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Objectives We aimed to describe the clinical outcomes and duration of viral shedding in high-risk patients with haematological malignancies hospitalized with COVID-19 during Omicron variant predominance who received early treatment with antivirals. Methods We conducted a prospective observational study on high-risk haematological patients admitted in our hospital between December 2021 and March 2022. We performed detection techniques on viral subgenomic mRNAs until negative results were obtained to document active, prolonged viral replication. Results This analysis included 60 consecutive adults with high-risk haematological malignancies and COVID-19. All of these patients underwent early treatment with remdesivir. Thirty-two (53%) patients received combined antiviral strategies, with sotrovimab or hyperimmune plasma being added to remdesivir. The median length of viral replication—as measured by real-time RT-PCR and/or subgenomic RNA detection—was 20 (IQR 14–28) days. Prolonged viral replication (6 weeks after diagnosis) was documented in six (10%) patients. Only two patients had prolonged infection for more than 2 months. Overall mortality was 5%, whereas COVID-19-related mortality was 0%. Conclusions Current outcomes of high-risk patients with haematological malignancies hospitalized with COVID-19 during Omicron variant predminance are good with the use of early antiviral strategies. Persistent viral shedding is uncommon. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus is a major human pathogen causing a vast array of infections with significant mortality. Its versatile physiology enables it to adapt to various environments. Specific physiological changes are thought to underlie the frequent failure of antimicrobial therapy despite susceptibility in standard microbiological assays. Bacteria capable of surviving high antibiotic concentrations despite having a genetically susceptible background are described as 'antibiotic tolerant'. In this review, we put current knowledge on environmental triggers and molecular mechanisms of increased antibiotic survival of S. aureus into its clinical context. We discuss animal and clinical evidence of its significance and outline strategies to overcome infections with antibiotic-tolerant S. aureus. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the influence on mortality of empirical double-active combination antimicrobial therapy (DACT) compared with active monotherapy (AM) in septic shock patients.Methods: A retrospective study was performed of monomicrobial septic shock patients admitted to a university centre during 2010-15. A propensity score (PS) was calculated using a logistic regression model taking the assigned therapy as the dependent variable, and used as a covariate in multivariate analysis predicting 7, 15 and 30 day mortality and for matching patients who received DACT or AM. Multivariate models comprising the assigned therapy group and the PS were built for specific patient subgroups.Results: Five-hundred and seventy-six patients with monomicrobial septic shock who received active empirical antimicrobial therapy were included. Of these, 340 received AM and 236 DACT. No difference in 7, 15 and 30 day all-cause mortality was found between groups either in the PS-adjusted multivariate logistic regression analysis or in the PS-matched cohorts. However, in patients with neutropenia, DACT was independently associated with a better outcome at 15 (OR 0.29, 95% CI 0.09-0.92) and 30 (OR 0.25, 95% CI 0.08-0.79) days, while in patients with Pseudomonas aeruginosa infection DACT was associated with lower 7 (OR 0.12, 95% CI 0.02-0.7) and 30 day (OR 0.26, 95% CI 0.08-0.92) mortality.Conclusions: All-cause mortality at 7, 15 and 30 days was similar in patients with monomicrobial septic shock receiving empirical double-active combination therapy and active monotherapy. However, a beneficial influence of empirical double-active combination on mortality in patients with neutropenia and those with P. aeruginosa infection is worthy of further study. [ABSTRACT FROM AUTHOR]

Objectives: Early prosthetic joint infections (PJIs) are managed with debridement, implant retention and antibiotics (DAIR). Our aim was to evaluate risk factors for failure after stopping antibiotic treatment.Methods: From 1999 to 2013, early PJIs managed with DAIR were prospectively collected and retrospectively reviewed. The main variables potentially associated with outcome were gathered, and the minimum follow-up was 2 years. For the present study, only patients who were in remission after one debridement and without long-term antibiotic suppression were included. The primary endpoint was implant removal or the need to reintroduce antibiotic treatment due to failure.Results: One-hundred-and-forty-three patients met the inclusion criteria. The failure rate after a median duration of oral antibiotic treatment of 69 days (IQR 45-95 days) was 11.8%. In 92 cases, PJI was due to Gram-positive microorganisms, in 21 cases PJI was due to Gram-negative microorganisms and in 30 cases PJI was due to a polymicrobial infection with both Gram-positive and Gram-negative microorganisms. In Gram-positive infections, rifampicin administered in combination with linezolid, co-trimoxazole or clindamycin was associated with a higher failure rate (27.8%, P = 0.026) than that in patients receiving a combination of rifampicin with levofloxacin, ciprofloxacin or amoxicillin (8.3%) or monotherapy with linezolid or co-trimoxazole (0%). Among patients with a Gram-negative infection, the use of fluoroquinolones was associated with a lower failure rate (7.1% versus 37.5%, P = 0.044).Conclusions: The only factor associated with failure was the oral antibiotic selection, not the duration of treatment. Linezolid, co-trimoxazole and clindamycin, but not levofloxacin, serum concentrations are reduced by rifampicin; a fact that could explain our findings. Further studies monitoring serum concentration could help to improve the efficacy of these antibiotics when administered in combination with rifampicin. [ABSTRACT FROM AUTHOR]

