Fluoroquinolones vs Macrolides in the Treatment of Legionnaires Disease

Sabrià, Miquel; Pedro‐Botet, María Luisa; Gómez, Joaquín Gómez; Roig, Jordi; Vilaseca, Blanca; Sopena, Nieves; Baños, V.

doi:10.1378/chest.128.3.1401

Cited by 132 publications

(68 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…pneumophila is a facultative intracellular pathogen. Hence, antimicrobial agents capable of achieving intracellular concentra- tions higher than the in vitro bacterial MICs (e.g., tetracyclines, macrolides, rifampin, and fluoroquinolones) are usually recommended for the treatment of legionellosis, rather than antibiotics with poor intracellular penetration (28). Despite the use of these antimicrobial agents and the improvement of diagnostic methods allowing early detection of infections, the mortality rate among legionellosis patients remains elevated (10 to 30%) (13).…”

Section: Discussionmentioning

confidence: 99%

Antimicrobial Activity of Solithromycin against Clinical Isolates of Legionella pneumophila Serogroup 1

Mallegol

Fernandes

Melano

et al. 2014

Antimicrob Agents Chemother

View full text Add to dashboard Cite

The activity of solithromycin was evaluated against clinical Legionella pneumophila serogroup 1 (Lp1) isolates (n ‫؍‬ 196) collected in Ontario, Canada, from 1980 to 2011. Its in vitro activity was compared to that of azithromycin (AZM) using the broth microdilution method. Solithromycin had a MIC 50 of <0.015 g/ml and a MIC 90 of 0.031 g/ml, making its activity at least 8-fold to 32-fold higher than that of AZM (MIC 50 and MIC 90 , 0.125 g/ml and 1 g/ml, respectively). Ninety-nine percent of the isolates had MICs for solithromycin ranging from <0.015 g/ml to 0.031 g/ml, whereas 83.6% of the isolates showed MICs for AZM ranging from 0.062 g/ml to 0.25 g/ml. Interestingly, 96.7% (30 out of 31 clinical isolates) identified with higher AZM MICs (0.5 g/ml to 2 g/ml) belonged to the clinically prevalent sequence type 1. To investigate the intracellular activity of solithromycin, in vitro invasion assays were also performed against a subset of representative Lp1 isolates internalized within human lung epithelial cells. Solithromycin and AZM both inhibited growth of all intracellular Lp1 isolates at 1؋ or 8؋ MICs, displaying bacteriostatic effects, as would be expected with protein synthesis inhibitor rather than bactericidal activity. Solithromycin demonstrated the highest in vitro and intracellular potency against all Lp1 isolates compared to AZM. Given the rapid spread of resistance mechanisms among respiratory pathogens and the reported treatment failures in legionellosis, the development of this new fluoroketolide, already in phase 3 oral clinical studies, constitutes a promising alternative option for the treatment of legionellosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Antimicrobial Activity of Solithromycin against Clinical Isolates of Legionella pneumophila Serogroup 1

Mallegol

Fernandes

Melano

et al. 2014

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…As Legionella spp. are obligatory intracellular bacteria, they are unaffected by beta-lactam antibiotics and require specific treatment with high-dose quinolones or macrolides (7). Treatment providing coverage against Legionella spp.…”

mentioning

confidence: 99%

Diagnostic Accuracy of PCR Alone and Compared to Urinary Antigen Testing for Detection of Legionella spp.: a Systematic Review

