Background. Extended-spectrum ß-lactamase (ESBL)—producing Enterobacteriaceae isolates are important clinical pathogens. In addition, the efficacy of cefepime for such infections is controversial. ...Methods. We performed a retrospective study of monomicrobial bacteremia caused by ESBL producers at 2 medical centers between May 2002 and August 2007. The patients definitively treated with in vitro active cefepime (cases) were compared with those treated with a carbapenem (controls) in a propensity score—matched analysis to assess therapeutic effectiveness. The 30-day crude mortality is the primary endpoint. Results. A total of 178 patients were eligible for the study. Patients who received cefepime (n = 17) as definitive therapy were more likely to have a clinical failure (odds ratio OR 6.2; 95% confidence interval CI, 1.7–22.5; P = .002), microbiological failure (OR 5.5; 95% CI, 1.3–25.6; P = .04), and 30-day mortality (OR 7.1; 95% CI, 2.5–20.3; P < .001) than those who received carbapenem therapy (n = 161). Multivariate regression revealed that a critical illness with a Pitt bacteremia score ≥4 points (OR 5.4; 95% CI, 1.4–20.9; P = .016), a rapidly fatal underlying disease (OR 4.4; 95% CI, 1.5–12.6; P = .006), and definitive cefepime therapy (OR 9.9; 95% CI, 2.8–31.9; P < .001) were independently associated with 30-day crude mortality. There were 17 case-control pairs in the propensity scores matched analysis. The survival analysis consistently found that individuals who received cefepime therapy had a lower survival rate (log-rank test, P = .016). Conclusions. Based on the current Clinical and Laboratory Standards Institute susceptible breakpoint of cefepime (minimum inhibitory concentration ≤8 μg/mL), cefepime definitive therapy is inferior to carbapenem therapy in treating patients with so-called cefepime-susceptible ESBL-producer bacteremia.
We conducted a longitudinal epidemiological surveillance of hypervirulent
(hvKP) in Taiwan. Bacteremic KP isolates collected from 16 hospitals in Taiwan between 2017 and 2019 were collected, and the ...virulent serotypes (K1, K2, K20, K54, and K57), antimicrobial susceptibilities, and virulence genes of these isolates were investigated. During the 3-year period, 1,310 bacteremic KP isolates were collected, of which 27.5% belonged to virulent serotypes, including K1 (
= 162), K2 (
= 74), K57 (
= 56), K54 (
= 41), and K20 (
= 27). K1 was the most prevalent capsular serotype, with an annual prevalence of 11-15%, and was equally distributed across the four geographic areas. The prevalence of K2 declined significantly in 2019. According to
-K typing results, 87% of K1 isolates were classified as
-1. Among K2 isolates,
72 (55.4%) and
-2 (41.9%) were the most common, whereas
-206 was the most prevalent (48.2%) among K57 isolates, followed by
-77 (25.0%).
-115 accounted for 85.4% of the K54 isolates, whereas
-95 accounted for 92.6% of K20 isolates.
was present in 99.4% of K1, 98.6% of K2, 89.3% of K57, 78.0% of K54, and 84.0% of K20 isolates.
was present in 100% of K1 and 98.6% of K2 isolates but was only present in 64.3% of K57, 58.5% of K54, and 74.1% of K20 isolates. K1 remains the dominant hvKP serotype and is associated with most virulence genes in Taiwan. Further studies are required to elucidate the significance of other virulent serotypes.
