#Neisseria meningitidis isolated from #patients in #MSMs (Rev Argent Microbiol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Rev Argent Microbiol. 2019 Oct 15. pii: S0325-7541(19)30079-3. doi: 10.1016/j.ram.2019.03.009. [Epub ahead of print]

[Neisseria meningitidis isolated from patients in men who have sex with men].

[Article in Spanish]

García SD1, Sorhuet-Pereira C2, Perazzi BE3, Losada ME3, Cabellos Astorga G3, Casco RH4, Vay CA3, Mollerach ME5, Famiglietti ÁMR3.

Author information: 1 Cátedra de Microbiología Clínica, Departamento de Bioquímica Clínica, Facultad de Farmacia y Bioquímica, Hospital de Clínicas José de San Martín, Universidad de Buenos Aires, Ciudad de Buenos Aires, Argentina. Electronic address: biosgarcia@yahoo.com.ar. 2 Cátedra de Microbiología, Departamento de Microbiología, Inmunología y Genética, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Ciudad de Buenos Aires, Argentina. 3 Cátedra de Microbiología Clínica, Departamento de Bioquímica Clínica, Facultad de Farmacia y Bioquímica, Hospital de Clínicas José de San Martín, Universidad de Buenos Aires, Ciudad de Buenos Aires, Argentina. 4 Programa de ETS, Hospital de Clínicas, Universidad de Buenos Aires, Ciudad de Buenos Aires, Argentina. 5 Cátedra de Microbiología, Departamento de Microbiología, Inmunología y Genética, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Ciudad de Buenos Aires, Argentina; CONICET, Buenos Aires, Argentina.

 

Abstract

During the periods 2000-2004 and 2014-2015, Neisseria meningitidis was investigated in men who have sex with men, 1143 and 544 respectively, who consulted in the sexually-transmitted disease program. Prevalence, serogroup distribution and susceptibility to antibiotics were determined. Pharyngeal, rectal and urethral swabs were cultivated on selective Thayer-Martin modified medium. The identification was performed by biochemical tests and mass spectrometry by MALDI-TOF. Serogroups B, C, W and Y were investigated by PCR in 85 isolates recovered from the pharynx belonging to the second period. MICs of penicillin, ceftriaxone, rifampicin, azithromycin and ciprofloxacin were determined for 66 and 102 isolates from periods 1 and 2 respectively, according to CLSI. The prevalence of N. meningitidis was 17.8% and 28.1%, in periods 1 and 2 respectively; the isolates were mainly recovered from the pharynx. The distribution of serogroups was B 31.5%; Y 7.6%; W 3.3% and 9.8% non-capsulated and the rest would belong to other serogroups. Isolates classified as intermediate to penicillin were 34.8% and 63.7% (first and second periods, respectively); moreover, 11.8% of the isolates from the second period were resistant. All isolates were susceptible to ceftriaxone, to ciprofloxacin (except 3 isolates with MIC values between 0.25 and 0.5μg/ml), 3% were resistant to rifampicin and 2% were not susceptible to azithromicin. The prevalence of N. meningitidis carriage in men who have sex with men was high with a high rate of penicillin non-susceptible isolates. B was the prevalent serogroup.

Copyright © 2019 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

KEYWORDS: Neisseria meningitidis; Resistance; Resistencia; Serogroup; Serogrupo

PMID: 31628000 DOI: 10.1016/j.ram.2019.03.009

Keywords: Antibiotics; Drugs Resistance; Penicillin; Neisseria meningitidis; Argentina.

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#Azithromycin Protects against #Zika virus #Infection by Upregulating virus-induced Type I and III #Interferon Responses (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Azithromycin Protects against Zika virus Infection by Upregulating virus-induced Type I and III Interferon Responses

Chunfeng Li, Shulong Zu, Yong-Qiang Deng, Dapei Li, Kislay Parvatiyar, Natalie Quanquin, Jingzhe Shang, Nina Sun, Jiaqi Su, Zhenyang Liu, Min Wang, Saba R. Aliyari, Xiao-Feng Li, Aiping Wu, Feng Ma, Yi Shi, Karin Nielsevn-Saines, Jae U. Jung, Frank Xiao-Feng Qin, Cheng-Feng Qin, Genhong Cheng

DOI: 10.1128/AAC.00394-19

 

