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1.
Emerg Infect Dis ; 30(7): 1475-1477, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38916800

RESUMO

Pasteurella bettyae is a gram-negative bacillus sporadically involved in human infections; its main reservoirs are cats and dogs. A recent publication suggests the possibility of sexual transmission leading to genital infections in men who have sex with men. We report 9 cases in France of genital infection among this population.


Assuntos
Homossexualidade Masculina , Infecções por Pasteurella , Pasteurella , Humanos , Masculino , França/epidemiologia , Adulto , Infecções por Pasteurella/transmissão , Infecções por Pasteurella/microbiologia , Pasteurella/isolamento & purificação , Pasteurella/genética , Pasteurella/classificação , Pessoa de Meia-Idade , Adulto Jovem
2.
J Antimicrob Chemother ; 79(3): 539-545, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38197448

RESUMO

OBJECTIVES: Haemophilus parainfluenzae is an opportunistic pathogen causing respiratory tract infection and sexually transmitted diseases. The emergence of multidrug resistance in this species is particularly worrisome, especially since the recent description of CTX-M-15 ESBL-producing isolates in Spain. The aim of this study was to characterize a CTX-M-15-producing H. parainfluenzae clinical isolate, HP01, obtained from a urethral swab. METHODS: MICs were determined with gradient strips for this isolate. Hydrolysis assays were performed with the ß LACTA test. Genomic DNA from HP01 was subjected to Illumina and Oxford Nanopore sequencing to investigate the genetic environment of blaCTX-M-15. Phylogenetic analysis was performed with available H. parainfluenzae genomes from the NCBI database, including CTX-M-15 producers. RESULTS: HP01, an XDR isolate, was resistant to penicillin, third-generation cephalosporins, fluoroquinolones, macrolides, cyclines and co-trimoxazole and susceptible only to carbapenems and rifampicin. HP01 carried blaTEM-1, blaCTX-M-15, tet(M), catS and mef(E)/mel and harboured amino acid substitutions in PBP3, PBP5, GyrA, ParC and FolA implicated in resistance. Genomic analysis revealed that blaCTX-M-15 was carried by a Tn3-like transposon inserted into a novel integrative and conjugative element (ICE), ICEHpaSLS, present on the chromosome and belonging to the ICEHin1056 family described in Haemophilus influenzae. The tet(M)-MEGA element was also detected on the chromosome. No plasmid was found. The phylogenetic analysis showed that four H. parainfluenzae producing CTX-M-15 clustered in the same clade. CONCLUSIONS: Here we report the description of an XDR H. parainfluenzae producing blaCTX-M-15 isolated from a urethral swab. The blaCTX-M-15 gene was inserted into an ICE structure similar to those recently described in CTX-M-15 producers in Spain. The emergence of XDR H. parainfluenzae producing blaCTX-M-15 is a matter of great concern. Careful surveillance is required to prevent its spread.


Assuntos
Antibacterianos , Haemophilus parainfluenzae , Haemophilus parainfluenzae/genética , Filogenia , Antibacterianos/farmacologia , Substituição de Aminoácidos , beta-Lactamases/genética
3.
Eur J Clin Microbiol Infect Dis ; 43(5): 1025-1029, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38472519

RESUMO

The diagnosis of long COVID often relies on symptoms post-COVID-19, occasionally lacking biological evidence. This case study illustrates how investigating long COVID uncovered an underlying bartonellosis through clinical metagenomics. Following mild COVID-19, a 26-year-old woman experienced persistent symptoms during 5 months, including axillary adenopathy. Pathological examination, 16 S rRNA PCR, and clinical metagenomic analysis were done on an adenopathy biopsy. The latter revealed Bartonella henselae DNA and RNA. Treatment with clarithromycin improved symptoms. This case underscores the relevance of clinical metagenomics in diagnosing hidden infections. Post-COVID symptoms warrant thorough investigation, and bartonellosis should be considered in polyadenopathy cases, regardless of a recent history of cat or flea exposures.


