A Review: Effectiveness of Cephalosporins/Siderophore Cephalosporins versus Meropenem as Therapy in Patients with Hospital Acquired Pneumonia

Palevi Ruflianasari; Tri Murti Andayani; Dwi  Endarti

doi:10.30595/jhepr.v3i1.158

Authors

Palevi Ruflianasari Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia
Tri Murti Andayani Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia
Dwi Endarti Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia

DOI:

https://doi.org/10.30595/jhepr.v3i1.158

Keywords:

Hospital Acquired Pneumonia, meropenem, cephalosporin, nosocomial pneumonia

Abstract

Background: Hospital-Acquired Pneumonia (HAP) is a nosocomial infection that causes mortality and morbidity. It also leads to increased length of hospitalization and cost of care. Increasing antibiotic resistance necessitates the search for alternative antibiotics, such as HAP therapy. Carbapenem antibiotics as standard HAP antibiotics and cephalosporins/cephalosporin siderophores have proven effective for infections caused by gram-negative bacteria that cause HAP. This review aimed to evaluate the combination of cephalosporins and beta-lactamase inhibitors as an effective therapy for HAP that can reduce the risk of antibiotic resistance.

Methods: Cochrane and PubMed were the sources for searching articles in this study. The articles were then selected by using the PICO method (Population, Intervention, Comparison, and Outcomes). The target population was adult HAP patients, with interventions of cefiderocol, ceftazidime-avibactam, and ceftolozane-tazobactam. The comparator in this study was meropenem, and the outcome was clinical improvement with microbiological response and mortality as the parameters. The PRISMA flow chart later described a summation of this review study.

Results: Eight articles comprehensively discussed the effectiveness of cephalosporins/siderophore cephalosporins and meropenem against Klebsiella pneumonia, Pseudomonas aeruginosa, and Escherichia coli. The clinical recovery of patients after administering these two antibiotics showed high therapeutic effectiveness and could reduce mortality. Ceftazidime-avibactam, ceftolozane-tazobactam, and cefiderocol are new antibiotics that are effective for HAP. Meropenem at high doses can offset the efficacy of the three antibiotic combinations and minimize antibiotic resistance.

Conclusion: Meropenem and cephalosporins/siderophore cephalosporins have similar effectiveness as therapy for gram-negative infections in HAP, with attention to dosage to obtain effective therapy.

Keywords: Cephalosporins, Hospital Acquired Pneumonia, Meropenem, Nosocomial Pneumonia.

References

Hospital-Acquired Pneumonia (Nosocomial Pneumonia) and Ventilator-Associated Pneumonia: Overview, Pathophysiology, Etiology. (2023).

Liu, J.-W. et al. Randomized Noninferiority Trial of Cefoperazone-Sulbactam versus Cefepime in the Treatment of Hospital-Acquired and Healthcare-Associated Pneumonia. Antimicrob Agents Chemother 63, e00023-19 (2019).

Azmi, S. et al. Assessing the burden of pneumonia using administrative data from Malaysia, Indonesia, and the Philippines. International Journal of Infectious Diseases 49, 87–93 (2016).

Kalil, A. C. et al. Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clinical Infectious Diseases 63, e61–e111 (2016).

Bui, T. & Preuss, C. V. Cephalosporins. in StatPearls (StatPearls Publishing, Treasure Island (FL), 2023).

Nicolau, D. P. Carbapenems: a potent class of antibiotics. Expert Opin Pharmacother 9, 23–37 (2008).

Syed, Y. Y. Cefiderocol: A Review in Serious Gram-Negative Bacterial Infections. Drugs 81, 1559–1571 (2021).

Bassetti, M. et al. Efficacy and safety of cefiderocol or best available therapy for the treatment of serious infections caused by carbapenem-resistant Gram-negative bacteria (CREDIBLE-CR): a randomised, open-label, multicentre, pathogen-focused, descriptive, phase 3 trial. The Lancet Infectious Diseases 21, 226–240 (2021).

Matsunaga, Y. et al. 1292. Safety Profile of the Novel Siderophore Cephalosporin Cefiderocol in Randomized Phase 2 and Phase 3 Clinical Studies of Serious Gram-Negative Infections. Open Forum Infectious Diseases 7, S661–S662 (2020).

Plaisance, C. J. et al. Cefiderocol (Fetroja) as a Treatment for Hospital-Acquired Pneumonia. Cureus 16, e52230.

Bilal, M. et al. Clinical Pharmacokinetics and Pharmacodynamics of Cefiderocol. Clin Pharmacokinet 60, 1495–1508 (2021).

