressure, gastrointestinal, reaction at injection site, cutaneous/subcutaneous, nervous system/mental, immune, infection, hepatobiliary, metabolic/nutritional, musculoskeletal/connective tissue	Reduction in leukocyte count and gastrointestinal	109/329 (33.1)
	Connolly et al[11]	Headache, diarrhea, vomiting, nausea, dizziness	Headache	21/44 (47.7)
Meropenem-vaborbactam	Kaye et al[10]	Headache, diarrhea, nausea, asymptomatic bacteriuria, catheter site phlebitis, infusion site phlebitis, urinary tract infection, hypokalemia, vaginal infection, ALT increased, anemia, AST increased, pyrexia	Headache	106/272 (39.0)
Piperacillin-tazobactam	Kaye et al[10]	Headache, diarrhea, nausea, asymptomatic bacteriuria, catheter site phlebitis, infusion site phlebitis, urinary tract infection, hypokalemia, vaginal infection, ALT increased, anemia, AST increased, pyrexia, dyspnea	Headache	97/273 (35.5)
Plazomicin	Connolly et al[11]	Headache, diarrhea, vomiting, nausea, dizziness	Headache	33/96 (34.4)
Tazobactam-ceftolozane	Arakawa et al[13]	Diarrhea, ALT increased, constipation, AST increased, insomnia, headache, pyelonephritis, pyelonephritis acute, contusion, viral upper respiratory tract infection	Diarrhea and ALT increased	20/114 (17.5)

ALT: Alanine aminotransferase; AST: Aspartate aminotransferase.