Antimicrobial agents and chemotherapy
-
Antimicrob. Agents Chemother. · Dec 2017
Sustained Ex Vivo Susceptibility of Plasmodium falciparum to Artemisinin Derivatives but Increasing Tolerance to Artemisinin Combination Therapy Partner Quinolines in The Gambia.
Antimalarial interventions have yielded a significant decline in malaria prevalence in The Gambia, where artemether-lumefantrine (AL) has been used as a first-line antimalarial for a decade. Clinical Plasmodium falciparum isolates collected from 2012 to 2015 were analyzed ex vivo for antimalarial susceptibility and genotyped for drug resistance markers (pfcrt K76T, pfmdr1 codons 86, 184, and 1246, and pfk13) and microsatellite variation. Additionally, allele frequencies of single nucleotide polymorphisms (SNPs) from other drug resistance-associated genes were compared from genomic sequence data sets from 2008 (n = 79) and 2014 (n = 168). ⋯ The TNYD (pfcrt 76T and pfmdr1 NYD wild-type haplotype) also increased in frequency following AL implementation in 2008. These results suggest selection for pfcrt and pfmdr1 genotypes that enable tolerance to lumefantrine. Increased tolerance to lumefantrine calls for sustained chemotherapeutic monitoring in The Gambia to minimize complete artemisinin combination therapy (ACT) failure in the future.
-
Antimicrob. Agents Chemother. · Dec 2017
Whole-Transcriptome and -Genome Analysis of Extensively Drug-Resistant Mycobacterium tuberculosis Clinical Isolates Identifies Downregulation of ethA as a Mechanism of Ethionamide Resistance.
Genetics-based drug susceptibility testing has improved the diagnosis of drug-resistant tuberculosis but is limited by our lack of knowledge of all resistance mechanisms. Next-generation sequencing has assisted in identifying the principal genetic mechanisms of resistance for many drugs, but a significant proportion of phenotypic drug resistance is unexplained genetically. Few studies have formally compared the transcriptomes of susceptible and resistant Mycobacterium tuberculosis strains. ⋯ These results demonstrate a new mechanism of ethionamide resistance that can cause high-level resistance when it is combined with other ethionamide resistance-conferring mutations. Our study revealed many other genes which were highly up- or downregulated in XDR strains, including a toxin-antitoxin module (mazF5 mazE5) and tRNAs (leuX and thrU). This suggests that global transcriptional modifications could contribute to resistance or the maintenance of bacterial fitness have also occurred in XDR strains.
-
Antimicrob. Agents Chemother. · Dec 2017
Age-Related Trends in Adults with Community-Onset Bacteremia.
To understand the epidemiological variation in bacteremia characteristics among differently aged populations, adults with community-onset bacteremia during a 6-year period were studied in a retrospective cohort. A total of 2,349 bacteremic patients were stratified into four age categories: young adults (18 to 44 years old; 196 patients; 8.3%), adults (45 to 64 years old; 707 patients; 30.1%), the elderly (65 to 84 years old; 1,098 patients; 46.7%), and the oldest old (≥85 years old; 348 patients; 14.8%). Age-related trends in critical illness (a Pitt bacteremia score of ≥4) at bacteremia onset, antibiotic-resistant pathogens (extended-spectrum β-lactamase [ESBL]-producing Escherichia coli, Klebsiella species, and Proteus mirabilis [EKP]; methicillin-resistant Staphylococcus aureus [MRSA]; and levofloxacin nonsusceptible EKP), inappropriate empirical antibiotic therapy (EAT), and 4-week mortality rate were observed. ⋯ Moreover, ESBL-producing EKP (AOR, 12.94; P < 0.001), MRSA (AOR, 8.66; P < 0.001), and levofloxacin-nonsusceptible EKP (AOR, 4.27; P < 0.001) were linked to inappropriate EAT. In conclusion, among adults with community onset bacteremia, significant positive age-related trends were noted in antibiotic-resistant pathogens and bacteremia severity, which were related to the increasing incidence of inappropriate EAT and 4-week mortality with age. Thus, different empirical antimicrobial regimens should be considered for distinct age groups.
-
Antimicrob. Agents Chemother. · Dec 2017
Observational StudyA Cohort Study of Risk Factors That Influence Empirical Treatment of Patients with Acute Pyelonephritis.
The aim of the current study was to compare community-acquired acute pyelonephritis (CA-APN) with health care-associated acute pyelonephritis (HCA-APN), describe the outcomes, and identify variables that could predict antimicrobial susceptibility. We conducted an observational study that included all consecutive episodes of acute pyelonephritis (APN) in adults during 2014 at a Spanish university hospital. From each episode, demographic data, comorbidities, clinical presentation, microbiological data, antimicrobial therapy, and outcome were recorded. ⋯ Relapse rates were significantly higher when definitive antimicrobial treatment was not adequate (37.1% versus 9.3% when definitive antimicrobial treatment was adequate; P < 0.001). Our study reflects the rise of resistance to commonly used antibiotics in acute pyelonephritis. In order to choose the adequate empirical antibiotic therapy, risk factors for resistance should be considered.