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Spotted fever group rickettsioses (SFGRs) are arthropod-borne diseases caused by obligate intracellular, gram-negative bacteria of the genus Rickettsia. SFGRs are associated with [approximately equal to] 20 species of Rickettsia, of [...]

This article discusses a case of fatal invasive pulmonary and cerebral aspergillosis caused by a triazole-resistant strain of Aspergillus fumigatus with multiple CYP51A mutations. Triazoles, such as voriconazole, are the primary treatment for invasive pulmonary aspergillosis, but triazole resistance in A. fumigatus has been increasing. The most common resistance mechanism is alterations in the CYP51A coding sequence or promoter. The patient in this case had autosomal recessive chronic granulomatous disease and had been treated with various antibiotics and voriconazole prophylaxis. Despite treatment with antifungal drugs, the patient's condition worsened and they eventually died. The isolated A. fumigatus strain had a CYP51A mutation with a 46 bp tandem repeat in the promoter and five amino acid substitutions in the coding sequence. This mutation has not been previously identified in clinical A. fumigatus isolates in Israel. It is unclear whether the mutated spores were acquired from the environment or due to prolonged voriconazole exposure. [Extracted from the article]

Objectives: To assess whether results of observational studies of potential anti-COVID-19 drugs were reproduced in subsequent randomized controlled trials (RCTs).Methods: This was a retrospective cross-sectional study, including studies published online between 1 January and 27 October 2020 that evaluated potential COVID-19 treatments and reported all-cause mortality.Results: Of 133 comparisons included in 117 studies, most were non-randomized (104/133, 78%). Hydroxychloroquine was the most common drug type, combined with azithromycin (n = 27, 20%) or alone (n = 22, 16%), followed by IL-6 inhibitors (n = 36, 27%) and corticosteroids (n = 26, 20%). Seventy-one percent (74/104) of non-randomized studies reported adjusted survival results and only 8% (8/104) adjusted for immortal time bias. Only two RCTs (2/29, 7%) reported significant survival benefit, both reporting treatment with corticosteroids, while 32/104 (31%) non-randomized studies showed statistically significant survival benefit associated with the intervention arm. The results of the majority (28/32, 88%) of non-randomized studies reporting survival benefit were not replicated by large-scale RCTs.Conclusions: The results of most non-randomized studies reporting survival benefit of potential anti-COVID-19 drugs were not replicated by large RCTs. Regulators and healthcare professionals should exercise caution and resist the pressure to approve and prescribe drugs of unproven efficacy and potential toxicity to optimize patient care and maintain public trust in medical science. [ABSTRACT FROM AUTHOR]

Background The optimal antibiotic regimen for Pseudomonas aeruginosa bacteremia is controversial. Although β-lactam monotherapy is common, data to guide the choice between antibiotics are scarce. We aimed to compare ceftazidime, carbapenems, and piperacillin-tazobactam as definitive monotherapy. Methods A multinational retrospective study (9 countries, 25 centers) including 767 hospitalized patients with P. aeruginosa bacteremia treated with β-lactam monotherapy during 2009–2015. The primary outcome was 30-day all-cause mortality. Univariate and multivariate, including propensity-adjusted, analyses were conducted introducing monotherapy type as an independent variable. Results Thirty-day mortality was 37/213 (17.4%), 42/210 (20%), and 55/344 (16%) in the ceftazidime, carbapenem, and piperacillin-tazobactam groups, respectively. Type of monotherapy was not significantly associated with mortality in either univariate, multivariate, or propensity-adjusted analyses (odds ratio [OR], 1.14; 95% confidence interval [CI], 0.52–2.46, for ceftazidime; OR, 1.3; 95% CI, 0.67–2.51, for piperacillin-tazobactam, with carbapenems as reference in propensity adjusted multivariate analysis; 542 patients). No significant difference between antibiotics was demonstrated for clinical failure, microbiological failure, or adverse events. Isolation of P. aeruginosa with new resistance to antipseudomonal drugs was significantly more frequent with carbapenems (36/206 [17.5%]) versus ceftazidime (25/201 [12.4%]) and piperacillin-tazobactam (28/332 [8.4%] (P =.007). Conclusions No significant difference in mortality, clinical, and microbiological outcomes or adverse events was demonstrated between ceftazidime, carbapenems, and piperacillin-tazobactam as definitive treatment of P. aeruginosa bacteremia. Higher rates of resistant P. aeruginosa after patients were treated with carbapenems, along with the general preference for carbapenem-sparing regimens, suggests using ceftazidime or piperacillin-tazobactam for treating susceptible infection. [ABSTRACT FROM AUTHOR]