ABSTRACT

Azithromycin (AZM) is a widely used antibiotic, with additional antiviral and anti-inflammatory properties that remain poorly understood. Although Zika virus (ZIKV) poses a significant threat to global health, there are currently no vaccines or effective therapeutics against it. Herein, we report that AZM effectively suppresses ZIKV infection in vitro by targeting a late stage in the viral life cycle. Besides that, AZM upregulates the expression of host type I and III interferons and several of their downstream interferon-stimulated genes (ISGs) in response to ZIKV infection. In particular, we found that AZM upregulates the expression of MDA5 and RIG-I, pathogen recognition receptors (PRRs) induced by ZIKV infection, and increases the levels of phosphorylated TBK1 and IRF3. Interestingly, AZM treatment upregulates phosphorylation of TBK1, without inducing phosphorylation of IRF3 by itself. These findings highlight the potential use of AZM as a broad antiviral agent to combat viral infection and prevent ZIKV associated devastating clinical outcomes, such as congenital microcephaly.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Antivirals; Antibiotics; Azithromycin; Zika Virus.

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#Genomic #investigation of #Staphylococcus aureus recovered from #Gambian #women and #newborns following an oral dose of intra-partum #azithromycin (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

Genomic investigation of Staphylococcus aureus recovered from Gambian women and newborns following an oral dose of intra-partum azithromycin

Abdoulie Bojang, Sarah L Baines, Liam Donovan, Romain Guerillot, Kerrie Stevens,Charlie Higgs, Christian Bottomley, Ousman Secka, Mark B Schultz,Anders Gonçalves da Silva, Torsten Seemann, Timothy P Stinear, Anna Roca,Benjamin P Howden

Journal of Antimicrobial Chemotherapy, dkz341, https://doi.org/10.1093/jac/dkz341

Published: 19 August 2019

 

Abstract

Background

Oral azithromycin given during labour reduces carriage of bacteria responsible for neonatal sepsis, including Staphylococcus aureus. However, there is concern that this may promote drug resistance.

Objectives

Here, we combine genomic and epidemiological data on S. aureus isolated from mothers and babies in a randomized intra-partum azithromycin trial (PregnAnZI) to describe bacterial population dynamics and resistance mechanisms.

Methods

Participants from both arms of the trial, who carried S. aureus in day 3 and day 28 samples post-intervention, were included. Sixty-six S. aureus isolates (from 7 mothers and 10 babies) underwent comparative genome analyses and the data were then combined with epidemiological data. Trial registration (main trial): ClinicalTrials.gov Identifier NCT01800942.

Results

Seven S. aureus STs were identified, with ST5 dominant (n = 40, 61.0%), followed by ST15 (n = 11, 17.0%). ST5 predominated in the placebo arm (73.0% versus 49.0%, P = 0.039) and ST15 in the azithromycin arm (27.0% versus 6.0%, P = 0.022). In azithromycin-resistant isolates, msr(A) was the main macrolide resistance gene (n = 36, 80%). Ten study participants, from both trial arms, acquired azithromycin-resistant S. aureus after initially harbouring a susceptible isolate. In nine (90%) of these cases, the acquired clone was an msr(A)-containing ST5 S. aureus. Long-read sequencing demonstrated that in ST5, msr(A) was found on an MDR plasmid.

Conclusions

Our data reveal in this Gambian population the presence of a dominant clone of S. aureus harbouring plasmid-encoded azithromycin resistance, which was acquired by participants in both arms of the study. Understanding these resistance dynamics is crucial to defining the public health drug resistance impacts of azithromycin prophylaxis given during labour in Africa.

Issue Section: ORIGINAL RESEARCH

Keywords: Antibiotics; Drugs Resistance; Macrolides; Azithromycin; Pregnancy; Gambia.

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Combination of #Azithromycin and #Gentamicin for Efficient #Treatment of #Pseudomonas aeruginosa Infections (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page. (LINK). Abstract, edited.]