For the initial phase of pandemic of coronavirus disease 2019 (COVID-19), repurposing drugs that
inhibit severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have been attempted with ...overlooked or overestimated efficacy owing to limited clinical evidence. Most early clinical trials have the defects of study design, small sample size, non-randomized design, or different timings of treatment initiation. However, well-designed studies on asymptomatic or mild, or pediatric cases of COVID-19 are scarce and desperately needed to meet the clinical need. However, a trend could be observed based on current clinical evidence. Remdesivir and favipiravir may shorten the recovery time; lopinavir/ritonavir does not demonstrate treatment efficacy in severe patients. Triple therapy of ribavirin, lopinavir, and interferon β-1b showed early viral negative conversion, and the major effect may be related to interferon. Some small sample-size studies showed that interleukin-6 inhibitors may demonstrate clinical improvement; non-critical patients may benefit from convalescent plasma infusion in small sample-size studies; and the role of hydroxychloroquine or chloroquine in the treatment and prophylaxis of COVID-19 remains unclear. Combination therapy of traditional Chinese medicine with antiviral agents (ex. interferon, lopinavir, or arbidol) may alleviate inflammation in severe COVID-19 patients based on small sample-sized observational studies and experts' opinion. Most of the published studies included severe or critical patients with COVID-19. Combination therapy of antiviral agents and immune-modulating drugs is reasonable especially for those critical COVID-19 patients with cytokine release syndrome. Drugs to blunt cytokine release might not benefit for patients in the early stage with mild disease or the late stage with critical illness. Traditional Chinese medicine with antiviral effects on SARS-CoV-2 and immune-modulation is widely used for COVID-19 patients in China, and is worthy of further studies. In this review, we aim to highlight the available therapeutic options for COVID-19 based on current clinical evidence and encourage clinical trials specific for children and for patients with mild disease or at the early stage of COVID-19.
To explore the in vitro antimicrobial susceptibility among clinically important Gram-negative bacteria (GNB) in Taiwan.
From 2016 through 2018, a total of 5458 GNB isolates, including Escherichia ...coli (n = 1545), Klebsiella pneumoniae (n = 1255), Enterobacter species (n = 259), Pseudomonas aeruginosa (n = 1127), Acinetobacter baumannii complex (n = 368), and Stenotrophomonas maltophilia (n = 179), were collected. The susceptibility results were summarized by the breakpoints of minimum inhibitory concentration (MIC) of CLSI 2020, EUCAST 2020 (for colistin), or published articles (for ceftolozane/tazobactam). The resistance genes among multidrug-resistant (MDR) or extensively drug-resistant (XDR)-GNB were investigated by multiplex PCR.
Significantly higher rates of non-susceptibility (NS) to ertapenem and carbapenemase production, predominantly KPC and OXA-48-like beta-lactamase, were observed in Enterobacterales isolates causing respiratory tract infection than those causing complicated urinary tract or intra-abdominal infection (12.7%/3.44% vs. 5.7%/0.76% or 7.7%/0.97%, respectively). Isolates of Enterobacter species showed higher rates of phenotypic extended-spectrum β-lactamase and NS to ertapenem than E. coli or K. pneumoniae isolates. Although moderate activity (54–83%) was observed against most potential AmpC-producing Enterobacterales isolates, ceftolozane/tazobactam exhibited poor in vitro (44.7–47.4%) activity against phenotypic AmpC Enterobacter cloacae isolates. Additionally, 251 (22.3%) P. aeruginosa isolates exhibited the carbapenem-NS phenotype, and their MDR and XDR rate was 63.3% and 33.5%, respectively. Fifteen (75%) of twenty Burkholderia cenocepacia complex isolates were inhibited by ceftolozane/tazobactam at MICs of ≤4 μg/mL.
With the increase in antibiotic resistance in Taiwan, it is imperative to periodically monitor the susceptibility profiles of clinically important GNB.
•Enterobacter isolates showed 3.2% non-susceptible to both CZA and TGC.•CZA resistance was prominent in India (16.5%), Guatemala (15.4%), and the Philippines (13.1%).•Carbapenem resistance rose from ...2.9% (2014–2017) to 4.3% (2018–2021).•Asia had the highest CZA resistance (87.4%) among carbapenem-resistant Enterobacter isolates.•The prevalent carbapenemases were blaNDM (59.2%) and blaVIM (24.2%).
Trends in the susceptibility to ceftazidime-avibactam (CZA) and tigecycline (TGC) among Enterobacter species from different geographic areas are unknown.This study aimed to analyse the trends in CZA and TGC susceptibility changes across different continents from 2014 to 2021 utilizing Antimicrobial Testing Leadership and Surveillance (ATLAS) data.
A total of 23 669 isolates of Enterobacter species were collected over an 8-y period.
