Comparative Outcomes of Meropenem and Imipenem in Multidrug-Resistant Pulmonary Infections: A Prospective Cohort Study

Summary

The present protocol describes that Meropenem and Imipenem show comparable pathogen clearance; however, Meropenem demonstrates faster symptom relief, improved lung function, reduced inflammatory markers, and fewer adverse effects, indicating its potential as a safer and more effective first-line therapy for MDR pulmonary infections.

Abstract

Pulmonary infections due to multidrug-resistant (MDR) organisms (MDRO) pose a significant global public health challenge due to their high mortality rates and complex management. Carbapenem antibiotics, including Meropenem and Imipenem, are cornerstone therapies for MDR Gram-negative bacterial infections, with their efficacy and safety critically influencing patient outcomes. In this prospective cohort study, we compared the day-7 pathogen clearance rates of Meropenem and Imipenem in MDR bacterial pulmonary infections and also evaluated prespecified secondary clinical and safety outcomes. For the primary endpoint, no statistically significant difference was observed between the two groups in day-7 pathogen clearance (P>0.05). However, supportive secondary analyses showed that the meropenem group had shorter observed times to resolution of cough, sputum production, lung rales, and fever (P<0.05). In addition, meropenem-treated patients showed greater improvement in selected lung function parameters, a more pronounced reduction in PaCO₂ (P<0.05), lower post-treatment PCT and hs-CRP levels (P<0.05), and fewer reported adverse events (P<0.05). These observational findings suggest that Meropenem may offer clinical advantages in MDRO-induced pulmonary infections, although the results should be interpreted in the context of the non-randomized study design.

Introduction

Multidrug-resistant (MDR) organism (MDRO)-induced pulmonary infections pose a significant global public health challenge¹. In recent years, the increasing prevalence of MDROs (e.g., carbapenem-resistant Enterobacteriaceae, Acinetobacter baumannii) has been driven by factors such as antibiotic overuse, nosocomial transmission, and bacterial evolution². The World Health Organization reports that infections with MDR strains are associated with higher mortality rates compared to susceptible strains, particularly in intensive care units (ICUs), where treatment complexity and healthcare costs present substantial clinical burdens³. Carbapenems, including Meropenem and Imipenem, have traditionally been first-line agents for MDRO-associated infections due to their broad-spectrum efficacy against Gram-negative bacteria⁴. However, the emergence and spread of carbapenem resistance mechanisms (e.g., KPC and NDM-1 enzymes) have compromised their clinical utility, and how to optimize their clinical application has become the research focus^5,6.

Current research comparing the effectiveness of Meropenem and Imipenem primarily examines clinical response rates, adverse events, and bacterial eradication rates. For instance, evidence suggests that Meropenem demonstrates superior efficacy in treating central nervous system infections due to its enhanced penetration of the blood-brain barrier⁷. In contrast, Imipenem exhibits slightly greater in vitro activity against certain strains of Pseudomonas aeruginosa, though its clinical utility is constrained by potential nephrotoxicity and neurotoxicity⁸. Meanwhile, existing studies also reveal considerable variability in reported pathogen clearance rates. This inconsistency stems from divergent definitions and assessment timelines for "clearance" across trials, as well as variations in pathogen characteristics (e.g., enzyme-producing vs. non-enzyme-producing strains), infection severity, and patient comorbidities, all of which complicate generalizability. Furthermore, few investigations conduct subgroup analyses focusing on MDROs, creating a gap in evidence for clinical decision-making^9,10. Accordingly, the clinical question addressed in this study was whether Meropenem and Imipenem differ in comparative microbiological and clinical outcomes in patients with MDRO-associated pulmonary infection.

Consequently, this study specifically examined patients with MDRO-induced bacterial pulmonary infections and directly compared Meropenem with Imipenem. The primary objective was to compare day-7 pathogen clearance between the two treatment groups, while secondary analyses evaluated symptom recovery, pulmonary function, inflammatory markers, and adverse events. Because treatment responses may vary according to pathogen distribution and clinical context, these additional analyses were intended to provide supportive clinical information for carbapenem selection.

