Efficacy of Cefoperazone-Sulbactam versus Meropenem in the management of gram- negative complicated and uncomplicated Pyelonephritis: a 17-year retrospective cohort study at a tertiary care hospital in Karachi

Abstract

Background: Pyelonephritis, a severe bacterial infection of the kidney, poses significant
morbidity risks, specifically when complicated. The Gram –ve pathogens, often multidrug-
resistant, drive the requirement for effective empiric antibiotics like cefoperazone-sulbactam
(CSZ) and meropenem (MEM).
Objective: This study compares CSZ versus MEM in managing complicated versus
uncomplicated pyelonephritis, evaluating key outcomes including mortality, clinical failure, ICU
admissions, and hospital stay.
Methods: A comparative, retrospective comparative cohort, conducted on adult patients
hospitalized with culture-confirmed gram-negative pyelonephritis (complicated n=92,
uncomplicated n=69) from May 2025 to November 2025 at Department of Infectious Diseases of
Indus Hospital and Health Network (IHHN) Korangi Campus. Cases received either CSZ (2–4 g
IV q8–12h) or MEM (1 g IV q8h), as per local guidelines and clinician discretion. Patient’s
outcomes included 30-day mortality, early clinical failure (within 72h), ICU admission, re-
hospitalization, and hospital length-of-stay. Data were extracted from hospital records, ana
analyzed by using SPSS version 26.
Results: Mena age of patients in the CSZ group was 45.7 years and 51.1 years in the MEM
group. Females were most common 119 (73.5%) compared to males (26.5%). Complicated
pyelonephritis was present in 4 patients (6.0%) in the CSZ group versus 15 patients (15.8%) in
the MEM group. The mean SOFA score was 2.3 in the CSZ group and 3.7 in the MEM group (p
= 0.001). ICU admission was required in 4 patients (6.0%) in the CSZ group compared with 15
patients (15.8%) in the MEM group (p = 0.025), reflecting the higher proportion of clinically
severe cases in the Meropenem arm. Mean length of hospital stay was 9.2 days in the CSZ group
and 11.5 days in the MEM group. All-cause mortality was recorded in 1 patient (1.5%) in the
CSZ group and 4 patients (4.3%) in the MEM group and this did not reach statistical significance
(p=0.87). Early clinical failure in terms of absence of clinical improvement within 72 hours of
antibiotic initiation occurred in 4 of 65 evaluable patients (6.2%) in the CSZ group and 10 of 94
patients (10.6%) in the MEM group, without statistical significance (p = 0.78). Clinical non-
response at the end of the treatment period was documented in 2 of 66 patients (3.0%) receiving
CSZ and 4 of 94 patients (4.3%) receiving MEM. The microbiological failure in terms of
persistence of the causative organism on repeat urine culture was higher CSZ group compared to
MEM group, (p = 0.95). The need for escalation to an alternative or additional antibiotic due to
clinical deterioration or treatment failure occurred in 3 patients (4.5%) in the CSZ group and 4
patients (4.3%) in the MEM group. Moreover in complicated pyelonephritis (CSZ n=38 vs.
MEM n=54), (CSZ) showed numerically superior outcomes, including lower mortality (2.6% vs.
7.4%), early failure (10.8% vs. 16.7%), ICU admissions (10.5% vs. 25.9%), and shorter hospital
stay (10.8 vs. 13.2 days), though differences were non-significant due to small samples, while in
uncomplicated pyelonephritis, both arms yielded excellent, equivalent results (p>0.05).
Conclusion: The CSZ showed comparable efficacy to Meropenem in treating gram-negative
pyelonephritis, with numerically superior outcomes in complicated cases. However in
uncomplicated pyelonephritis, both agents achieved excellent, equivalent effectiveness. CSZ
offers a compelling alternative to carbapenems, promoting antimicrobial stewardship, reducing

costs, and simplifying dosing without compromising safety. Prospective, adequately powered
RCTs are recommended to confirm these findings and guide guidelines.