Wunderink, R. G. et al. Cefiderocol versus high-dose, extended-infusion meropenem for the treatment of Gram-negative nosocomial pneumonia (APEKS-NP): a randomised, double-blind, phase 3, non-inferiority trial. The Lancet Infectious Diseases 21, 213–225 (2021).

Matsunaga, Y. et al. Efficacy of Cefiderocol in Severely Ill Nosocomial Pneumonia Patients in APEKS-NP Study. in B28. HOST AND MICROBIAL CLINICAL STUDIES IN LUNG INFECTIONS AND LUNG DISEASES A2951–A2951 (American Thoracic Society, 2020). doi:10.1164/ajrccm-conference.2020.201.1_MeetingAbstracts.A2951.

Viale, P., Sandrock, C. E., Ramirez, P., Rossolini, G. M. & Lodise, T. P. Treatment of critically ill patients with cefiderocol for infections caused by multidrug-resistant pathogens: review of the evidence. Ann. Intensive Care 13, 52 (2023).

Rup, A. R., Dash, A. K. & Patnaik, S. Ceftazidime-Avibactam for Hospital Acquired Pneumonia Due to Extended Drug-Resistant Klebsiella pneumoniae. Indian J Pediatr 88, 290–291 (2021).

Torres, A. et al. Randomized Trial of Ceftazidime-Avibactam vs Meropenem for Treatment of Hospital-Acquired and Ventilator-Associated Bacterial Pneumonia (REPROVE): Analyses per US FDA–Specified End Points. Open Forum Infectious Diseases 6, (2019).

Torres, A. et al. Ceftazidime-avibactam versus meropenem in nosocomial pneumonia, including ventilator-associated pneumonia (REPROVE): a randomised, double-blind, phase 3 non-inferiority trial. The Lancet Infectious Diseases 18, 285–295 (2018).

Chen, Y., Huang, H.-B., Peng, J.-M., Weng, L. & Du, B. Efficacy and Safety of Ceftazidime-Avibactam for the Treatment of Carbapenem-Resistant Enterobacterales Bloodstream Infection: a Systematic Review and Meta-Analysis. Microbiology Spectrum 10, (2022).

Zhuang, H.-H. et al. Efficacy and mortality of ceftazidime/avibactam-based regimens in carbapenem-resistant Gram-negative bacteria infections: A retrospective multicenter observational study. Journal of Infection and Public Health 16, 938–947 (2023).

Shirley, M. Ceftazidime-Avibactam: A Review in the Treatment of Serious Gram-Negative Bacterial Infections. Drugs 78, 675–692 (2018).

Das, S. et al. Selecting the dosage of ceftazidime–avibactam in the perfect storm of nosocomial pneumonia. Eur J Clin Pharmacol 76, 349–361 (2020).

Martin-Loeches, I. et al. Clinical and microbiological outcomes, by causative pathogen, in the ASPECT-NP randomized, controlled, Phase 3 trial comparing ceftolozane/tazobactam and meropenem for treatment of hospital-acquired/ventilator-associated bacterial pneumonia. Journal of Antimicrobial Chemotherapy 77, 1166–1177 (2022).

Montero, M. et al. Efficacy of Ceftolozane-Tazobactam in Combination with Colistin against Extensively Drug-Resistant Pseudomonas aeruginosa, Including High-Risk Clones, in an In Vitro Pharmacodynamic Model. Antimicrobial Agents and Chemotherapy 64, (2020).

Zhang, Z. et al. Population Pharmacokinetic Analysis for Plasma and Epithelial Lining Fluid Ceftolozane/Tazobactam Concentrations in Patients With Ventilated Nosocomial Pneumonia. The Journal of Clinical Pharma 61, 254–268 (2021).

Kollef, M. H. et al. Ceftolozane–tazobactam versus meropenem for treatment of nosocomial pneumonia (ASPECT-NP): a randomised, controlled, double-blind, phase 3, non-inferiority trial. The Lancet Infectious Diseases 19, 1299–1311 (2019).

Huntington, J. A. et al. Outcomes in Participants with Renal Impairment from a Phase 3 Clinical Trial for Ceftolozane/Tazobactam Treatment of Nosocomial Pneumonia (ASPECT-NP). Antimicrob Agents Chemother 64, e00731-20 (2020).

Zhanel, G. G. et al. Ceftolozane/tazobactam: a novel cephalosporin/β-lactamase inhibitor combination with activity against multidrug-resistant gram-negative bacilli. Drugs 74, 31–51 (2014).