What antibiotics are effective against Klebsiella pneumoniae?

From the Guidelines

For the treatment of Klebsiella pneumoniae infections, particularly those caused by carbapenem-resistant Enterobacteriaceae (CRE), ceftazidime/avibactam and meropenem/vaborbactam are strongly recommended as first-line treatment options due to their efficacy and safety profiles, as evidenced by recent studies 1. The choice between these two options may depend on the site of infection, with meropenem/vaborbactam potentially being preferred for infections such as pneumonia due to its pharmacokinetic/pharmacodynamic properties 1. Other options like imipenem/relebactam and cefiderocol may also be considered, especially in cases where the first-line options are not suitable, although the evidence for these alternatives is less robust 1, 2. It's crucial to note that the emergence of resistance, including to ceftazidime/avibactam, should be monitored, and local epidemiology should guide the selection of antibiotics 1. In the context of metallo-β-lactamase (MBL)-producing CRE, the combination of ceftazidime/avibactam plus aztreonam is recommended, with cefiderocol being a potential alternative 2. Ultimately, treatment decisions should be made based on the most current and highest-quality evidence available, considering factors such as the specific resistance pattern of the isolate, the site and severity of the infection, and the patient's clinical condition. Key considerations include:

• The use of novel β-lactam agents like ceftazidime/avibactam and meropenem/vaborbactam for CRE infections 1.
• The potential role of imipenem/relebactam and cefiderocol in certain cases 1, 2.
• The importance of combination therapy, such as ceftazidime/avibactam plus aztreonam, for MBL-producing CRE infections 2.
• The need for ongoing monitoring of resistance patterns and adaptation of treatment guidelines accordingly 1, 2.

From the FDA Drug Label

Table 16. Clinical Cure Rates at TOC by Baseline Pathogen from the Phase 3 cIAI Trial, mMITT Population Aerobic Gram-negative group or pathogen AVYCAZ plus metronidazolea n/N (%) Meropenemb n/N (%) ... Klebsiella pneumoniae 40/51 (78.4) 37/49 (75.5)

Table 19. Microbiological Cure Rate at TOC by Baseline Pathogen from cUTI Trial 1, mMITT Population Aerobic Gram-negative group or pathogen AVYCAZa n/N (%) Doripenemb n/N (%) ... Klebsiella pneumoniae 33/44 (75.0) 35/56 (62.5)

The antibiotics effective against Klebsiella pneumoniae are:

• AVYCAZ (ceftazidime and avibactam), with clinical cure rates of 78.4% in the cIAI trial and microbiological cure rates of 75.0% in the cUTI trial 3
• Meropenem, with clinical cure rates of 75.5% in the cIAI trial 3
• Doripenem, with microbiological cure rates of 62.5% in the cUTI trial 4

From the Research

Effective Antibiotics Against Klebsiella pneumoniae

The following antibiotics have been found to be effective against Klebsiella pneumoniae:

• Carbapenems, such as imipenem and meropenem, which are highly resistant to hydrolysis by TEM and SHV related beta-lactamases 5, 6
• High-dose amoxicillin with clavulanic acid, which has been shown to be effective in treating urinary tract infections caused by ESBL-producing K. pneumoniae 7
• Ceftazidime-avibactam, a combination of a cephalosporin and a beta-lactamase inhibitor, which has been found to be active against KPC-producing K. pneumoniae 8
• Polymyxins, such as colistin, which can be used in combination with carbapenem or other agents to treat infections caused by K. pneumoniae 9

Mechanisms of Resistance

Klebsiella pneumoniae can develop resistance to antibiotics through various mechanisms, including:

• Production of extended-spectrum beta-lactamases (ESBLs), which can hydrolyze and inactivate many beta-lactam antibiotics 5, 6
• Production of carbapenemases, which can hydrolyze and inactivate carbapenems 9
• Mutations in porin genes, such as ompK36, which can confer high-level carbapenem resistance 8

Treatment Considerations

When treating infections caused by K. pneumoniae, it is essential to consider the following:

• The use of carbapenems, such as imipenem and meropenem, as the primary treatment option 5, 6
• The potential for resistance to develop, and the need for judicious use of antibiotics to prevent the emergence of resistance 8
• The use of combination therapy, such as polymyxins with carbapenem or other agents, to treat infections caused by multidrug-resistant K. pneumoniae 9