Assuntos
Bartonella henselae , COVID-19 , Metagenômica , Humanos , Feminino , Bartonella henselae/genética , Bartonella henselae/isolamento & purificação , Adulto , COVID-19/diagnóstico , COVID-19/complicações , Metagenômica/métodos , SARS-CoV-2/genética , Antibacterianos/uso terapêutico , Claritromicina/uso terapêutico
4.
Artigo em Inglês | MEDLINE | ID: mdl-38676856

RESUMO

We present our findings on interpatient transmission, epidemic control measures, and the outcomes of a series of ten critically ill burn patients who were either colonized or infected with carbapenem-resistant Acinetobacter baumannii (CRAB). None of the five infected patients achieved clinical cure, and all experienced relapses. Microbiological failure was observed in 40% of the infected patients. The isolated CRAB strains were found to carry blaOXA-23 and armA resistance genes. Despite the lack of clinical cure, all five infected patients survived and were discharged from the Burn Intensive Care Unit.

5.
Clin Infect Dis ; 76(12): 2154-2162, 2023 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-36785526

RESUMO

BACKGROUND: The optimal duration of antimicrobial therapy for urinary tract infections (UTIs) in men remains controversial. METHODS: To compare 7 days to 14 days of total antibiotic treatment for febrile UTIs in men, this multicenter randomized, double-blind. placebo-controlled noninferiority trial enrolled 282 men from 27 centers in France. Men were eligible if they had a febrile UTI and urine culture showing a single uropathogen. Participants were treated with ofloxacin or a third-generation cephalosporin at day 1, then randomized at day 3-4 to either continue ofloxacin for 14 days total treatment, or for 7 days followed by placebo until day 14. The primary endpoint was treatment success, defined as a negative urine culture and the absence of fever and of subsequent antibiotic treatment between the end of treatment and 6 weeks after day 1. Secondary endpoints included recurrent UTI within weeks 6 and 12 after day 1, rectal carriage of antimicrobial-resistant Enterobacterales, and drug-related events. RESULTS: Two hundred forty participants were randomly assigned to receive antibiotic therapy for 7 days (115 participants) or 14 days (125 participants). In the intention-to-treat analysis, treatment success occurred in 64 participants (55.7%) in the 7-day group and in 97 participants (77.6%) in the 14-day group (risk difference, -21.9 [95% confidence interval, -33.3 to -10.1]), demonstrating inferiority. Adverse events during antibiotic therapy were reported in 4 participants in the 7-day arm and 7 in the 14-day arm. Rectal carriage of resistant Enterobacterales did not differ between both groups. CONCLUSIONS: A treatment with ofloxacin for 7 days was inferior to 14 days for febrile UTI in men and should therefore not be recommended. CLINICAL TRIALS REGISTRATION: NCT02424461; Eudra-CT: 2013-001647-32.


Assuntos
Anti-Infecciosos , Infecções Urinárias , Masculino , Humanos , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/complicações , Antibacterianos/efeitos adversos , Anti-Infecciosos/uso terapêutico , Febre/tratamento farmacológico , Febre/complicações , Método Duplo-Cego , Ofloxacino/uso terapêutico
6.
J Antimicrob Chemother ; 78(8): 1982-1991, 2023 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-37352017

RESUMO

OBJECTIVES: Global antimicrobial resistance (AMR) surveillance in Neisseria gonorrhoeae is essential. In 2017-18, only five (10.6%) countries in the WHO African Region reported to the WHO Global Gonococcal Antimicrobial Surveillance Programme (WHO GASP). Genomics enhances our understanding of gonococcal populations nationally and internationally, including AMR strain transmission; however, genomic studies from Africa are extremely scarce. We describe the gonococcal genomic lineages/sublineages, including AMR determinants, and baseline genomic diversity among strains in Uganda, Malawi and South Africa, 2015-20, and compare with sequences from Kenya and Burkina Faso. METHODS: Gonococcal isolates cultured in Uganda (n = 433), Malawi (n = 154) and South Africa (n = 99) in 2015-20 were genome-sequenced. MICs were determined using ETEST. Sequences of isolates from Kenya (n = 159), Burkina Faso (n = 52) and the 2016 WHO reference strains (n = 14) were included in the analysis. RESULTS: Resistance to ciprofloxacin was high in all countries (57.1%-100%). All isolates were susceptible to ceftriaxone, cefixime and spectinomycin, and 99.9% were susceptible to azithromycin. AMR determinants for ciprofloxacin, benzylpenicillin and tetracycline were common, but rare for cephalosporins and azithromycin. Most isolates belonged to the more antimicrobial-susceptible lineage B (n = 780) compared with the AMR lineage A (n = 141), and limited geographical phylogenomic signal was observed. CONCLUSIONS: We report the first multi-country gonococcal genomic comparison from Africa, which will support the WHO GASP and WHO enhanced GASP (EGASP). The high prevalence of resistance to ciprofloxacin (and empirical use continues), tetracycline and benzylpenicillin, and the emerging resistance determinants for azithromycin show it is imperative to strengthen the gonococcal AMR surveillance, ideally including genomics, in African countries.


