Persistently Positive Culture Results in a Patient with Community-Acquired Pneumonia Due to Legionella pneumophila

Tan, James S.; File, Thomas M.; DiPersio, Joseph R.; DiPersio, Linda P.; Hamor, Robert H.; Saravolatz, Louis D.; Stout, Janet E.

doi:10.1086/320526

Cited by 18 publications

(10 citation statements)

References 23 publications

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“…Macrolides are the first-line antibiotics for LD therapy (6,7). Treatment failures have been reported, suggesting the possibility of resistance acquired in vivo (8,9). Yet no macrolide-resistant clinical strain has been isolated so far.…”

Section: Discussionmentioning

confidence: 99%

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Ribosomal Mutations Conferring Macrolide Resistance in Legionella pneumophila

Descours

Ginevra

Jacotin

et al. 2017

Antimicrob Agents Chemother

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Monitoring the emergence of antibiotic resistance is a recent issue in the treatment of Legionnaires' disease. Macrolides are recommended as first-line therapy, but resistance mechanisms have not been studied in Legionella species. Our aim was to determine the molecular basis of macrolide resistance in L. pneumophila. Twelve independent lineages from a common susceptible L. pneumophila ancestral strain were propagated under conditions of erythromycin or azithromycin pressure to produce high-level macrolide resistance. Whole-genome sequencing was performed on 12 selected clones, and we investigated mutations common to all lineages. We reconstructed the dynamics of mutation for each lineage and demonstrated their involvement in decreased susceptibility to macrolides. The resistant mutants were produced in a limited number of passages to obtain a 4,096-fold increase in erythromycin MICs. Mutations affected highly conserved 5-amino-acid regions of L4 and L22 ribosomal proteins and of domain V of 23S rRNA (G2057, A2058, A2059, and C2611 nucleotides). The early mechanisms mainly affected L4 and L22 proteins and induced a 32-fold increase in the MICs of the selector drug. Additional mutations related to 23S rRNA mostly occurred later and were responsible for a major increase of macrolide MICs, depending on the mutated nucleotide, the substitution, and the number of mutated genes among the three rrl copies. The major mechanisms of the decreased susceptibility to macrolides in L. pneumophila and their dynamics were determined. The results showed that macrolide resistance could be easily selected in L. pneumophila and warrant further investigations in both clinical and environmental settings.

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Section: Discussionmentioning

confidence: 99%

“…However, treatment failures have been described and a mortality rate of over 10% is still reported in LD patients despite timely and adequate therapy (8,9). No clinical or environmental macrolide-resistant strains have been isolated so far among Legionella species, and susceptibility testing is almost never performed on Legionella strains (10).…”

mentioning

confidence: 99%

Ribosomal Mutations Conferring Macrolide Resistance in Legionella pneumophila

Descours

Ginevra

Jacotin

et al. 2017

Antimicrob Agents Chemother

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“…of azithromycin was effective in 19 cases of legionnaires disease. Tan et al [39] described a single patient with legionnaires disease and lung cancer who did not respond to azithromycin therapy.…”

Section: Discussionmentioning

confidence: 99%

Azithromycin in the Treatment of Legionella Pneumonia Requiring Hospitalization

Plouffe

Breiman

Fields

et al. 2003

Clinical Infectious Diseases

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Azithromycin is highly active against Legionella pneumophila and has been shown to be efficacious in animal models and in clinical studies of patients with legionnaires disease. This open, prospective, multicenter trial evaluated azithromycin for the treatment of legionnaires disease. Twenty-five hospitalized patients with community-acquired pneumonia and a positive result of a L. pneumophila serogroup 1 urinary antigen assay received monotherapy with intravenous azithromycin (500 mg/day) for 2-7 days, followed by oral azithromycin (1500 mg administered over the course of 3 or 5 days). The mean total duration of intravenous plus oral therapy was 7.92 days. The overall cure rate among clinically evaluable patients was 95% (20 of 21 patients) at 10-14 days after therapy and 96% (22 of 23 patients) at 4-6 weeks after therapy. The results of this study support previously reported data demonstrating that azithromycin is both safe and efficacious for the treatment of hospitalized patients with legionnaires disease.

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“…Por otro lado, un estudio efectuado en Johns Hopkins Hospital durante el año 1991, demostró que la mortalidad entre 29 pacientes con NAC y la evidencia de bacterias "atípicas" fue virtualmente cero, aun cuando solamente cuatro de estos pacientes recibieron antimicrobianos activos contra estos patógenos (es decir macrólidos o tetraciclinas) 134 . Además, no se informó una frecuencia signifi cativa de Legionella spp, un potencial patógeno fatal [172][173] en América del Sur 14,16,[44][45][46] . Por lo tanto, el grupo de consenso considera que la cobertura inicial de bacterias "atípicas" es innecesaria y baja relación costo/efectividad, en pacientes pertenecientes al Grupo 2.…”

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Neumonía aguda adquirida en la comunidad en adultos: Actualización de los lineamientos para el tratamiento antimicrobiano inicial basado en la evidencia local del Grupo de Trabajo de Sudamérica (ConsenSur II)

Bantar¹,

Curcio

Jasovich³

et al. 2010

Rev. chil. infectol.

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Community-acquired pneumonia (CAP) in adults is probably one of the infections affecting ambulatory patients for which the highest diversity of guidelines has been written worldwide. Most of them agree in that antimicrobial therapy should be initially tailored according to either the severity of the infection or the presence of comorbidities and the etiologic pathogen. Nevertheless, a great variability may be noted among the different countries in the selection of the primary choice in the antimicrobial agents, even for the cases considered as at a low-risk class. This fact may be due to the many microbial causes of CAP and specialties involved, as well as the different health-care systems effecting on the availability or cost of antibiotics. However, many countries or regions adopt some of the guidelines or design their own recommendations regardless of the local data, probably because of the scarcity of such data. This is the reason why we have developed a guideline for the initial treatment of CAP by 2002 upon the basis of several local evidences in South America (ConsenSur I). However, several issues deserve to be currently rediscussed as follows: certain clinical scores other than the Physiological Severity Index (PSI) have become more popular in clinical practice (i.e. CURB-65, CRB-65); some pathogens have emerged in the region, such as community-acquired methicillin resistant Staphylococcus aureus (CA-MRSA) and Legionella spp; new evidences on the performance of the rapid test for the etiologic diagnosis in CAP have been reported (eg. urinary Legionella and pneumococcus antigens); new therapeutic considerations needs to be approached (i.e. dosage reformulation, duration of treatment, emergence of novel antibiotics and clinical impact of combined therapy). Like in the fi rst version of the ConsenSur (ConsenSur I), the various current guidelines have helped to organize and stratify the present proposal, ConsenSur II.

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Persistently Positive Culture Results in a Patient with Community-Acquired Pneumonia Due to Legionella pneumophila

Cited by 18 publications

References 23 publications

Ribosomal Mutations Conferring Macrolide Resistance in Legionella pneumophila

Ribosomal Mutations Conferring Macrolide Resistance in Legionella pneumophila

Azithromycin in the Treatment of Legionella Pneumonia Requiring Hospitalization

Neumonía aguda adquirida en la comunidad en adultos: Actualización de los lineamientos para el tratamiento antimicrobiano inicial basado en la evidencia local del Grupo de Trabajo de Sudamérica (ConsenSur II)

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