The overall non-susceptibility rate of Enterobacter isolates to both CZA and TGC was 3.2%. India (16.5%), Guatemala (15.4%), and the Philippines (13.1%) exhibited the highest resistance to CZA. The increase in CZA resistance rates was particularly evident in Asia, with an increase from 4.0% to 8.3%, and in Latin America, from 1.5% to 5%. The non-susceptibility rate for TGC mildly increased in Africa/Middle East but decreased in other continents during the study period. The overall rate of carbapenem resistance increased from 2.9% in 2014–2017 to 4.3% in 2018–2021. Among carbapenem-resistant Enterobacter isolates, the CZA resistance rate was highest in Asia (87.4%), followed by Europe (69.2%) and Africa/Middle East (60.8%). Among the 380 Enterobacter isolates resistant to CZA and carbapenem, the most common genotype of carbapenemase genes was blaNDM (59.2%), followed by blaVIM (24.2%), blaOXA (4.2%), blaIMP (1.1%), and blaKPC (1.1%). The susceptibility of carbapenem-resistant Enterobacter to TGC remained high, with an overall susceptibility rate of 90%.
The heterogeneous distribution of CZA resistance rates among different geographical regions highlights the divergent therapeutic options for drug-resistant Enterobacter species.
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Background. Since 1986, researchers have noted a syndrome of Klebsiella pneumoniae pyogenic liver abscess that is complicated by endophthalmitis or central nervous system infections. There are ...limited data regarding the role of bacterial genotype in the pathogenesis of this syndrome. Methods. We conducted a retrospective cohort study involving 177 cases of K. pneumoniae pyogenic liver abscess treated during 1997–2005 at a tertiary university hospital in Taiwan. We performed bacterial cps genotyping by polymerase chain reaction detection of serotype-specific alleles at wzy and wzx loci and used an in vitro serum assay to evaluate the virulence of bacterial strains. Results. Septic ocular or central nervous system complications developed in 23 patients (13%). Logistic regression analysis showed that genotype K1 was the only significant risk factor (adjusted odds ratio, 4.8; 95% confidence interval, 1.5–15.7, P = .009). The serum resistance assay indicated that, on average, K1 strains (n = 100) were significantly more virulent than were strains of K2 (n = 36), K20/K5/K54 (n = 21), or other genotypes (n = 20) (P <t; .001 for each comparison). In addition to the serotype-specific cps region, the genomic background of K1 strains also differed significantly from that of non-K1 strains (20-kb kfu/PTS region, 97/100 vs. 13/77; P <t; .001). of the 19 cases in which genotype K1 strains caused complications, 8 patients (42%) did not have identifiable underlying medical diseases. Conclusions. K. pneumoniae genotype K1 is an emerging pathogen capable of causing catastrophic septic ocular or central nervous system complications from pyogenic liver abscess independent of underlying diseases in the host.
Abstract
Objectives
We performed a systematic review and network meta-analysis of randomized controlled trials (RCTs) to provide updated information regarding the clinical efficacy of remdesivir in ...treating coronavirus disease 2019 (COVID-19).
Methods
PubMed, Embase, Cochrane Library, clinical trial registries of ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform were searched for relevant articles published up to 18 November 2020.
Results
Five RCTs, including 13 544 patients, were included in this meta-analysis. Among them, 3839 and 391 patients were assigned to the 10 day and 5 day remdesivir regimens, respectively. Patients receiving 5 day remdesivir therapy presented greater clinical improvement than those in the control group OR = 1.68 (95% CI 1.18–2.40), with no significant difference observed between the 10 day and placebo groups OR = 1.23 (95% CI 0.90–1.68). Patients receiving remdesivir revealed a greater likelihood of discharge 10 day remdesivir versus control: OR = 1.32 (95% CI 1.09–1.60); 5 day remdesivir versus control: OR = 1.73 (95% CI 1.28–2.35) and recovery 10 day remdesivir versus control: OR = 1.29 (95% CI 1.03–1.60); 5 day remdesivir versus control: OR = 1.80 (95% CI 1.31–2.48) than those in the control group. In contrast, no mortality benefit was observed following remdesivir therapy. Furthermore, no significant association was observed between remdesivir treatment and an increased risk of adverse events.
Conclusions
Remdesivir can help improve the clinical outcome of hospitalized patients with COVID-19 and a 5 day regimen, instead of a 10 day regimen, may be sufficient for treatment. Moreover, remdesivir appears as tolerable as other comparators or placebo.
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