From the Guidelines
Acinetobacter baumannii infections should be treated with combination therapy, including colistin and high-dose sulbactam, for patients with severe and high-risk infections, as recommended by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines 1. The treatment of Acinetobacter baumannii infections is challenging due to increasing carbapenem resistance, and combination therapy is often necessary for multidrug-resistant strains.
Key Considerations
- The ESCMID guidelines suggest using ampicillin-sulbactam for patients with CRAB susceptible to sulbactam and hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP) 1.
- For patients with CRAB resistant to sulbactam, a polymyxin or high-dose tigecycline can be used if active in vitro, but the guidelines do not recommend a preferred antibiotic due to lack of evidence 1.
- The guidelines conditionally recommend against using cefiderocol for the treatment of infections caused by CRAB 1.
- A network meta-analysis of 12 studies evaluating 8 antimicrobial treatments for CRAB infections found that combination therapy, including colistin and sulbactam, had a higher clinical cure rate than monotherapy 1.
Treatment Options
- Colistin (loading dose of 9 million units followed by 4.5 million units IV every 12 hours) plus high-dose sulbactam (6-9 g per day) is a recommended combination therapy for CRAB infections 1.
- Tigecycline monotherapy is not recommended due to a higher rate of treatment failure compared to colistin monotherapy, colistin combination therapy, and sulbactam-based therapy 1.
- Minocycline has in vitro activity against CRAB, but its use is not included in the meta-analysis due to limited evidence 1.
Clinical Considerations
- Susceptibility testing is crucial as resistance patterns vary widely, and source control through removal of infected devices or drainage of abscesses is essential when applicable.
- Treatment duration typically ranges from 7-14 days depending on infection site and severity.
- Clinicians should consider local antimicrobial susceptibility, patient renal and hepatic functions, and comorbidities when deciding on a treatment regimen.
From the FDA Drug Label
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 following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following bacteria exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for tigecycline against isolates of similar genus or organism group... Gram-negative bacteria Acinetobacter baumannii
Tigecycline may be used to treat Acinetobacter baumannii infections, although resistance has been reported and its clinical significance is unknown 2.
- In vitro data show that at least 90% of Acinetobacter baumannii exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for tigecycline.
- However, the efficacy of tigecycline in treating clinical infections caused by Acinetobacter baumannii has not been established in adequate and well-controlled clinical trials.
- Monitoring for relapse of infection is important, and more frequent monitoring is suggested if resistance is suspected.
From the Research
Indications for Treatment of Acinetobacter baumannii
- Acinetobacter baumannii is a major cause of healthcare-associated infections, including:
- Bacteremia
- Pneumonia/ventilator-associated pneumonia (VAP)
- Meningitis
- Urinary tract infection
- Central venous catheter-related infection
- Wound infection 3
- The optimal treatment for A. baumannii nosocomial infections has not been established, especially for multidrug-resistant (MDR) strains 3
Antibiotics Effective Against A. baumannii
- Carbapenems (imipenem, meropenem, doripenem) are the mainstay of treatment for A. baumannii 3
- Other effective antibiotics include:
- Polymyxins E and B
- Sulbactam
- Piperacillin/tazobactam
- Tigecycline
- Aminoglycosides 3
- Combination therapy with colistin and rifampicin has been shown to be effective and safe for severe infections due to MDR A. baumannii 4
Treatment of Colistin-Resistant A. baumannii
- Colistin-resistant A. baumannii is emerging, particularly in patients who have received colistin methansulfonate (CMS) for treatment of carbapenem-resistant, colistin-susceptible A. baumannii infection 5
- The treatment regimen for colistin-resistant A. baumannii infection associated with the lowest mortality rate was a combination of CMS, a carbapenem, and ampicillin-sulbactam 5
New Therapeutic Options
- New agents such as Cefiderocol, the combination of Sulbactam and Durlobactam, and the new Tetracyclines offer therapeutic options that need to be supported by clinical evidence 6
- Bacteriophage therapy is a promising alternative to antibiotic treatment for A. baumannii infections 6
Antimicrobial Susceptibility Testing
- The reliability of commonly used methods (disc diffusion, Etest and VITEK(®) 2) for testing sensitivity to tigecycline and colistin has been assessed, and proposed breakpoints have been established 7