Objectives Gram-positive microorganisms have been the predominant pathogens in central venous catheter-related bloodstream infections (CRBSIs). Recent guidelines recommend empirical therapy according to this and restrict coverage for Gram-negatives to specific circumstances. This study aimed to analyse the epidemiological changes in CRBSIs over the 1991–2008 period and to analyse predictors of Gram-negative CRBSIs. Patients and methods A prospectively collected cohort of patients with confirmed CRBSIs was analysed. Strains isolated and antimicrobial susceptibility, as well as clinical and demographic variables were recorded. Differences observed during the study period were analysed by means of a χ2 trend test and factors associated with Gram-negative CRBSIs by means of multivariable analysis. Results Between 1991 and 2008, 1129 episodes of monomicrobial CRBSIs were recorded. There was an increase in the incidence of CRBSIs, from 0.10 (1991–92) to 0.31 (2007–08) episodes/1000 patient-days. A significant increase in the number of Gram-negative strains among the total isolates was also found, from 3 (4.7%) in 1991–92 to 70 (40.23%) in 2007–08, with a parallel decrease in the percentage of Gram-positives. Solid organ transplantation, prior use of penicillins and hospital stay longer than 11 days were independently associated with a significantly higher risk of Gram-negative CRBSIs, while cirrhosis, diabetes and use of quinolones were associated with a higher risk of Gram-positives. Conclusions Gram-negative strains are an increasing cause of CRBSIs, reaching a prevalence of 40% in the 2007–08 period in our hospital. If this trend is confirmed in other centres, a broad-spectrum empirical therapy should be considered in managing these infections. [ABSTRACT FROM PUBLISHER]

Background: The increasing prevalence of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae will probably trigger a rise in the use of carbapenems. The effect of these antibiotics on the risk of involvement of ESBL-producing organisms in serious infections is unclear.Methods: Retrospective analysis of 2172 episodes of healthcare-associated bacteraemia diagnosed during a 3 year period in a teaching hospital. Putative risk factors included demographics, co-morbidities, previous isolation of an ESBL-producing organism and exposure to antibiotics. Univariate and multivariate analysis of the association of risk factors with ESBL-producing organisms was performed in the entire series of bacteraemic episodes and in those due to Escherichia coli or Klebsiella spp.Results: In the entire series, prior isolation of an ESBL-producing organism [odds ratio (OR) 5.9 (3.02, 11.5)]; an ultimately/finally fatal co-morbidity [OR 2.8 (1.55, 4.95)]; renal transplantation [OR 4.3 (1.96, 9.63)]; a urinary source [OR 4.2 (2.22, 7.84)]; shock [OR 2.4 (1.35, 4.1)] and previous use of cephalosporins [OR 2.6 (1.54, 4.51)], carbapenems [OR 2.5 (1.24, 5.05)] and glycopeptides [OR 0.4 (0.13, 0.93)] were significantly associated with ESBL-producing E. coli or Klebsiella spp. by multivariate analysis. Prior isolation of an ESBL-producing organism, an ultimately/finally fatal co-morbidity, renal transplantation, and previous use of cephalosporins and carbapenems were also significant in the analysis restricted to episodes due to E. coli or Klebsiella spp.Conclusions: In patients with healthcare-associated bacteraemia, prior use of carbapenems may be only second to cephalosporins as the most significant antibiotic exposure associated with the involvement of ESBL-producing organisms. [ABSTRACT FROM PUBLISHER]