et al. 2016

View full text Add to dashboard Cite

bThe diagnosis of Legionnaires' disease (LD) is based on the isolation of Legionella spp., a 4-fold rise in antibodies, a positive urinary antigen (UA), or direct immunofluorescence tests. PCR is not accepted as a diagnostic tool for LD. This systematic review assesses the diagnostic accuracy of PCR in various clinical samples with a direct comparison versus UA. We included prospective or retrospective cohort and case-control studies. Studies were included if they used the Centers for Disease Control and Prevention consensus definition criteria of LD or a similar one, assessed only patients with clinical pneumonia, and reported data for all true-positive, false-positive, true-negative, and false-negative results. Two reviewers abstracted data independently. Risk of bias was assessed using Quadas-2. Summary sensitivity and specificity values were estimated using a bivariate model and reported with a 95% confidence interval (CI). Thirty-eight studies were included. A total of 653 patients had confirmed LD, and 3,593 patients had pneumonia due to other pathogens. The methodological quality of the studies as assessed by the Quadas-2 tool was poor to fair. The summary sensitivity and specificity values for diagnosis of LD in respiratory samples were 97.4% (95% CI, 91.1% to 99.2%) and 98.6% (95% CI, 97.4% to 99.3%), respectively. These results were mainly unchanged by any covariates tested and subgroup analysis. The diagnostic performance of PCR in respiratory samples was much better than that of UA. Compared to UA, PCR in respiratory samples (especially in sputum samples or swabs) revealed a significant advantage in sensitivity and an additional diagnosis of 18% to 30% of LD cases. The diagnostic performance of PCR in respiratory samples was excellent and preferable to that of the UA. Results were independent on the covariate tested. PCR in respiratory samples should be regarded as a valid tool for the diagnosis of LD.) is a life-threatening pulmonary infection. The most common species causing clinical disease in humans is Legionella pneumophila (1). In addition to L. pneumophila, 19 species are documented as human pathogens on the basis of their isolation from clinical specimens (2). LD can affect people both in the community (3) and in the hospital and, in both settings, can occur in outbreaks (4, 5). The true incidence of LD is difficult to assess, because the bacterial etiology for community-acquired pneumonia (CAP) is generally not documented in clinical practice. LD cannot be differentiated clinically or radiographically from CAP caused by other bacterial pathogens (6). As Legionella spp. are obligatory intracellular bacteria, they are unaffected by beta-lactam antibiotics and require specific treatment with high-dose quinolones or macrolides (7). Treatment providing coverage against Legionella spp. has been shown to improve clinical success (8). Thus, early diagnosis of LD is important and can have an effect on both public health and management in hospitals (9, 10).Conventional methods for the diagnosis of LD ...

show abstract

“…While this gene has remained functionally uncharacterized, Legionella sp. have been reported to show resistance to a range of different antibiotics, including nalidixic acid (21), streptomycin (21), and clindamycin (45), with sensitivities reported for rifamycins, macrolides, fluoroquinolones (19,43,48), and ampicillin (32).…”

Section: Resultsmentioning

confidence: 99%

Characterization and Quantitation of a Novel β-Lactamase Gene Found in a Wastewater Treatment Facility and the Surrounding Coastal Ecosystem

Uyaguari

Fichot

Scott

et al. 2011

Appl Environ Microbiol

View full text Add to dashboard Cite

Wastewater treatment plants (WWTPs) are engineered structures that collect, concentrate, and treat human waste, ultimately releasing treated wastewater into local environments. While WWTPs efficiently remove most biosolids, it has been shown that many antibiotics and antibiotic-resistant bacteria can survive the treatment process. To determine how WWTPs influence the concentration and dissemination of antibiotic-resistant genes into the environment, a functional metagenomic approach was used to identify a novel antibiotic resistance gene within a WWTP, and quantitative PCR (qPCR) was used to determine gene copy numbers within the facility and the local coastal ecosystem. From the WWTP metagenomic library, the fosmid insert contained in one highly resistant clone (MIC, ϳ416 g ml ؊1 ampicillin) was sequenced and annotated, revealing 33 putative genes, including a 927-bp gene that is 42% identical to a functionally characterized ␤-lactamase from Staphylococcus aureus PC1. Isolation and subcloning of this gene, referred to as bla M-1 , conferred ampicillin resistance to its Escherichia coli host. When normalized to volume, qPCR showed increased concentrations of bla M-1 during initial treatment stages but 2-fold-decreased concentrations during the final treatment stage. The concentration ng ؊1 DNA increased throughout the WWTP process from influent to effluent, suggesting that bla M-1 makes up a significant proportion of the overall genetic material being released into the coastal ecosystem. Average discharge was estimated to be 3.9 ؋ 10 14 copies of the bla M-1 gene released daily into this coastal ecosystem. Furthermore, the gene was observed in all sampled coastal water and sediment samples surrounding the facility. Our results suggest that WWTPs may be a pathway for the dissemination of novel antibiotic resistance genes into the environment.

show abstract

Fluoroquinolones vs Macrolides in the Treatment of Legionnaires Disease

Cited by 132 publications

References 27 publications

Antimicrobial Activity of Solithromycin against Clinical Isolates of Legionella pneumophila Serogroup 1

Antimicrobial Activity of Solithromycin against Clinical Isolates of Legionella pneumophila Serogroup 1

Diagnostic Accuracy of PCR Alone and Compared to Urinary Antigen Testing for Detection of Legionella spp.: a Systematic Review

Characterization and Quantitation of a Novel β-Lactamase Gene Found in a Wastewater Treatment Facility and the Surrounding Coastal Ecosystem

Contact Info

Product

Resources

About