Explore the vast range of titles available.

The possible negative impact of severe adult respiratory distress caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (COVID-19) on antimicrobial stewardship and infection control has been postulated, but few real-life data are available. The aim of this study was to report our experience with colonization/infection of carbapenem-resistant Pseudomonas aeruginosa (CRPA), carbapenem-resistant Klebsiella pneumoniae (CR-Kp) and Candida auris among critically ill COVID-19 patients admitted to the intensive care unit (ICU). All COVID-19 patients admitted to the ICUs at San Martino Policlinico Hospital–IRCCS in Genoa, Italy, were screened from 28 February to 31 May 2020. One-hundred and eighteen patients admitted to COVID-19 ICUs were included in the study. Among them, 12 (10.2%) became colonized/infected with CRPA, 6 (5.1%) with C. auris and 2 (1.6%) with CR-Kp. All patients with CRPA received prior treatment with meropenem, and in 11 (91.7%) infection was not preceded by colonization. Four patients (66.7%) developed C. auris candidemia. A significant spread of resistant pathogens was observed among critically ill COVID-19 patients. Dedicated strategies are warranted to prevent horizontal spread and maintain effective antimicrobial stewardship programs in the setting of COVID-19 care.

Background Human papillomavirus (HPV) adversely affects human reproduction. We aimed to evaluate the prevalence of HPV infection in men and its correlation with semen parameters and reproductive outcomes. Methods In this prospective observational cohort study, 384 semen samples were collected from 237 male partners of infertile couples. The presence of HPV DNA and genotyping were analyzed in semen by quantitative PCR. A total of 186 intrauterine inseminations (IUI) in 101 couples and 186 assisted reproduction techniques (ART) cycles in 155 couples were performed. Associations between HPV positivity and semen parameters and fertility outcomes were evaluated using a generalized linear mixed model. Results The prevalence of HPV was 22.7%. Twenty-three HPV types were detected and 69.5% of positive samples presented at least one high risk (HR)-HPV genotype. HPV-18 (14%), HPV-53 (10%), and HPV-56 (10%) were the most prevalent HR-HPV genotypes followed by HPV-16, HPV-31, and HPV-51 (8%). HPV-42 was the most prevalent low risk (LR)-HPV genotype (25%). More than one HPV type was detected in 41% of HPV + samples. After capacitation, 30% of HPV + samples remained positive. We found no relationship between HPV infection and sperm volume, sperm concentration, and progressive motility both before and after semen capacitation. We observed a not significant different clinical pregnancy per cycle in the HPV − (6.8%) and HPV + (5.0%) IUI. We did not find any significant difference in fertilization, cleavage, quality of developed embryos, blastocyst formation nor in embryo utilization of ART cycles. Slightly lower cumulative pregnancy (33% vs 39%) and live-birth (25% vs 30%) rates and higher miscarriage rate (53% and 29%) were observed in HPV + with respect to HPV − cycles. Fifty-five neonatal outcomes from HPV − ( n  = 45) and HPV + ( n  = 10) cycles were available. No stillbirths as well as no malformations were recorded. Conclusions This study confirmed previous findings that HPV DNA is present in semen of one quarter of infertile couples. No significant association of seminal HPV presence with semen parameters was found. We observed a trend of worst clinical outcomes in the HPV + group that is worth further investigation in a large population to draw definitive conclusions.

External otitis is a diffuse inflammation around the external auditory canal and auricle, which is often occurred by microbial infection. This disease is generally treated using antibiotics, but the frequent occurrence of antibiotic resistance requires the development of new antibiotic agents. In this context, unexplored bioactive natural candidates could be a chance for the production of targeted drugs provided with antimicrobial activity. In this paper, microbial pathogens were isolated from patients with external otitis using ear swabs for over one year, and the antimicrobial activity of the two methanol extracts from selected marine (Dunaliella salina) and freshwater (Pseudokirchneriella subcapitata) microalgae was tested on the isolated pathogens. Totally, 114 bacterial and 11 fungal strains were isolated, of which Staphylococcus spp. (28.8%) and Pseudomonas aeruginosa (P. aeruginosa) (24.8%) were the major pathogens. Only three Staphylococcus aureus (S. aureus) strains and 11 coagulase-negative Staphylococci showed resistance to methicillin. The two algal extracts showed interesting antimicrobial properties, which mostly inhibited the growth of isolated S. aureus, P. aeruginosa, Escherichia coli, and Klebsiella spp. with MICs range of 1.4 × 109 to 2.2 × 1010 cells/mL. These results suggest that the two algae have potential as resources for the development of antimicrobial agents.

