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Introduction: Real-life experience with imipenem/cilastatin/relebactam (IMI/REL) for the treatment of KPC-producing Klebsiella pneumoniae complex (KPC-Kp) and difficult-to-treat resistance (DTR) Pseudomonas aeruginosa (DTR-PA) infections is herein described., Methods: Adult patients with KPC-Kp or DTR-PA infections who received ≥48 h of IMI/REL were included. Clinical and microbiological outcomes were retrieved through the medical records. Primary outcome was clinical cure. Secondary outcomes included mortality from infection onset and adverse effects attributable to IMI/REL., Results: We included 10 patients with different infections caused by DTR-PA ( n  = 4), KPC-Kp [ n  = 5, of which 3 ceftazidime/avibactam-resistant (CTV-R KPC-Kp), 2 CTV susceptible (CTV-S KPC-Kp)] or both DTR-PA/KPC-Kp ( n  = 1) successfully treated with IMI/REL: 3 hospital-acquired pneumonia, 1 ventilator-associated pneumonia, 2 skin and soft tissue infections, 1 osteomyelitis, 2 bloodstream infections, 1 complicated urinary tract infection. Clinical cure was achieved in all cases. No patients died and no side effect were reported., Discussion: We reported the preliminary real-life experience on the successful and safe use of IMI/REL for the treatment of KPC-Kp or DTR-PA complicated infections, including pneumonia and bone infections., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Leanza, Mascellino, Volpicelli, Covino, Falletta, Cancelli, Franchi, Carnevalini, Mastroianni and Oliva.)

Brucellosis is a highly contagious zoonotic disease and a major human health problem worldwide. Due to its ways of transmission, direct or indirect contact with infected animals or their contaminated biological products, the disease exhibits strong occupational association with animal handlers comprising a significant population at risk. This study was undertaken to estimate the seroprevalence of brucellosis in animal handlers and to understand the epidemiological and serological aspects of the same. The animal handlers from the state of West Bengal, India were included in this study. It was a prospective and observational cohort study from November 2021 to March 2022. A total of 669 sera samples were collected from animal handlers and tested using various serological tests for Brucella antibodies. All serum samples were tested using the Rose Bengal plate test (RBPT), standard tube agglutination test (STAT), and enzyme-linked immunosorbent assay (ELISA). 106 (15.8%) patients were diagnosed with brucellosis among the total number of patients tested. Most of the patients affected with brucellosis belonged to the age group 51-60 years (23.5%). The seropositivity rate in male animal handlers was higher than female animal handlers in this study. More studies are needed to understand the occupational association of this disease. Awareness programs, safe livestock practices, and prevention of the disease by timely diagnosis must be implemented in order to control human brucellosis., Competing Interests: Conflicts of interest: Maria Teresa Mascellino is an editorial board member for AIMS Microbiology and was not involved in the editorial review or the decision to publish this article. All authors declare that there are no competing interests., (© 2024 the Author(s), licensee AIMS Press.)

Objectives: Little is known regarding outcomes and optimal therapeutic regimens of infections caused by Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) resistant to ceftazidime/avibactam (CZA) and susceptible to meropenem (MEM). Although susceptible to MEM in vitro, the possibility of developing MEM resistance overtime is a concern. We describe the clinical characteristics of patients with colonization/infection due to KPC variants with a focus on the in vitro activity of fosfomycin (FOS)-containing combinations., Methods: Patients with colonization/infection due to a KPC variant were included. Fosfomycin susceptibility was performed by agar dilution method. Synergistic activity of FOS-based combinations was evaluated by gradient strip-agar diffusion method. The emergence of in vitro MEM resistance was also tested., Results: Eleven patients were included: eight with infection [four with ventilator-associated pneumonia and four with bloodstream infections] and three with colonization. Previous therapy with CZA was administered to all patients (with a mean cumulative duration of 23 days). All subjects with infection received meropenem, in monotherapy (n = 4) or with amikacin (n = 2) or fosfomycin (n = 2), and achieved clinical cure. A new CZA-susceptible and MEM-resistant KPC-Kp strain was subsequently isolated in three patients (27.3%). Meropenem/vaborbactam (MVB) showed high in vitro activity, while FOS+MEM combination was synergistic in 40% of cases. In vitro resistance to MEM was observed with maintenance of CZA resistance., Conclusions: Detection of KPC variants may occur within the same patient, especially if CZA has been previously administered. Although clinical success has been obtained with carbapenems, the emergence of MEM resistance is a concern. Fosfomycin plus meropenem is synergistic and may be a valuable combination option for KPC variants, while MVB may be considered in monotherapy. The detection of KPC variants in an endemic setting for KPC-Kp represents a worryingly emerging condition. The optimal therapeutic approach is still unknown and the development of meropenem resistance is of concern, which may lead to therapeutic failure in clinical practice. In these cases, the addition of fosfomycin to meropenem, or a more potent antibiotic, such as meropenem/vaborbactam, may be valuable therapeutic options., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Nosocomial infections by multidrug-resistant (MDR) bacteria are among the main causes of morbidity and death in patients hospitalized in intensive care units (ICUs) worldwide. Antibiotic resistance has become a major concern for treating the patients with nosocomial infections. The aim of this study was to describe the antibiotic resistance patterns of pathogens causing infections in adult and pediatric patients in the ICUs of a tertiary care hospital in Kolkata, India. A cross-sectional, retrospective study was conducted from January 2022 to October 2022 on a total of 139 adult and 146 pediatric patients. Depending on clinical symptoms of the patients, samples were collected and subjected to antibiotic sensitivity testing. The culture and sensitivity pattern of clinical isolates from blood, urine, sputum, endotracheal tube (ET) aspirate, and central line catheter insertion site swabs were analyzed. A total of 695 and 556 specimens were obtained from adult and pediatric ICU, respectively. Culture positivity rate among adults and pediatric patients were 37% and 40%, respectively. The most commonly isolated organisms were Gram-negative Enterobacterales and non-fermenters. Most of the bacterial isolates showed very high resistance against multiple antibiotics. Escherichia coli from adult and pediatricpatients were found to be resistant to second generation cephalosporins (95% and 96%, respectively), beta-lactams (95% and 63%, respectively), fluoroquinolones (95% and 81%, respectively), and cotrimoxazole (85% and 78%, respectively). Klebsiella spp. from adult patients were found to be resistant to aminoglycosides (75%), second generation cephalosporins (100%), beta-lactams (94%), fluoroquinolones (92%), carbapenems (88%), and cotrimoxazole (83%). Proteus spp., Acinetobacter baumannii , and Pseudomonas spp. werefound to be resistant to multiple antibiotics. Enterococcus spp. from ICUs showed more than 90% resistance against ampicillin and more than 75% resistance against fluoroquinolones. MDR bacterial infections are increasing in both adult and pediatric ICUs, leading to significant therapeutic challenges. A frequent study of antimicrobial resistance patterns is imperative for antibiotic stewardshipin combatting the deadly effect of the MDR bacteria in critically ill patients.