Combination of Azithromycin and Gentamicin for Efficient Treatment of Pseudomonas aeruginosa Infections

Huan Ren, Yiwei Liu, Jingyi Zhou, Yuqing Long, Chang Liu, Bin Xia, Jing Shi, Zheng Fan,Yuying Liang, Shuiping Chen, Jun Xu, Penghua Wang, Yanhong Zhang, Guangbo Zhu,Huimin Liu, Yongxin Jin, Fang Bai, Zhihui Cheng, Shouguang Jin, Weihui Wu

The Journal of Infectious Diseases, jiz341, https://doi.org/10.1093/infdis/jiz341

Published: 16 August 2019

 

Abstract

Background

Trans-translation is a ribosome rescue system that plays an important role in bacterial tolerance to environmental stresses. It is absent in animals, making it a potential treatment target. However, its role in antibiotic tolerance in Pseudomonas aeruginosa remains unknown.

Methods

The role and activity of trans-translation during antibiotic treatment were examined with a trans-translation–deficient strain and a genetically modified trans-translation component gene, respectively. In vitro assays and murine infection models were used to examine the effects of suppression of trans-translation.

Results

We found that the trans-translation system plays an essential role in P. aeruginosa tolerance to azithromycin and multiple aminoglycoside antibiotics. We further demonstrated that gentamicin could suppress the azithromycin-induced activation of trans-translation. Compared with each antibiotic individually, gentamicin and azithromycin combined increased the killing efficacy against planktonic and biofilm-associated P. aeruginosa cells, including a reference strain PA14 and its isogenic carbapenem-resistance oprD mutant, the mucoid strain FRD1, and multiple clinical isolates. Furthermore, the gentamicin-azithromycin resulted in improved bacterial clearance in murine acute pneumonia, biofilm implant, and cutaneous abscess infection models.

Conclusions

Combination treatment with gentamicin and azithromycin is a promising strategy in combating P. aeruginosa infections.

Pseudomonas aeruginosa, trans-translation, azithromycin, antibiotic combination

Topic: antibiotics – pseudomonas aeruginosa – gentamicin sulfate (usp) – azithromycin – biofilms – gentamicins – infection – killing

Issue Section: Major Article

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Antibiotics; Drugs Resistance; Aminoglycosides; Gentamicin; Azithromycin; Pseudomonas aeruginosa; Biofilm.

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#Antibiotic #resistance and #azithromycin resistance mechanism of #Legionella pneumophila serogroup 1 in #China (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Antibiotic resistance and azithromycin resistance mechanism of Legionella pneumophila serogroup 1 in China

Xueyang Jia, Hongyu Ren, Xudong Nie, Yinan Li, Jianguo Li, Tian Qin

DOI: 10.1128/AAC.00768-19

 

ABSTRACT

Legionnaires’ disease, caused by Legionella pneumophila (Lp), was primarily treated with antibiotics. However, few reports have been published on antibiotic-resistant Legionella in China. Our aim was to determine the azithromycin resistance mechanism of Lp serogroup 1 in China. The sensitivities of 149 Lp1 strains, isolated from clinical cases or environmental water in China from 2005 to 2012, to five antibiotics including erythromycin, azithromycin, levofloxacin, moxifloxacin and rifampicin were evaluated. The mechanisms of the resistance of Lp1 to azithromycin were studied. The expression levels of efflux pump gene lpeAB and the minimum inhibitory concentration (MIC) of azithromycin-resistant strains in the presence and absence of the efflux pump inhibitor carbonyl cyanide-chlorophenylhydrazone (CCCP) were detected. All 149 strains were sensitive to erythromycin, levofloxacin, moxifloxacin and rifampicin, among which 25 strains exhibited azithromycin resistance. These 25 strains, including strains sequence type 1 (ST1), ST144, ST150, ST154 and ST629, were screened. The expression of lpeAB was responsible for the reduced azithromycin susceptibility in all these 25 strains. The phenotype of 25 strains with virulence were linked by evaluating the intracellular growth ability in mouse macrophage J774 cells. 60 % of 25 strains were more virulent than the reference strain ATCC 33152. The results in our study provide data support for the further study of antibiotic sensitivity of Lp strains in China.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Drugs Resistance; Legionella pneumophila; Azithromycin.

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#Azithromycin, a 15-membered #macrolide #antibiotic, inhibits #influenza A #H1N1pdm09 virus #infection by interfering with virus internalization process (J Antibit (Tokyo), abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

J Antibiot (Tokyo). 2019 Jul 12. doi: 10.1038/s41429-019-0204-x. [Epub ahead of print]

Azithromycin, a 15-membered macrolide antibiotic, inhibits influenza A(H1N1)pdm09 virus infection by interfering with virus internalization process.