The use of rapid molecular tests may anticipate the identification of causative agents and resistance determinants in the blood of critically ill patients with sepsis. From April to December 2021, all intensive care unit patients with sepsis or septic shock who were tested with the T2Bacteria and T2Resistance assays were included in a retrospective, single center study. The primary descriptive endpoints were results of rapid molecular tests and concomitant blood cultures. Overall, 38 combinations of T2Bacteria and T2Resistance tests were performed. One or more causative agent(s) were identified by the T2Bacteria assay in 26% of episodes (10/38), whereas negative and invalid results were obtained in 66% (25/38) and 8% (3/38) of episodes, respectively. The same pathogen detected by the T2Bacteria test grew from blood cultures in 30% of cases (3/10). One or more determinant(s) of resistance were identified by the T2Resistance assay in 11% of episodes (4/38). Changes in therapy based on T2Bacteria and/or T2Resistance results occurred in 21% of episodes (8/38). In conclusion, T2Bacteria/T2Resistance results can influence early treatment decisions in critically ill patients with sepsis or septic shock in real-life practice. Large, controlled studies remain necessary to confirm a favorable impact on patients’ outcomes and antimicrobial stewardship interventions.

The role of the recA and rnhA mutations on the growth of different thermo-sensitive mutants at the non permissive temperature was studied. The growth of Hfr strains selected by integrative suppression in a dnaA(Ts) mutant was found strongly dependent on the RecA protein. This latter gene product was also essential for gyrA(Ts) and gyrB(Ts), rnhA double mutants for growing at 43°C. This RecA+ dependent cell multiplication was due to the fact that all the strains studied initiated their DNA synthesis from site(s) different from the normal gene oriC. This phenomenon causes in the cell a non-stop production of the bacterial genome with concomitant disorders in the bacterial division process. It has been suggested that when the growth of the microorganism is driven by an extra-chromosomal genetic element it behaves like a transformed tumor cell. Thus the bacterial model may present many advantages for studying the mechanisms by which cells lose the control of their division process because of an infecting foreign genetic element integrated in their chromosome.

IntroductionCandida auris (C. auris) is an emerging nosocomial pathogen, and a sharp rise in cases of colonization and infection has been registered in intensive care units (ICUs) during the ongoing coronavirus disease 2019 (COVID-19) pandemic. The unfavorable resistance profile of C. auris and the potential high mortality of C. auris infections represent an important challenge for physicians.MethodsWe conducted a single-center retrospective study including all patients admitted to ICUs with isolation of C. auris in any non-sterile body site between February 20, 2020, and May 31, 2021. The primary aim of the study was to assess the cumulative incidence of C. auris candidemia in colonized patients. The secondary aim was to identify predictors of C. auris candidemia in the study population.ResultsDuring the study period, 157 patients admitted to ICUs in our hospital became colonized with C. auris; 59% of them were affected by COVID-19. Overall, 27 patients (17%) developed C. auris candidemia. The cumulative risk of developing C. auris candidemia was > 25% at 60 days after first detection of C. auris colonization. Seven patients with C. auris candidemia (26%) also developed a late recurrent episode. All C. auris blood isolates during the first occurring episode were resistant to fluconazole and susceptible to echinocandins, while 15 (56%) were resistant to amphotericin B. During late recurrent episodes, emergent resistance to caspofungin and amphotericin B occurred in one case each. In the final multivariable model, only multisite colonization retained an independent association with the development of C. auris candidemia.ConclusionCandida auris candidemia may occur in up to one fourth of colonized critically ill patients, and multisite colonization is an independent risk factor for the development of candidemia. Implementing adequate infection control measures remains crucial to prevent colonization with C. auris and indirectly the subsequent development of infection.

Purpose The global rise in infections due to multidrug-resistant Gram-negative bacteria (MDRGNB) infections has disproportionately impacted immunocompromised (IC) hosts. Cefiderocol, a novel siderophore cephalosporin, exhibits potent activity against MDRGNB, but limited data exist on its use in IC patients. This study aimed to describe cefiderocol use in IC patients. Methods Patients and therapy characteristics were descriptively reported, and outcomes were compared between IC and non-IC patients. Cox regression models were used to identify factors associated with mortality. Results Among 185 patients, 84 (45.4%) were IC. Similar descriptive rates were observed in IC and non-IC groups regarding indications for cefiderocol use, choice of monotherapy versus combination therapy, or empirical versus targeted treatment. The 28-day clinical cure rates were similar across patients receiving targeted cefiderocol therapy for infection due to Pseudomonas aeruginosa (81%, 17/21), Enterobacterales (77.3%, 17/22) and Acinetobacter baumannii (42%, 21/50). Thirty-day mortality was comparable between IC and non-IC patients (40.8%, 95% confidence interval [CI] 27.9–56.8 vs 33.3%, 95% CI 22.9–46.9; p = 0.5430). In multivariable analysis IC status was not associated with higher mortality. Conclusion Cefiderocol use in IC patients resulted in clinical outcomes comparable to non-IC patients when treating MDRGNB infections. IC status was not associated with an increased mortality, emphasising the importance of effective antimicrobial therapy. Further investigation is needed to clarify the relative impact of the administered treatment vs. the patients’ clinical condition in influencing the prognosis of Acinetobacter baumannii infections.

