Ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) in patients hospitalized in intensive care units (ICUs) is an important and challenging complication, including in patients with coronavirus disease 2019 (COVID-19). Considering the poor lung penetration of most antibiotics, including intravenous colistin due to the poor pharmacokinetics/pharmacodynamics at the infection site, the choice of the best antibiotic regimen is still being debated. This single-centre, observational study was conducted from March 2020 to August 2022, and included all patients hospitalized consecutively with VAP and concomitant bloodstream infection due to CRAB in the COVID-ICU. The main goal of the study was to evaluate risk factors associated with survival or death at 30 days from VAP onset. A propensity score for receiving therapy was added to the model. During the study period, 73 patients who developed VAP and concomitant positive blood cultures caused by CRAB were enrolled in the COVID-ICU. Of these patients, 67 (91.7%) developed septic shock, 42 (57.5%) had died at 14 days and 59 (80.8%) had died at 30 days. Overall, 54 (74%) patients were treated with a colistin-containing regimen and 19 (26%) were treated with a cefiderocol-containing regimen. Cox regression analysis showed that chronic obstructive pulmonary disease and age were independently associated with 30-day mortality. Conversely, cefiderocol-containing regimens and cefiderocol + fosfomycin in combination were independently associated with 30-day survival, as confirmed by propensity score analysis. This real-life study in patients with bacteraemic VAP caused by CRAB provides useful suggestions for clinicians, showing a possible benefit of cefiderocol and its association with fosfomycin.
1 August 2019 in Journal of Antimicrobial Chemotherapy
It is estimated that antimicrobial resistance (AMR) is responsible for nearly 5 million human deaths worldwide each year and will reach 10 million by 2050. Carbapenem-resistant Acinetobacter baumannii (CRAB) infections represent the fourth-leading cause of death attributable to antimicrobial resistance globally, but a standardized therapy is still lacking. Among the antibiotics under consideration, Sulbactam/durlobactam seems to be the best candidate to replace current back-bone agents. Cefiderocol could play a pivotal role within combination therapy regimens. Due to toxicity and the pharmacokinetics/pharmacodynamics (PK/PD) limitations, colistin (or polymyxin B) should be used as an alternative agent (when no other options are available). Tigecycline (or minocycline) and fosfomycin could represent suitable partners for both NBLs. Randomized clinical trials (RCTs) are needed to better evaluate the role of NBLs in CRAB infection treatment and to compare the efficacy of tigecycline and fosfomycin as partner antibiotics. Synergism should be tested between NBLs and “old” drugs (rifampicin and trimethoprim/sulfamethoxazole). Huge efforts should be made to accelerate pre-clinical and clinical studies on safer polymyxin candidates with improved lung activity, as well as on the iv rifabutin formulation. In this narrative review, we focused the antibiotic treatment of CRAB infections in view of newly developed β-lactam agents (NBLs).
Multiplex Polymerase Chain Reaction (PCR) has significantly impacted the field of infectious disease diagnostics, offering rapid and precise identification of bacterial and fungal pathogens. Unlike traditional culture methods, which may take days to yield results, multiplex PCR provides diagnostic insights within hours, enabling faster, targeted antimicrobial therapy and reducing the delay in treating critical infections like sepsis. The technique’s high sensitivity and broad pathogen coverage make it ideal for both single and polymicrobial infections, improving outcomes across respiratory, bloodstream, and bacterial/fungal infections. However, multiplex PCR is not without challenges; initial high costs and the need for specialized training can limit its adoption, especially in low-resource settings. This review discusses the clinical advantages and limitations of multiplex PCR, highlighting its influence on diagnostic accuracy, antimicrobial stewardship, and the global fight against antimicrobial resistance (AMR). Furthermore, recent innovations in multiplex PCR, such as digital PCR and portable devices, are explored as potential tools for expanding access to rapid diagnostics worldwide.
Carbapenem-resistant Acinetobacter baumannii (CRAB) is an emerging and important major cause of nosocomial infections, posing a significant challenge to clinicians worldwide. The intrinsic and acquired resistance mechanisms exhibited by CRAB, associated with its ability to persist in healthcare environments, have transformed it into a critical public health concern. The clinical implications of CRAB infections include severe manifestations, like ventilator-associated pneumonia and bloodstream infections. These infections are often associated with increased morbidity and mortality, particularly in critically ill patients, such as those in intensive care units, immunocompromised, and those undergoing invasive procedures. Considering these characteristics, the therapeutic armamentarium for the treatment of CRAB infections is increasingly limited, as these strains exhibit resistance to a broad range of antibiotics, including carbapenems and the new β-lactam inhibitors, which are considered last-line agents for many bacterial infections. An important role is represented by cefiderocol and data from real-world evidence. The aim of this narrative review is to discuss the main topics of CRAB infection and strategies for prevention, management, and therapy.
The COVID-19 pandemic may have had an effect on antimicrobial resistance. We compared the prevalence of ESKAPE multidrug-resistant (MDR) bacterial infections in COVID-19 affected/unaffected patients admitted to intensive care units (ICU) or infectious disease units at the “Mater Domini” University Hospital of Catanzaro between 1 March 2020 and 31 July 2021. Moreover, an analysis of MDR rates in ICU comparing the pre-pandemic period with the pandemic period was performed, and the possible consequence on in-hospital mortality was explored. One hundred and eighty-four ESKAPE isolates were analyzed from 362 SARS-CoV-2 positive and 199 negative patients. In total, 116 out of 171 Gram-negative isolates were classified as MDR, and a higher frequency was observed in COVID-19 compared with non-COVID-19 patients (74.2% vs. 60.3%; p = 0.052). A higher rate of MDR ESKAPE bacteria was observed in COVID-19 patients admitted to the ICU compared with COVID-19 unaffected patients admitted to the same ward in 2019 (88% vs. 80.4%; p = 0.186). Acinetobacter baumannii was the main pathogen in COVID-19 patients (58.7%), where it was the most frequent cause of bloodstream infection with the highest mortality rate (68.7%). Increase in MDR appeared to be associated with COVID-19 but only in the ICU setting. Acinetobacter baumannii was associated with the risk of death, indicating the importance of implementing infection control measures urgently.