Editor’s Note:

Carbapenem-resistant Acinetobacter baumannii (CRAB) infection is considered one of the most challenging issues among carbapenem-resistant gram-negative bacteria (CRO) due to limited effective treatment options. Colistin, a polymyxin antibiotic used for “repurposing” in the treatment of CRAB, is one of the few choices available in China. A recent presentation at the 2023 IDWeek congress reported findings from a single-center cohort study conducted in South Korea, suggesting that colistin therapy for CRAB pneumonia lacks efficacy and is associated with an increased incidence of acute kidney injury (AKI) [1]. Dr. Yi Shi from Jinling Hospital, Nanjing University School of Medicine, provides an introduction and commentary on this study below.

 

Research Introduction

 

Acinetobacter baumannii is a major pathogen in nosocomial infections, and its resistance to carbapenems limits suitable antibiotic choices. Colistin has been used to treat carbapenem-resistant A. baumannii (CRAB), but only a few studies have assessed colistin’s effectiveness with appropriate controls. This study aimed to evaluate the efficacy of colistin compared to other non-active drugs in treating CRAB.

This study screened adult patients (≥18 years) with CRAB isolated from respiratory specimens, and those were treated either with colistin monotherapy (colistin group) or without any active antimicrobial drugs (non-active drug group) based on susceptibility testing. Pneumonia was defined as the appearance of new infiltrative lesions on chest imaging along with two of the following: 1) fever or hypothermia (≥37.8℃ or ≤36.0℃), 2) purulent respiratory secretions, 3) increased white blood cell count, 4) hypoxemia. The primary outcome was the 30-day all-cause mortality rate. Secondary outcomes included AKI within 30 days after pneumonia diagnosis or colistin administration, evaluated only in patients with baseline creatinine below 2mg/dL.

Among 828 patients with CRAB infection identified from respiratory specimens, 45 patients received colistin treatment, and 123 did not receive any active antimicrobial drugs against CRAB. The majority of CRAB pneumonia (91.1%) was hospital-acquired pneumonia (HAP), with 51.1% being ventilator-associated pneumonia (VAP). The colistin group showed significantly higher rates of purulent respiratory secretions (100% vs. 87.8%, P=0.012) and use of carbapenems (71.1% vs. 48.8%, P=0.010) compared to the non-active drug group.

 

The 28-day all-cause mortality rates were 41.7% in the colistin group and 43.9% in the non-active drug group, with no significant difference (adjusted HR 0.74, P=0.201). The colistin group had a higher incidence of AKI (61.0% vs. 34.7%), but the difference was not statistically significant (P=0.143). Univariate or multivariate analysis indicated that the SOFA score was a predictive factor for AKI.

Dr. Yi Shi’s Comment

The World Health Organization (WHO) categorizes gram-negative bacteria such as CRAB, carbapenem-resistant Pseudomonas aeruginosa (CRPA), and carbapenem-resistant Enterobacteriaceae (CRE) as “Critical,” requiring the development of new antimicrobial drugs. Bacterial resistance has become a global public health threat, particularly with CRO infections facing a “no drugs available” dilemma in many regions.

Currently, the arsenal for treating CRO in China is quite limited, primarily consisting of the “three musketeers”: the combination of ceftazidime-avibactam, the novel tetracycline drug tigecycline, and the “repurposed” polymyxin antibiotics. While Western countries offer a variety of novel ceftazidime-avibactam formulations, China has only ceftazidime-avibactam, which is inherently resistant to common CRAB phenotypes. Therefore, tigecycline and polymyxins, including colistin, are the available options for CRAB treatment in China. Although ceftazidime-avibactam formulations are recommended as the first choice according to guidelines from IDSA, ESCMID, among others, colistin or tigecycline-based combination therapy is suggested if efficacy is inadequate or inaccessible [2-3].

Colistin is the most widely used polymyxin antibiotic both domestically and internationally. According to the International Consensus Guidelines on Rational Use of Polymyxins, colistin, in combination with other sensitive drugs, is recommended for treating invasive CRAB infections based on MIC values. However, when there is no second MIC-sensitive drug available, colistin monotherapy is recommended [4]. Therefore, the question of whether colistin monotherapy is more effective than other non-active drugs against CRAB has been a long-standing concern. The retrospective study from South Korea provides some reference data.

This study retrospectively analyzed HAP patients with CRAB infection, including 45 cases treated with colistin and 123 cases treated with non-active drugs. The researchers clearly defined pneumonia to exclude CRAB carriers. Looking at the primary endpoint, there was no significant difference in the 28-day mortality rate between the two groups. However, the colistin group had an almost 25% increase in the incidence of AKI compared to the non-active group, although the difference was not statistically significant.

Last year, the Italian “Guidelines for the Diagnosis and Management of Multidrug-Resistant Organism Infections” stated that there is still a lack of convincing data on CRAB antibiotic treatment, and colistin therapy poses a higher risk of nephrotoxicity, necessitating strict monitoring of kidney function. The guidelines also highlighted ceftiderol as a promising new cephalosporin antibiotic for CRAB, requiring further in-depth research, including monotherapy or combination therapy [5]. This Korean retrospective study also suggests that colistin therapy for CRAB infection lacks efficacy and increases the risk of nephrotoxicity. Therefore, there is a need for the development and introduction of more new drugs for treating CRAB in the future.

Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University School of Medicine