Tran DH1,2, Sugamata R1,2,3, Hirose T4, Suzuki S1,2,3, Noguchi Y4, Sugawara A4,5, Ito F2, Yamamoto T2, Kawachi S2,3, Akagawa KS4, Ōmura S4, Sunazuka T4, Ito N6, Mimaki M6, Suzuki K7,8,9.

Author information: 1 Department of Health Protection, Graduate School of Medicine, Teikyo University, Kaga 2-11-1, Itabashi-ku, Tokyo, 173-8605, Japan. 2 Asia International Institute of Infectious Disease Control (ADC), Teikyo University, Kaga 2-11-1, Itabashi-ku, Tokyo, 173-8605, Japan. 3 General Medical Education and Research Center (G-MEC), Teikyo University, Kaga 2-11-1, Itabashi-ku, Tokyo, 173-8605, Japan. 4 Kitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, Kitasato University, Shirokane 5-9-1, Minato-ku, Tokyo, 108-8641, Japan. 5 Graduate School of Pharmaceutical Sciences, Tohoku University, Aza-Aoba 6-3, Aramaki, Aoba-ku, Sendai, 980-8578, Japan. 6 The Pediatric Department, Teikyo Hospital University, Kaga 2-11-1, Itabashi-ku, Tokyo, 173-8605, Japan. 7 Department of Health Protection, Graduate School of Medicine, Teikyo University, Kaga 2-11-1, Itabashi-ku, Tokyo, 173-8605, Japan. suzuki-k@med.teikyo-u.ac.jp. 8 Asia International Institute of Infectious Disease Control (ADC), Teikyo University, Kaga 2-11-1, Itabashi-ku, Tokyo, 173-8605, Japan. suzuki-k@med.teikyo-u.ac.jp. 9 General Medical Education and Research Center (G-MEC), Teikyo University, Kaga 2-11-1, Itabashi-ku, Tokyo, 173-8605, Japan. suzuki-k@med.teikyo-u.ac.jp.

 

Abstract

The pandemic influenza 2009 (A(H1N1)pdm09) virus currently causes seasonal and annual epidemic outbreaks. The widespread use of anti-influenza drugs such as neuraminidase and matrix protein 2 (M2) channel inhibitors has resulted in the emergence of drug-resistant influenza viruses. In this study, we aimed to determine the anti-influenza A(H1N1)pdm09 virus activity of azithromycin, a re-positioned macrolide antibiotic with potential as a new anti-influenza candidate, and to elucidate its underlying mechanisms of action. We performed in vitro and in vivo studies to address this. Our in vitro approaches indicated that progeny virus replication was remarkably inhibited by treating viruses with azithromycin before infection; however, azithromycin administration after infection did not affect this process. We next investigated the steps inhibited by azithromycin during virus invasion. Azithromycin did not affect attachment of viruses onto the cell surface, but blocked internalization into host cells during the early phase of infection. We further demonstrated that azithromycin targeted newly budded progeny virus from the host cells and inactivated their endocytic activity. This unique inhibitory mechanism has not been observed for other anti-influenza drugs, indicating the potential activity of azithromycin before and after influenza virus infection. Considering these in vitro observations, we administered azithromycin intranasally to mice infected with A(H1N1)pdm09 virus. Single intranasal azithromycin treatment successfully reduced viral load in the lungs and relieved hypothermia, which was induced by infection. Our findings indicate the possibility that azithromycin could be an effective macrolide for the treatment of human influenza.

PMID:  31300721  DOI: 10.1038/s41429-019-0204-x

Keywords: Antibiotics; Azithromycin; Influenza A; H1N1pdm09.

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#Gentamicin compared with #ceftriaxone for the #treatment of #gonorrhoea (G-ToG): a randomised non-inferiority trial (Lancet, abstract)

[Source: The Lancet, full page: (LINK). Abstract, edited.]