Protocol

This study was approved by the Ethics Committee of Nantong Third People’s Hospital (Approval No. 2025NG023). Written informed consent was obtained from all participants prior to enrollment. All procedures were conducted in accordance with the principles of the Declaration of Helsinki and institutional ethical guidelines. The reagents and the equipment used are listed in the Table of Materials.

1. Research subjects
The potential research participants were MDRO-induced pulmonary infection patients hospitalized between March 2024 and January 2025. The required sample size was calculated using G*Power software, followed by participant selection based on inclusion and exclusion criteria (see Figure 1 for the detailed selection process). Ultimately, 112 eligible participants were enrolled, with 59 assigned to the Meropenem group for Meropenem treatment and 53 to the Imipenem group for Imipenem therapy. Treatment allocation was clinician-driven and reflected routine prescribing decisions made by the treating physicians at the time of carbapenem initiation. All participants provided written informed consent, and they were unaware of their group allocation. Treating physicians and the research staff responsible for outcome collection were not blinded because treatment allocation determined the administered carbapenem regimen. To reduce assessment bias, outcome definitions were prespecified, and laboratory as well as microbiological results were obtained from routine hospital records.

1. Inclusion and exclusion criteria
   Inclusion Criteria: Confirmed diagnosis of MDRO-induced infections based on baseline respiratory specimen culture before carbapenem initiation¹¹; Initiation of carbapenem monotherapy within 48 h of admission, with no prior exposure to similar antibiotics; Completion of ≥7 days of therapy and microbiological assessment on day 7 post-treatment.
   Exclusion Criteria: Primary infections caused by Gram-positive bacteria or fungi; Life expectancy <72 h; Pregnancy or lactation; Defective clinical records.
   Antimicrobial susceptibility testing was performed on the baseline isolates as part of routine clinical microbiology using automated susceptibility testing, and the results, including meropenem and imipenem MIC values, were interpreted according to CLSI criteria.

2. Treatment methods

1. Meropenem group
   Patients received intravenous Meropenem at 0.5 g or 1.0 g every 8 h (with an initial 1 g loading dose), with dose selection based on the treating physician's assessment of renal function, infection severity, and routine institutional prescribing practice. Each infusion lasted at least 30 min. Treatment duration was initially set at 7–14 days, adjusted based on clinical response, and continued for 3–5 days after fever resolution and inflammatory marker normalization. Combination therapy with anti-Pseudomonas aeruginosa agents (e.g., ciprofloxacin) or anti-MRSA drugs (e.g., vancomycin) was permitted, but Meropenem remained the primary therapeutic agent.
2. Imipenem group
   Patients were given Imipenem intravenously at 0.5 g per dose (with a 1 g initial loading dose) every 8 h, infused over ≥30 min. The treatment duration and combined medication protocols were the same as above. The use of concomitant antibiotics was recorded for each patient and categorized as adjunctive anti-Pseudomonal therapy, adjunctive anti-MRSA therapy, or other concomitant antibacterial therapy for between-group comparison.
   Beta-lactamase inhibitor-containing regimens were not incorporated into the study protocol because the aim of the present study was to compare Meropenem and Imipenem themselves as the principal carbapenem regimens used in routine practice during the study period. Patients who required upfront treatment with novel beta-lactam/beta-lactamase inhibitor combinations were outside the predefined treatment framework of this analysis.