Assuntos
Antibacterianos , Gonorreia , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Neisseria gonorrhoeae , Azitromicina/farmacologia , Malaui , África do Sul , Uganda/epidemiologia , Farmacorresistência Bacteriana , Gonorreia/epidemiologia , Gonorreia/tratamento farmacológico , Ciprofloxacina/farmacologia , Testes de Sensibilidade Microbiana , Tetraciclina/farmacologia , Genômica
7.
J Med Virol ; 95(9): e29068, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37654019

RESUMO

Men who have sex with men (MSM) are at high risk of sexually transmitted infections, among which HPV infections are particularly prominent. We took advantage of the MémoDépistages study to evaluate HPV distribution at anal and oropharyngeal sites in HIV-negative multipartner MSM. HPV DNA was detected in 82% (n = 344) of anal and 11% (n = 45) of oropharyngeal self-collected samples taken from 421 participants. Multiple HPV types were detected in 70% of anal samples, and single HPV types in 91% of oropharyngeal samples. HPV16 was the most frequent type detected in the anus, followed by HPV6, HPV51, and HPV52. HPV6, HPV16, and HPV11 were the most prevalent types in the oropharynx. HPV targeted by the nonavalent vaccine was detected in 71% and 50% of HPV-positive anal and oropharyngeal samples, respectively. The main risk factor associated with HPV detection was frequenting gay meeting places, living in large cities, and having an anal Chlamydia trachomatis/Neisseria gonorrhoeae infection. In this cohort of highly sexually active MSM, HPV detection was highly frequent and rendered them at high risk of precancerous and cancerous lesions. Universal vaccination against HPV before sexual debut is an important public health strategy to prevent HPV-associated cancers in this highly vulnerable population of HIV-negative MSM.


Assuntos
Doenças do Ânus , Infecções por HIV , Infecções por Papillomavirus , Minorias Sexuais e de Gênero , Masculino , Humanos , Canal Anal , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Homossexualidade Masculina , Papillomavirus Humano 16 , Papillomaviridae/genética , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia
8.
Euro Surveill ; 28(37)2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37707979

RESUMO

We report two extensively drug-resistant (XDR) Neisseria gonorrhoeae (NG) isolates combining high-level resistance to azithromycin and resistance to ceftriaxone, obtained in France from two heterosexual patients, one of whom returned from Cambodia. Whole genome sequencing identified MLST ST16406, the mosaic penA-60.001 which caused ceftriaxone resistance in the internationally spreading FC428 clone, and the A2059G mutation in the 23S rRNA gene. The NG isolates F93 and F94 were related to XDR isolates detected in Austria and the United Kingdom in 2022.


Assuntos
Ceftriaxona , Gonorreia , Humanos , Azitromicina/farmacologia , Ceftriaxona/farmacologia , França , Gonorreia/diagnóstico , Gonorreia/tratamento farmacológico , Tipagem de Sequências Multilocus , Neisseria gonorrhoeae/genética
9.
Antimicrob Agents Chemother ; 66(9): e0044722, 2022 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-35980232

RESUMO

First variants of the Klebsiella pneumoniae carbapenemase (KPC), KPC-2 and KPC-3, have encountered a worldwide success, particularly in K. pneumoniae isolates. These beta-lactamases conferred resistance to most beta-lactams including carbapenems but remained susceptible to new beta-lactam/beta-lactamase inhibitors, such as ceftazidime-avibactam. After the marketing of ceftazidime-avibactam, numerous variants of KPC resistant to this association have been described among isolates recovered from clinical samples or derived from experimental studies. In KPC variants resistant to ceftazidime-avibactam, point mutations, insertions and/or deletions have been described in various hot spots. Deciphering the impact of these mutations is crucial, not only from a therapeutic point of view, but also to follow the evolution in time and space of KPC variants resistant to ceftazidime-avibactam. In this review, we describe the mutational landscape of the KPC beta-lactamase toward ceftazidime-avibactam resistance based on a multidisciplinary approach including epidemiology, microbiology, enzymology, and thermodynamics. We show that resistance is associated with three hot spots, with a high representation of insertions and deletions compared with other class A beta-lactamases. Moreover, extension of resistance to ceftazidime-avibactam is associated with a trade-off in the resistance to other beta-lactams and a decrease in enzyme stability. Nevertheless, the high natural stability of KPC could underlay the propensity of this enzyme to acquire in vivo mutations conferring resistance to ceftazidime-avibactam (CAZavi), particularly via insertions and deletions.


