Carbapenem-resistant Acinetobacter baumannii: in pursuit of an effective treatment

Abstract

Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) has gained global notoriety as a critically important nosocomial pathogen. It mostly affects debilitated patients, causing pneumonia and bloodstream infections with high mortality rates. Difficulties in treating CRAB infections stem from a formidable resistance profile that leaves available only a few antibiotics of uncertain efficacy such as colistin and tigecycline. Despite the relentless attempts to improve therapeutic approaches (as depicted in colistin-oriented randomized clinical trials and the numerous observational studies), progress is still limited. Aims: We aim (a) to assist physicians to adapt therapeutic approaches in CRAB infections by considering all potentially available antimicrobials, and (b) to present directions for future investigations that emerge through treatment efforts in endemic settings. Sources: Articles and reviews from PubMed and Scopus databases; studies from ClinicalTrials.gov; presentations from ECCMID congresses and IDWeek meetings. Content: The review provides a succinct overview of the important pharmacokinetic/pharmocodynamic parameters of relevant antimicrobial agents, a critical appraisal of randomized control trials and observational studies, suggestions for increasing the strength of observational studies and directions facilitating the choice of therapeutic regimens by severity of infection and status of the host. Implications: The lack of an optimal therapeutic regimen for CRAB thus far, as shown in this review, suggests the need to thoroughly investigate alternative approaches through carefully designed trials that should include all relevant drugs. Some of these alternative directions are indicated in the present review. E.-T.

In vitro synergistic activity of the sulbactam/avibactam combination against extensively drug-resistant Acinetobacter baumannii

“…ABA is often resistant to all β-lactam antibiotics and shows co-resistance to the majority of other antimicrobial agents, leaving very few treatment options available [1–5]. SUL in ABA inhibits PBP3, triggering metabolic perturbations [17]; however, SUL activity is limited by the action of β-lactamases.…”

“…Other antimicrobials with in vitro activity against ABA are minocycline, tigecycline and amikacin. None of the recently released combinations of β-lactams and β-lactamase inhibitors [ceftolozane-tazobactam, ceftazidime-avibactam (CAZ/AVI), meropenem-varbobactam] have been shown to be clinically useful against ABA infections [3–5]. Sulbactam (SUL) is a β-lactamase inhibitor with intrinsic activity against ABA [6].…”

Carbapenem-Resistant Gram-Negative Bacterial Infections in Children

“…Higher doses have been suggested in the adult population, taking into account a PK/pharmacodynamic benefit (147). Other alternatives are polymyxins, aminoglycosides, and tigecycline (148). Additionally, co-trimoxazole may be an optimal option for UTIs.…”

“…Generally, for severe infections or immunosuppressed patients, combination therapy should be considered. Cefiderocol is being used on a compassionate-use basis to treat infections caused by pan-drug-resistant isolates against which other options do not exist (148).…”

Bloodstream infections caused by ST2 Acinetobacter baumannii over 6 years in China: risk factors, antibiotic regimens and virulence

“…Meanwhile, tigecycline attains poor serum levels and has a limited record of treating serious infections [6]. While colistin and tigecycline are considered rst-line therapeutics for MDR-AB, there is still no optimal treatment plan for MDR-AB thus far [7].…”