3. Endpoints

1. Primary outcome measures
   The primary endpoint was the pathogen clearance rate, defined as two consecutive negative bacterial cultures of respiratory specimens (collected 24 h apart) by the seventh day after treatment initiation.
2. Secondary outcomes
   (1) The study recorded the time from treatment initiation to the resolution of cough, sputum production, lung rales, and fever. (2) Pulmonary function was assessed using spirometry to measure FVC and FEV1, with the FEV1/FVC ratio calculated. Spirometry was performed when patients were clinically stable enough to cooperate, once before treatment initiation and again after completion of the treatment course. Testing followed routine standardized pulmonary function procedures in the hospital or ATS/ERS-based procedures, if applicable. If a measurement was incomplete or did not meet acceptability criteria, the test was repeated when feasible; otherwise, the corresponding value was treated as missing for paired analysis. Arterial blood gas analysis was also performed to determine PaO₂ and PaCO₂ levels before and after treatment. (3) Fasting venous blood samples were collected pre- and post-treatment and divided into two portions. One portion was used for liver and kidney function parameter (ALT, AST, BUN, Scr) measurements using an automated biochemical analyzer. The other was subjected to ELISA assessments of inflammatory markers (SAA, IL-6, IL-17A, PCT, hs-CRP) using standardized kits, following manufacturer protocols. These biomarker analyses were prespecified secondary outcomes. SAA and hs-CRP were included as markers of systemic inflammatory response, PCT as a marker related to bacterial infection burden, and IL-6 and IL-17A to reflect cytokine-mediated inflammatory activation. (4) Adverse events occurring during treatment were monitored through daily clinical assessment, symptom inquiry, and routine laboratory review.

4. Statistical methods
Statistical analysis was conducted with SPSS 24.0. Categorical variables were expressed as frequencies and percentages [n(%)] and analyzed using χ² tests. For continuous variables, normality was assessed by the Shapiro-Wilk test. Normally distributed data (presented as mean ± standard deviation) were compared using independent or paired t-tests, while non-normally distributed data [expressed as median (interquartile range)] were analyzed with non-parametric Mann-Whitney U or Wilcoxon signed-rank tests. P-values <0.05 denoted the presence of statistically significant differences.

Results

Clinical data comparison
The baseline characteristics, including demographic variables, major clinical features, microbiological profile, and baseline carbapenem susceptibility data, were compared between the groups. The analysis revealed no statistically significant differences (P>0.05), indicating comparable baseline profiles (Table 1).

Primary endpoint: Similar Day-7 pathogen clearance between groups
For the primary endp...

Discussion

MDRO-induced pulmonary infections pose a significant challenge in critical care medicine worldwide due to their high mortality rates and complex treatment requirements¹². This study is the first to prospectively compare the pathogen clearance efficacy of Meropenem and Imipenem in patients with MDRO lung infections. The findings revealed no statistically significant difference in pathogen eradication between the two groups. However, the meropenem group demonstrated superior outcomes in clinical sym...

