What is the preferred treatment for multidrug-resistant (MDR) Klebsiella pneumoniae in sputum, Meropenem versus Ceftazidime/Avibactam (Ceftazidime/Avibactam)?

From the Guidelines

For the treatment of sputum Klebsiella mdr, ceftazidime/avibactam is recommended over meropenem due to its efficacy against KPC-producing CRE infections, as supported by observational studies and real-world experience 1. When considering the treatment options, the following factors should be taken into account:

• The strength of recommendation for ceftazidime/avibactam is strong, with a moderate certainty of evidence 1
• Ceftazidime/avibactam has been shown to have a higher clinical cure rate and lower mortality compared to traditional antibiotic regimens, including meropenem, in patients with KPC-producing CRE infections 1
• Meropenem/vaborbactam may be considered as an alternative, especially in cases of pneumonia, due to its high epithelial lining fluid (ELF) concentrations and intrapulmonary penetration ratios 1
• Local epidemiology and the emergence of ceftazidime/avibactam resistance in KPC-producing isolates should also be considered when choosing between ceftazidime/avibactam and meropenem/vaborbactam 1
• Imipenem/relebactam and cefiderocol may also be considered as potential alternatives, although clinical studies of their efficacy in KPC-producing CRE infections are limited 1 The dosing of ceftazidime/avibactam is typically 2.5g (2g ceftazidime/0.5g avibactam) IV every 8 hours, with dose adjustments needed for renal impairment. Some key points to consider when treating sputum Klebsiella mdr include:
• The importance of culture and susceptibility results to guide treatment
• The need for de-escalation to narrower therapy when possible
• The monitoring of clinical response through symptom improvement, inflammatory marker trends, and follow-up cultures if appropriate
• The consideration of patient factors such as renal function and previous antibiotic exposure when choosing a treatment option.

From the FDA Drug Label

AVYCAZ (ceftazidime and avibactam) is indicated for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) in adult and pediatric patients (at least 31 weeks gestational age) caused by the following susceptible gram-negative microorganisms: Klebsiella pneumoniae AVYCAZ (ceftazidime and avibactam) in combination with metronidazole, is indicated for the treatment of complicated intra-abdominal infections (cIAI) in adult and pediatric patients (at least 31 weeks gestational age) caused by the following susceptible gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae

The choice between Meropenem and Ceftazidime-Avibactam for the treatment of sputum Klebsiella multi-drug resistant (MDR) infections depends on various factors, including local susceptibility patterns and the specific resistance profile of the isolate.

• Ceftazidime-Avibactam is effective against Klebsiella pneumoniae, including some strains that produce certain beta-lactamases 2.
• However, the drug label does not provide direct information on the comparative effectiveness of Meropenem versus Ceftazidime-Avibactam for this specific indication. Given the lack of direct comparative data in the label, it is not possible to draw a conclusion about which drug is more effective for the treatment of sputum Klebsiella MDR infections.

From the Research

Sputum Klebsiella MDR Treatment Options

• Meropenem and ceftazidime/avibactam are two potential treatment options for multidrug-resistant (MDR) Klebsiella pneumoniae infections.
• A study published in 2024 3 found that the combination of ceftazidime/avibactam and meropenem showed remarkable synergistic activity against 26 KPC-producing K. pneumoniae strains and restored susceptibility to both partnering antibiotics.

Comparison of Ceftazidime/Avibactam and Meropenem

• Ceftazidime/avibactam has been shown to be effective against MDR Gram-negative bacteria, including K. pneumoniae, with a spectrum of inhibition of class A and C β-lactamases, including ESBLs, AmpC, and KPC enzymes 4.
• Meropenem, on the other hand, is a carbapenem antibiotic that has been used to treat various infections, including those caused by MDR bacteria.
• A study published in 2023 5 found that ceftazidime/avibactam and meropenem-vaborbactam were highly active against MDR Enterobacterales, with identical susceptibility rates of 97.9%.

Combination Therapy

• Combination therapy with ceftazidime/avibactam and meropenem may be a viable option for treating serious infections caused by KPC-producing K. pneumoniae, as it has been shown to have synergistic activity and prevent the emergence of resistance mutations 3.
• Another study published in 2025 6 found that the combination of ceftazidime/avibactam and aztreonam was effective against MBL-producing K. pneumoniae, with 62.5% of isolates shifting from resistance to sensitivity.

Mechanisms of Resistance

• K. pneumoniae is a nosocomial pathogen that is commonly implicated in hospital outbreaks and has a propensity for antimicrobial resistance toward mainstay β-lactam antibiotics and multiple other antibiotic classes 7.
• Understanding the mechanisms of resistance is crucial for improving the efficacy of current antimicrobials and designing novel therapeutic agents that can circumvent these mechanisms.