This study aimed to assess the predictors of acute kidney injury (AKI) during colistin therapy in a cohort of patients with bloodstream infections (BSI) due to colistin-susceptible Gram-negative bacteria, focusing on the role of serum albumin levels. The study consisted of two parts: (1) a multicentre retrospective clinical study to assess the predictors of AKI during colistin therapy, defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria; and (2) bioinformatic and biochemical characterization of the possible interaction between human serum albumin and colistin. Among the 170 patients included in the study, 71 (42%), 35 (21%), and 11 (6%) developed KDIGO stage 1 (K1-AKI), KDIGO stage 2 (K2-AKI), and KDIGO stage 3 (K3-AKI), respectively. In multivariable analyses, serum albumin <2.5 g/dL was independently associated with K1-AKI (subdistribution hazard ratio [sHR] 1.85, 95% confidence interval [CI] 1.17–2.93, p = 0.009) and K2-AKI (sHR 2.37, 95% CI 1.15–4.87, p = 0.019). Bioinformatic and biochemical analyses provided additional information nurturing the discussion on how hypoalbuminemia favors development of AKI during colistin therapy. In conclusion, severe hypoalbuminemia independently predicted AKI during colistin therapy in a large cohort of patients with BSI due to colistin-susceptible Gram-negative bacteria. Further study is needed to clarify the underlying causal pathways.

Background During June-July 2012, six imipenem-resistant Escherichia coli isolates were isolated from two patients hospitalized in a ward of one large tertiary-care hospital in Genoa, Italy. Genetic features associated with bla NDM-4 gene were investigated. Results The isolates exhibited the same PFGE profile and a multidrug-resistant (MDR) phenotype to aminoglycosides, fluoroquinolones, and β-lactams. The strains produced the NDM-4 carbapenemase and the bla NDM-4 gene was part of the variable region of a class 1 integron. MLST analysis revealed that all isolates belonged to sequence type 405 (ST405). Conclusions This is the first report on the emergence of an MDR strain of E.coli producing the NDM-4 MBL in Italy.

IntroductionCefiderocol is a siderophore cephalosporin showing activity against various carbapenem-resistant Gram-negative bacteria (CR-GNB). No data currently exist about real-world use of cefiderocol in terms of types of therapy (e.g., empirical or targeted, monotherapy or combined regimens), indications, and patient characteristics.MethodsIn this multicenter, prospective study, we aimed at describing the use of cefiderocol in terms of types of therapy, indications, and patient characteristics.ResultsCefiderocol was administered as empirical and targeted therapy in 27.5% (55/200) and 72.5% (145/200) of cases, respectively. Overall, it was administered as monotherapy in 101/200 cases (50.5%) and as part of a combined regimen for CR-GNB infections in the remaining 99/200 cases (49.5%). In multivariable analysis, previous isolation of carbapenem-resistant Acinetobacter baumannii odds ratio (OR) 2.56, with 95% confidence interval (95% CI) 1.01–6.46, p = 0.047] and previous hematopoietic stem cell transplantation (OR 8.73, 95% CI 1.05–72.54, p = 0.045) were associated with administration of cefiderocol as part of a combined regimen, whereas chronic kidney disease was associated with cefiderocol monotherapy (OR 0.38 for combined regimen, 95% CI 0.16–0.91, p = 0.029). Cumulative 30-day mortality was 19.8%, 45.0%, 20.7%, and 22.7% in patients receiving targeted cefiderocol for infections by Enterobacterales, A. baumannii, Pseudomonas aeruginosa, and any metallo-β-lactamase producers, respectively.ConclusionsCefiderocol is mainly used for targeted treatment, although empirical therapies account for more than 25% of prescriptions, thus requiring dedicated standardization and guidance. The almost equal distribution of cefiderocol monotherapy and cefiderocol-based combination therapies underlines the need for further study to ascertain possible differences in efficacy between the two approaches.