Enteric fever, a potentially fatal multisystem disease that is caused by Salmonella enterica serovar Typhi and Paratyphi, poses a significant risk in low- and middle-income countries. A retrospective study to understand the prevalence and evolving patterns of antibiotic resistance in Salmonella Typhi and Paratyphi was undertaken from June 2017 to June 2022. A total of 4051 blood samples were collected from patients attending inpatient and outpatient departments of the School of Tropical Medicine (Kolkata, India) hospital. Blood samples were cultured, and culture positive samples were further processed for identification using conventional and automated systems. Antibiotic susceptibility test was performed using both the Kirby-Bauer disc diffusion method and VITEK2 (bioMerieux). Forty-five (1.1%) Salmonella species were isolated among the number of total ( n = 4051) samples that were tested. Out of the 45 Salmonella isolates, 35 were Salmonella Typhi (77.77%) and 10 were Salmonella Paratyphi A (22.23%). We found pronounced fluoroquinolone resistance of 100% in the recent years (2019-2022) in both of the S . Typhi and S . Paratyphi A isolates. We found that 1 Salmonella Typhi and 2 Salmonella Paratyphi A isolates were resistant against multiple antibiotics (cefixime, ceftriaxone, ciprofloxacin and nalidixic acid), and 1 multidrug-resistant (MDR) Salmonella Paratyphi A isolate was found in a recent study year (2020) and it showed resistance against different classes of antibiotics (cephalosporins, fluoroquinolones and carbapenems). There was no resistance that was detected to the 3 rd generation cephalosporins in the final years of the study. The emergence of Salmonella isolates that are resistant to multiple antibiotics poses a serious health problem. The antimicrobial resistance patterns that were detected in the study thus warrant further studies to understand the antibiotic susceptibility and resistance pattern of Salmonella against the major classes of antibiotics., Competing Interests: The authors declare no conflict of interest.

Aim: The aim of the study was to evaluate the in vitro activity of N-acetylcysteine (NAC), alone or in combination with beta-lactams, against carbapenem-resistant Klebsiella pneumoniae (CR-Kp) and Acinetobacter baumannii (CR-Ab)., Methods: The antibacterial activity of each compound was tested by broth microdilution and the synergism was evaluated by the checkerboard method. Killing studies of NAC alone and in combination with beta-lactams were performed. Bacterial morphological changes were investigated with scanning electron microscopy (SEM)., Results: Overall, 30 strains were included (15 CR-Kp and 15 CR-Ab). The NAC Minimal Inhibitory Concentrations (MIC)50/90 were 5/5 and 2.5/5 mg/mL for CR-Kp and CR-Ab, respectively. For both microorganisms, NAC, in addition to beta-lactams (meropenem for CR-Kp, meropenem and ampicillin/sulbactam for CR-Ab, respectively), was able to enhance their activity. The killing studies showed a rapid and concentration-dependent activity of NAC alone; the addition of NAC to meropenem or ampicillin/sulbactam at subinhibitory concentrations induced a fast and lasting bactericidal activity that persisted over time. The SEM analyses showed evident morphological alterations of the bacterial cells following incubation with NAC, alone and in combination with meropenem., Conclusions: NAC demonstrated a high in vitro activity against CR-Kp and CR-Ab and was able to enhance beta-lactams' susceptibility in the tested strains. The preliminary data on the SEM analyses confirmed the in vitro results.