The in vitro activity of clinafloxacin was studied in comparison with ciprofloxacin, levofloxacin, moxifloxacin, nalidixic acid, sparfloxacin and trovafloxacin against Acinetobacter baumannii clinical isolates. Clinafloxacin showed a MIC(90) of 4 mg/L, whereas the remaining quinolones showed a MIC(90) equal to or higher than 16 mg/L. MIC(50) determination in the presence of reserpine resulted in a two-fold decrease, except for trovafloxacin, which decreased four-fold, and for moxifloxacin and nalidixic acid, which did not change. The effect of reserpine was most pronounced among strains with a low level of resistance to quinolones. The MIC of clinafloxacin for strains with no mutation in either gyrA or parC genes ranged from 0.008 to 0.25 mg/L. In strains with a single mutation at amino acid codon Ser83 of the gyrA gene, the MIC of clinafloxacin ranged from 0.12 to 1 mg/L, whereas strains with a double mutation, one in the gyrA gene and another in the parC gene, showed a range of MIC of clinafloxacin from 1 to 8 mg/L. Therefore, clinafloxacin shows good activity against strains carrying a single mutation in the gyrA gene, and hence a second mutation is required for the microorganism to express resistance. [ABSTRACT FROM AUTHOR]

The emergence and evolution of quinolone-resistant Escherichia coli in faeces of patients with prostatitis treated with high-dose oral ciprofloxacin for 1 month were studied. In 11 of 23 patients, from whom only quinolone-susceptible E. coli was isolated before treatment, quinolone-resistant strains, genetically distinct from the quinolone-susceptible ones, predominated during and just after therapy. Two months after treatment, these were completely displaced by quinolone-susceptible E. coli, genetically distinct from the E. coli isolated before and during therapy. Hence, during ciprofloxacin therapy, half of the patients were transiently colonized with new, quinolone-resistant strains of E. coli. [ABSTRACT FROM AUTHOR]

This study assessed the efficacy of oral josamycin 1 g bd for five days as treatment for non-severe, community-acquired pneumonia in patients less than 60 years of age who were not at obvious risk of developing respiratory tract infection caused by aerobic Gram-negative bacilli. Of the 84 patients (43 male, 41 female) with a mean age of 33 years who were enrolled during a 14-month period, the clinical outcome was invariabily favourable. All patients became afebrile within three days of starting therapy; the mean duration of fever after initiating treatment was 1·7 days. Therefore, according to the study protocol, josamycin therapy was discontinued on day five. A chest X-ray performed four to six weeks after completing treatment was normal in every case and no relapses were observed during a six-week follow-up period. We conclude that a five-day course of josamycin is effective monotherapy for community-acquired pneumonia in patients without the clinical features of severe infection. [ABSTRACT FROM PUBLISHER]

Objectives To determine whether time-to-positivity (TTP) in aerobic and anaerobic blood culture vials is useful to predict the presence of Candida glabrata in patients with candidaemia. Methods TTP was recorded for both aerobic and anaerobic vials for each blood culture set of monomicrobial candidaemia. We considered TTP as the shortest time registered for any positive vial. Two diagnostic criteria were evaluated: the cut-off TTP value as obtained from a receiver operating characteristic curve and the detection of growth only or with a shorter TTP in anaerobic vials. Results A total of 157 episodes were analysed of which 19 (12.1%) were due to C. glabrata. The TTP for C. glabrata was longer than that for other species. C. glabrata grew more frequently than other species in anaerobic vials [9/19 (47%) versus 19/138 (14%); P = 0.001] and also more often exclusively or earlier in anaerobic vials [7/19 (37%) versus 5/138 (4%); P < 0.0001]. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of a TTP >56.5 h for predicting the presence of C. glabrata were 47%, 88%, 36% and 92%, respectively. Growth detection only or earlier in anaerobic flasks had a sensitivity of 37%, a specificity of 96%, a PPV of 58% and an NPV of 92%. Conclusions Using the BACTEC 9240 system, a TTP ≤56.5 h is useful to rule out C. glabrata. In addition, in settings with an ∼12% prevalence of C. glabrata candidaemia, yeast detection exclusively or earlier in anaerobic vials increases the probability of the presence of C. glabrata to 58%, which may be useful for early treatment optimization. [ABSTRACT FROM PUBLISHER]

A response by Alex Soriano and colleagues, to a letter to the editor about their article on the epidemiology of venous catheter-related bloodstream infections is presented.