Epidemiology and Prevention of Early Infections by Multi-Drug-Resistant Organisms in Adults Undergoing Liver Transplant: A Narrative Review.

Invasive bacterial infections are a leading cause of morbidity and mortality after liver transplant (LT), especially during the first months after LT, and infections due to multi-drug-resistant organisms (MDRO) are increasing in this setting. Most of the infections in patients in intensive care unit arise from the endogenous microflora and, for this reason, pre-LT MDRO rectal colonization is a risk factor for developing MDRO infections in the post-LT. Moreover, the transplanted liver may carry an increased risk of MDRO infections due to organ transportation and preservation, to donor intensive care unit stay and previous antibiotic exposure. To date, little evidence is available about how MDRO pre-LT colonization in donors and recipients should address LT preventive and antibiotic prophylactic strategies, in order to reduce MDRO infections in the post-LT period. The present review provided an extensive overview of the recent literature on these topics, with the aim to offer a comprehensive insight about the epidemiology of MDRO colonization and infections in adult LT recipients, donor-derived MDRO infections, possible surveillance, and prophylactic strategies to reduce post-LT MDRO infections.

Feasibility of Using Ceftazidime-Avibactam as a Therapeutic Option for Bloodstream Infections Caused by Multidrug-Resistant Enterobacterales and Pseudomonas aeruginosa Based on Its Susceptibility Profile.

Background In the era of increased antimicrobial resistance, there are limited therapeutic options available for the treatment of bacteremia caused by multidrug-resistant organisms (MDROs). This study aims to find out the feasibility of using ceftazidime/avibactam (CZA) as a therapeutic option for bloodstream infections caused by multidrug-resistant (MDR) Enterobacterales and Pseudomonas aeruginosa based on its susceptibility profile. Materials and methods The isolates were routinely subjected to antimicrobial susceptibility testing (AST) by an automated AST system (VITEK-2). Those isolates found as MDR (resistant to at least one drug for ≥3 antimicrobial classes) were tested against CZA by Kirby-Bauer's disk diffusion (kb-DD) method. Results A total number of 293 MDR Enterobacterales and 31 MDR P. aeruginosa isolates were included. Of these, 87.3% of isolates were found as carbapenem-resistant (CR), whereas 12.7% of isolates were found as carbapenem susceptible. About 30.6% of MDROs were susceptible to CZA. Among carbapenem-resistant organisms (CROs), CR Klebsiella pneumoniae(33.5%) is most susceptible to CZA, compared to CR P. aeruginosa(0%)and CREscherichia coli(3.2%). Among the MDR isolates that were susceptible to CZA (30.6%), the majority had poor susceptibility against other ß-lactam-ß-lactamase inhibitor (BL-BLI) agents. Among all antimicrobial agents tested against CROs, colistin (96%) was found to have the best susceptibility profile. Conclusion It is observed that CZA is an acceptable therapeutic option for the treatment of bacteremia caused by MDROs, especially CROs. Therefore, it is important for the laboratories to perform the AST for CZA if the healthcare settings intend to use CZA for the management of such "difficult-to-treat" bloodstream infections.

Opportunities and Challenges in Development of Live Biotherapeutic Products to Fight Infections.

Treatment of bacterial infections with broad-spectrum antibiotics is a strategy severely limited by the decreased ability of the perturbed resident microbiota to control expansion of antibiotic-resistant pathogens. Live biotherapeutic products (LBPs) could provide an alternative to antibiotics in infection control by restoring gut colonization resistance and controlling expansion of resistant strains, an important therapeutic need not being addressed with existing anti-infective drug modalities. We review opportunities and challenges in developing LBPs for multidrug-resistant organisms colonization and infection control, with a focus on commercial fecal microbiota transplantation-like products and defined bacterial consortia, and spanning considerations related to availability of models for rational drug candidate selection and dose regimen selection, good manufacturing practice, intellectual property, and commercial viability.

Chlorhexidine gluconate bathing in children with cancer or those undergoing hematopoietic stem cell transplantation: A double-blinded randomized controlled trial from the Children's Oncology Group.

BACKGROUND: To the authors' knowledge, information regarding whether daily bathing with chlorhexidine gluconate (CHG) reduces central line-associated bloodstream infection (CLABSI) in pediatric oncology patients and those undergoing hematopoietic stem cell transplantation (HCT) is limited. METHODS: In the current multicenter, randomized, double-blind, placebo-controlled trial, patients aged ≥2 months and <22 years with cancer or those undergoing allogeneic HCT were randomized 1:1 to once-daily bathing with 2% CHG-impregnated cloths or control cloths for 90 days. The primary outcome was CLABSI. Secondary endpoints included total positive blood cultures, acquisition of resistant organisms, and acquisition of cutaneous staphylococcal isolates with an elevated CHG mean inhibitory concentration. RESULTS: The study was stopped early because of poor accrual. Among the 177 enrolled patients, 174 were considered as evaluable (88 were randomized to the CHG group and 86 were randomized to the control group). The rate of CLABSI per 1000 central line days in the CHG group was 5.44 versus 3.10 in the control group (risk difference, 2.37; 95% confidence interval, 0.05-4.69 [P = .049]). Post hoc conditional power analysis demonstrated a 0.2% chance that the results would have favored CHG had the study fully enrolled. The rate of total positive blood cultures did not differ between groups (risk difference, 2.37; 95% confidence interval, -0.41 to 5.14 [P = .078]). The number of patients demonstrating the new acquisition of resistant organisms did not differ between groups (P = .54). Patients in the CHG group were found to be more likely to acquire cutaneous staphylococcal isolates with an elevated CHG mean inhibitory concentration (P = .032). CONCLUSIONS: The data from the current study do not support the use of routine CHG bathing in children with cancer or those undergoing allogeneic HCT.

Source, pattern and antibiotic resistance of blood stream infections in hematopoietic stem cell transplant recipients.

UNLABELLED: Mucositis developing as a result of myelo-ablative high dose therapy administered prior to hematopoietic stem cell transplantation (HSCT) is associated with the risk of bacteremia. The aim of the present study was to detect the pattern of bacteremia coinciding with the present practice of HSCT, to study the contribution of health-care associated infection (HAI) to the pattern of infection, in the context of the problem of antibiotic resistance in HSCT recipients. PATIENTS AND METHODS: This is a retrospective, single center study including patients who developed febrile neutropenia (FN) among HSCT recipients in one year duration. RESULTS: Ninety FN episodes were recorded in 50 patients. Out of 39 positive blood cultures, Gram negative rods (GNR) were the predominant pathogens, constituting 67% (n=26) of isolated organisms, while 33% of infections were caused by gram positive cocci (GPC) (n=13). Bacteremia was significantly associated with central venous line (CVL) infections and gastroenteritis (diarrhea and vomiting) with a p-value 0.024, 0.20 and 0.0001, respectively. Multi-drug resistant organisms (MDROs) were identified in 27 (69%) of the 39 positive blood cultures. CONCLUSION: In one year duration, gram negative pathogens were the predominant causes of infection in HSCT recipients with high rates of MDROs in our institution. Gastroenteritis and central venous line infections are the main sources of bacteremia.