Gentamicin compared with ceftriaxone for the treatment of gonorrhoea (G-ToG): a randomised non-inferiority trial

Prof Jonathan D C Ross, MD, Clare Brittain, BMedSc, Michelle Cole, DBMS, Claire Dewsnap, MD, Jan Harding, PhD, Trish Hepburn, BSc, Louise Jackson, PhD, Matthew Keogh, Tessa Lawrence, PhD, Prof Alan A Montgomery, PhD, Prof Tracy E Roberts, PhD, Kirsty Sprange, MSc, Wei Tan, MSc, Sukhwinder Thandi, PhD, John White, FRCP, Janet Wilson, FRCP, Prof Lelia Duley, MD, on behalf of theG-ToG trial team

Published: May 02, 2019 / DOI: https://doi.org/10.1016/S0140-6736(18)32817-4

 

Summary

Background

Gonorrhoea is a common sexually transmitted infection for which ceftriaxone is the current first-line treatment, but antimicrobial resistance is emerging. The objective of this study was to assess the effectiveness of gentamicin as an alternative to ceftriaxone (both combined with azithromycin) for treatment of gonorrhoea.

Methods

G-ToG was a multicentre, parallel-group, pragmatic, randomised, non-inferiority trial comparing treatment with gentamicin to treatment with ceftriaxone for patients with gonorrhoea. The patients, treating physician, and assessing physician were masked to treatment but the treating nurse was not. The trial took place at 14 sexual health clinics in England. Adults aged 16–70 years were eligible for participation if they had a diagnosis of uncomplicated genital, pharyngeal, or rectal gonorrhoea. Participants were randomly assigned to receive a single intramuscular dose of either gentamicin 240 mg (gentamicin group) or ceftriaxone 500 mg (ceftriaxone group). All participants also received a single 1 g dose of oral azithromycin. Randomisation (1:1) was stratified by clinic and performed using a secure web-based system. The primary outcome was clearance of Neisseria gonorrhoeae at all initially infected sites, defined as a negative nucleic acid amplification test 2 weeks post treatment. Primary outcome analyses included only participants who had follow-up data, irrespective of the baseline visit N gonorrhoeae test result. The margin used to establish non-inferiority was a lower confidence limit of 5% for the risk difference. This trial is registered with ISRCTN, number ISRCTN51783227.

Findings

Of 1762 patients assessed, we enrolled 720 participants between Oct 7, 2014, and Nov 14, 2016, and randomly assigned 358 to gentamicin and 362 to ceftriaxone. Primary outcome data were available for 306 (85%) of 362 participants allocated to ceftriaxone and 292 (82%) of 358 participants allocated to gentamicin. At 2 weeks after treatment, infection had cleared for 299 (98%) of 306 participants in the ceftriaxone group compared with 267 (91%) of 292 participants in the gentamicin group (adjusted risk difference −6·4%, 95% CI −10·4% to −2·4%). Of the 328 participants who had a genital infection, 151 (98%) of 154 in the ceftriaxone group and 163 (94%) of 174 in the gentamicin group had clearance at follow-up (adjusted risk difference −4·4%, −8·7 to 0). For participants with a pharyngeal infection, a greater proportion receiving ceftriaxone had clearance at follow-up (108 [96%] in the ceftriaxone group compared with 82 [80%] in the gentamicin group; adjusted risk difference −15·3%, −24·0 to −6·5). Similarly, a greater proportion of participants with rectal infection in the ceftriaxone group had clearance (134 [98%] in the ceftriaxone group compared with 107 [90%] in the gentamicin group; adjusted risk difference −7·8%, −13·6 to −2·0). Thus, we did not find that a single dose of gentamicin 240 mg was non-inferior to a single dose of ceftriaxone 500 mg for the treatment of gonorrhoea, when both drugs were combined with a 1 g dose of oral azithromycin. The side-effect profiles were similar between groups, although severity of pain at the injection site was higher for gentamicin (mean visual analogue pain score 36 of 100 in the gentamicin group vs 21 of 100 in the ceftriaxone group).

Interpretation

Gentamicin is not appropriate as first-line treatment for gonorrhoea but remains potentially useful for patients with isolated genital infection, or for patients who are allergic or intolerant to ceftriaxone, or harbour a ceftriaxone-resistant isolate. Further research is required to identify and test new alternatives to ceftriaxone for the treatment of gonorrhoea.

Funding

UK National Institute for Health Research.

Keywords: Antibiotics; Drugs Resistance; Neisseria gonorrhoeae; Ceftriaxone; Azithromycin; Gentamicin.

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