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Variable outcomes have been reported with cefiderocol in infections due to carbapenem-resistant Acinetobacter baumannii (CRAB). Nonetheless, it may be the only option for metallo-beta-lactamase-producing strains. We describe an outbreak of NDM-CRAB infections treated with cefiderocol. Thirty-eight patients were colonized and/or infected. Thirteen patients developed a systemic infection. A clinical cure was achieved in 10 (83%) patients, one VAP and 9 BSIs, at day 7. In vitro, the activity of cefiderocol does not appear to match in vivo effectiveness using currently available commercial tests. Despite high clinical cures, overall mortality remains high in severely ill patients. Cefiderocol may be considered in this specific setting, though the implementation of susceptibility tests and infection control measures is mandatory. [ABSTRACT FROM AUTHOR]

Meningitis and ventriculitis, due to carbapenem-resistant Enterobacterales, are frequently associated with significant morbidity and mortality. In the case of multi-drug-resistant pathogens, it is necessary to consider the limited susceptibility profile as well as the penetration of the antimicrobials into the brain. Limited data are available regarding the treatment of central nervous system infections caused by carbapenem-resistant Enterobacterales. We report a study of a patient treated with meropenem–vaborbactam in the case of post-neurosurgical meningitis due to carbapenemase-producing Klebsiella pneumoniae (CPKP). [ABSTRACT FROM AUTHOR]

Antibiotic-associated diarrhea (AAD) is defined as an otherwise unexplained diarrhea that occurs in association with the administration of antibiotics. Its incidence varies among antibacterial agents from5 to 10 % with ampicillin, 10 to 25 % with amoxicillin--clavulanate, 15 to 20 % with cefixime, 2 to 5 % with other cephalosporins, fluoroquinolones, azithromycin, clarithromycin, erythromycin and tetracycline. Clostridium difficile associated-diarrhea (CDAD) is a severe side effect of antibiotic therapy, with epidemics documented in U.S.A., Europe and Canada. Recurrent Clostridium associated-diarrhea occurs in 10-20% of al CDAD and can be difficult to treat, but there is evidence for probiotics usefulness as a component of therapeutic strategy. The most studied probiotics include Saccharomyces boulardi and Lactobacillus spp. Antibiotics have multiple effects on the pathogenesis of AAD including some that are independent from their antimicrobial activity. Specifically, erythromycin acts as an agonist of the motilin receptor accelerating the rate of gastroenteric motility; clavulanate in amoxicillin-clavulanate appears to stimulate small-bowel motility and penicillins may rarely cause segmental colitis. Furthermore antibiotics may substantially reduce the concentration of fecal anaerobes and as a consequence the metabolism of carbohydrates may decrease leading to osmotic diarrhea. Probiotics promote an increasing of free acids in the gut lowering luminal pH, which suppresses the growth of pathogenic flora. Probiotics also decrease the colonization of pathogenic organisms in the gut by secreting hydrogen peroxide and organic acids that are locally toxic to pathogenic bacteria and may competitively block microbial adhesion to the gut epithelium. Moreover, certain probiotic strains may have immunomodulating effects such as increase cytokme activity and stimulate lymphocyte and macrophage phagocytosis in the intestine. Five meta-analyses on probiotics usefulness for the prevention of AAD have been performed. The largest meta-analysis to date analyzes 25 randomized controlled trials on probiotics including 2810 subjects has showed an overall reduction in the risk of AAD when probiotics were co-administered with antibiotics. Probiotics are generally safe but should be used with caution in categories of patients with deficiency of the immune system or with disruption of the integrity of the intestinal mucosa. Caution should be warranted also in presence of a central venous catheter, since some systemic infections sustained by probiotics have been reported in this setting. In spite of some evidence consensus statements favoring the use of probiotics in the prevention of AAD is lacking, due to the difficulties in analyzing the available studies. The differences of sample sizes with heterogeneous populations, the differences in the given dose of probiotics agents, the differences in the amounts of viable organisms administered represent the main factors impacting the correct interpretation of the promising results found in these studies. Moreover, study designs are not homogeneous as well as endpoints and objectives that do not include assessments of possible adverse events. In conclusion, albeit some promising results on the efficacy of probiotics in the prevention of AAD and C. difficile associated diarrhea, there are no evidence-based guidelines regarding probiotics for this use. Adequately powered, double blind randomized controlled trials are needed to assess the efficacy of specific probiotic strains. [ABSTRACT FROM AUTHOR]

Background. Epstein-Barr virus (EBV) is pathogenically linked to human immunodeficiency virus (HIV)- related primary central nervous system lymphoma (PCNSL) and is found in virtually all HIV-related PCNSL cases. The objective of this study was to assess the effect of ganciclovir on EBV DNA replication in patients with HIV- related PCNSL. Patients and methods. EBV DNA was measured by real-time polymerase chain reaction in cerebrospinal fluid and plasma samples from 25 patients with HIV-related PCNSL. Eight of these patients were receiving ganciclovir for concurrent cytomegalovirus infections. Results. EBV DNA was detected in cerebrospinal fluid samples obtained from 15 (88%) of 17 ganciclovir-untreated patients and 4 (50%) of 8 ganciclovir-treated patients (P = .028). EBV DNA load was significantly lower for treated patients, compared with untreated patients (median value, 2.15 vs. 4.16 log copies/mL; P = .001). Analysis of sequential cerebrospinal fluid samples from 7 patients showed that EBV DNA decreased in samples obtained from 2 patients following the start of ganciclovir administration but did not decrease in samples obtained from the 5 untreated patients. In addition, patients who received ganciclovir survived longer than the untreated patients (median duration of survival, 181 vs. 72 days; P = .006). Conclusion. The effect of ganciclovir on EBV DNA load in cerebrospinal fluid supports the hypothesis that EBV is replicating in patients with PCNSL. This observation, together with the effect of ganciclovir therapy on patient survival, suggests that this drug might be useful for the management of PCNSL. [ABSTRACT FROM AUTHOR]