What is the treatment for Carbapenem-resistant Acinetobacter baumannii (CR-Ab) infection?

From the Guidelines

Colistin monotherapy is the recommended treatment for Carbapenem-resistant Acinetobacter baumannii (CR-Ab) infection, as combination therapy with carbapenems has not shown significant benefits in clinical studies. The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines suggest that combination therapy for CRAB has been proposed based on in vitro studies, but clinical adoption requires assessment in clinical studies 1. Recent clinical trials, such as the AIDA RCT and the OVERCOME trial, have shown no significant difference between colistin monotherapy and colistin-meropenem combination therapy in terms of clinical failure or mortality 1.

Some key points to consider when treating CRAB infections include:

• Colistin is the backbone of treatment, with a recommended loading dose of 9 million units followed by 4.5 million units every 12 hours 1
• Combination therapy with carbapenems, such as meropenem, may not be beneficial and should be avoided unless the isolate has a lower MIC to the carbapenem 1
• Treatment duration typically ranges from 7-14 days, depending on the infection site and clinical response
• Source control through drainage of abscesses or removal of infected devices is crucial
• Dosing adjustments are required for patients with renal impairment, particularly for colistin and polymyxins, which can cause nephrotoxicity

It is essential to note that the evidence for combination therapy is mostly based on low-certainty observational studies, and high-certainty evidence from RCTs suggests that combination therapy may not be beneficial 1. Therefore, colistin monotherapy remains the recommended treatment for CRAB infections, unless specific circumstances, such as lower MICs to carbapenems, are present.

From the FDA Drug Label

Tigecycline has been shown to be active against most of the following microorganisms, both in vitro and in clinical infections... Gram-negative bacteria... Acinetobacter baumannii*

*There have been reports of the development of tigecycline resistance in Acinetobacter infections seen during the course of standard treatment. Such resistance appears to be attributable to an MDR efflux pump mechanism

The treatment for Carbapenem-resistant Acinetobacter baumannii (CR-Ab) infection is tigecycline (IV), however, it is essential to note that resistance to tigecycline has been reported in Acinetobacter infections, and monitoring for relapse is crucial. Key points to consider:

• Tigecycline resistance: may develop during standard treatment
• MDR efflux pump mechanism: a possible cause of resistance
• Monitoring: frequent monitoring for relapse is suggested, with blood and specimen cultures to identify and test bacterial isolates for susceptibility to tigecycline and other antimicrobials 2

From the Research

Treatment Options for Carbapenem-resistant Acinetobacter baumannii (CR-Ab) Infection

The treatment of CR-Ab infections is challenging due to limited treatment options and high resistance rates to multiple antibiotics. Current treatment plans include:

• High-dose ampicillin-sulbactam, often combined with high-dose tigecycline, as recommended by the Infectious Diseases Society of America (IDSA) 3
• Colistin, which is considered a primary treatment, often used in combination with other antimicrobials such as tigecycline, ampicillin-sulbactam, meropenem, or fosfomycin 3, 4
• Combination therapy with colistin and sulbactam, which has shown synergistic activity against CR-Ab isolates 5
• Triple combination therapy with high-dose ampicillin/sulbactam, high-dose tigecycline, and colistin, which has been used to treat ventilator-associated pneumonia caused by pan-drug resistant Acinetobacter baumannii 6

Antimicrobial Combinations and Synergistic Activities

Studies have investigated the synergistic activities of various antimicrobial combinations against CR-Ab, including:

• Colistin and sulbactam, which showed enhanced bacterial killing in static and dynamic time-kill studies 5
• Imipenem and colistin, which demonstrated synergy in checkerboard titration and time-kill assays 4
• Tigecycline and colistin, which showed good in vitro synergy for CR-Ab with high imipenem resistance 4

Clinical Outcomes and Mortality Rates

Clinical outcomes and mortality rates for patients treated with different antimicrobial regimens for CR-Ab infections have been reported, including:

• A case series study that found a high clinical cure rate (90%) and low mortality rate (10%) in patients treated with triple combination therapy 6
• An observational cohort study that found no association between combined targeted therapy with colistin and tigecycline and lower 30-day crude mortality rates 7