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Antimicrobial Susceptibility Test Card	bioMérieux, France	Compatible with VITEK 2 Compact	Compatible with automated antimicrobial susceptibility testers, determining the MIC values of strains to drugs such as meropenem and imipenem
Arterial Blood Gas Analyzer	Radiometer, Denmark	ABL800	Used to detect partial pressure of oxygen (PaO2) and partial pressure of carbon dioxide (PaCO2) in patient arterial blood, evaluating pulmonary gas exchange function
Automated Antimicrobial Susceptibility Tester	bioMérieux, France	VITEK 2 Compact	Used for antimicrobial susceptibility testing of bacteria isolated from baseline respiratory specimens; MIC results interpreted according to CLSI standards
Automated Biochemical Analyzer	Hitachi, Japan	Hitachi 7600	Used to detect liver and kidney function indicators (ALT, AST, BUN, Scr) in patient serum, providing data for clinical safety assessment
Blood Agar Medium	Hangzhou Microbial Reagent Co., Ltd., China	CM115	Used for bacterial isolation and pure culture of respiratory specimens, providing strains for MDRO identification and antimicrobial susceptibility testing
Ciprofloxacin Injection	Bayer Healthcare Co., Ltd., China	0.2g Specification	Adjuvant therapeutic medication, used for combined antimicrobial treatment of patients with Pseudomonas aeruginosa co-infection
Clot-Activator Blood Collection Tube	Shandong Weigao Group Medical Polymer Products Co., Ltd., China	3.5mL Specification	Used for collecting fasting venous blood, separating serum for liver and kidney function testing and inflammatory marker detection
ELISA Detection Kit (hs-CRP)	R&D Systems, USA	DY2915	Quantitatively detects high-sensitivity C-reactive protein concentration in patient serum, evaluating the degree of systemic inflammatory response
ELISA Detection Kit (IL-17A)	R&D Systems, USA	DY317	Quantitatively detects interleukin-17A concentration in patient serum, evaluating the level of cytokines related to inflammatory response
ELISA Detection Kit (IL-6)	R&D Systems, USA	DY206	Quantitatively detects interleukin-6 concentration in patient serum, reflecting the degree of cytokine-mediated inflammatory activation
ELISA Detection Kit (PCT)	R&D Systems, USA	DY1758	Quantitatively detects procalcitonin concentration in patient serum, reflecting the burden of bacterial infection
ELISA Detection Kit (SAA)	R&D Systems, USA	DY1827	Quantitatively detects serum amyloid A concentration in patient serum, reflecting systemic inflammatory response of the body
G*Power software	Heinrich Heine University Düsseldorf, Germany	https://www.psychologie.hhu.de/arbeitsgruppen/allgemeine-psychologie-und-arbeitspsychologie/gpower	G*Power is a  statistical software used for a priori and post hoc power analysis and sample size estimation for common parametric and nonparametric tests.
High-Speed Refrigerated Centrifuge	Xiangyi Laboratory Instrument Development Co., Ltd., China	TDZ5-WS	Used to separate fasting venous blood samples, achieving separation of serum and blood cells, and providing samples for subsequent biochemical and ELISA testing
Imipenem Injection	Merck & Co., Inc., USA	0.5g Specification	Control group medication; administered intravenously at a dose of 0.5g every 8 hours, with an initial loading dose of 1g and an infusion time ≥30 minutes
Lithium Heparin Anticoagulant Blood Collection Tube	Shandong Weigao Group Medical Polymer Products Co., Ltd., China	3mL Specification	Used for collecting arterial/venous blood, for arterial blood gas analysis testing, preventing blood coagulation
Liver and Kidney Function Test Kit (ALT/AST)	Sinobiological Beikong Biotechnology Co., Ltd., China	Compatible with Hitachi 7600/20240205	Uses colorimetry to detect alanine transaminase and aspartate transaminase in serum, evaluating liver function status
Liver and Kidney Function Test Kit (BUN/Scr)	Sinobiological Beikong Biotechnology Co., Ltd., China	Compatible with Hitachi 7600	Uses rate method to detect blood urea nitrogen and serum creatinine in serum, evaluating renal function status
MacConkey Agar Medium	Hangzhou Microbial Reagent Co., Ltd., China	CM106	Used for isolation and preliminary identification of Gram-negative bacteria, screening pathogenic bacteria in respiratory specimens
Meropenem Injection	Hengrui Pharmaceutical Co., Ltd., China	0.5g/1.0g Specification	Study group medication; administered intravenously at a dose of 0.5g/1.0g every 8 hours, with an initial loading dose of 1g and an infusion time ≥30 minutes
Microplate Reader	Thermo Fisher Scientific, USA	Multiskan FC	Used with ELISA kits to detect absorbance values of inflammatory markers in serum and quantitatively analyze concentrations of indicators such as SAA and IL-6
Pipette	Eppendorf, Germany	Research plus	Used for precise pipetting in ELISA experiments and sample processing, ensuring the accuracy of experimental operations
Pulmonary Function Tester (Spirometer)	Jaeger, Germany	MasterScreen PFT	Used to detect pulmonary function indicators such as forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) in patients, following ATS/ERS standardized operating procedures
SPSS Statistical Software	IBM Corporation, USA	24	Used for statistical analysis of all data in the study, including chi-square test, t-test, nonparametric test, etc.
Vancomycin Injection	Eli Lilly and Company, USA	0.5 g Specification	Adjuvant therapeutic medication, used for combined antimicrobial treatment of patients with methicillin-resistant Staphylococcus aureus (MRSA) co-infection