Assuntos
Compostos Azabicíclicos , Ceftazidima , Farmacorresistência Bacteriana Múltipla , Klebsiella pneumoniae , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Compostos Azabicíclicos/farmacologia , Compostos Azabicíclicos/uso terapêutico , Proteínas de Bactérias/genética , Carbapenêmicos/farmacologia , Ceftazidima/farmacologia , Ceftazidima/uso terapêutico , Combinação de Medicamentos , Humanos , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Inibidores de beta-Lactamases/farmacologia , beta-Lactamases/genética
10.
Antimicrob Agents Chemother ; 66(2): e0194921, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-34871091

RESUMO

We described and characterized Shiga-toxin-producing Escherichia coli (STEC) strains with high levels of resistance to azithromycin isolated in France between 2004 and 2020. Nine of 1,715 (0.52%) STEC strains were resistant to azithromycin, with an increase since 2017. One isolate carried a plasmid-borne mef(C)-mph(G) gene combination, described here for the first time for E. coli. Azithromycin resistance, although rare, needs consideration, as this treatment may be useful in cases of STEC infection.


Assuntos
Infecções por Escherichia coli , Proteínas de Escherichia coli , Escherichia coli Shiga Toxigênica , Azitromicina/farmacologia , Infecções por Escherichia coli/tratamento farmacológico , Proteínas de Escherichia coli/genética , Humanos , Plasmídeos/genética , Escherichia coli Shiga Toxigênica/genética
11.
Appl Environ Microbiol ; 88(11): e0022022, 2022 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-35575550

RESUMO

Genus Pectobacterium bacteria include important agricultural pathogens. Pectobacterium versatile isolates contain a chromosome-borne beta-lactamase, PEC-1. This enzyme is the closest relative of TEM-1, a plasmid-borne beta-lactamase widespread in the Enterobacterales. We performed bioinformatics and phenotypic analyses to investigate the genetic and phenotypic features of PEC-1 and its frequency and ability to spread within genus Pectobacterium. We also compared the characteristics of PEC-1 and TEM-1 and evaluated the likelihood of transfer. We found that blaPEC-1 was present principally in a small number of genetic environments in P. versatile. Identical blaPEC-1 genetic environments were present in closely related species, consistent with the high frequency of genetic exchange within the genus Pectobacterium. Despite the similarities between PEC-1 and TEM-1, their genetic environments displayed no significant identity, suggesting an absence of recent transfer. Phenotypic analyses on clonal constructs revealed similar hydrolysis spectra. Our results suggest that P. versatile is the main reservoir of PEC-1, which seems to transfer to closely related species. The genetic distance between PEC-1 and TEM-1, and the lack of conserved elements in their genetic environments, suggest that any transfer that may have occurred must have taken place well before the antibiotic era. IMPORTANCE This study aimed to compare the chromosomal beta-lactamase from Pectobacterium versatile, PEC-1, with the well-known and globally distributed TEM-1 in terms of genetic and functional properties. Despite the similarities between the enzymes, we obtained no definitive proof of gene transfer for the emergence of blaPEC-1 from blaTEM-1. Indeed, given the limited degree of sequence identity and the absence of a common genetic environment, it seems unlikely that any transfer of this gene has occurred recently. However, although blaPEC-1 was found mostly in one specific clade of the P. versatile species, certain isolates from other closely related species, such as Pectobacterium brasiliense and Pectobacterium polaris, may also carry this gene inserted into common genetic environments. This observation suggests that genetic exchanges are frequent, accounting for the diffusion of blaPEC-1 between isolates from different Pectobacterium species and, potentially, to exogenous mobile genetic elements.


Assuntos
Pectobacterium , beta-Lactamases , Antibacterianos , Pectobacterium/genética , Plasmídeos/genética , beta-Lactamases/genética
12.
Eur J Clin Microbiol Infect Dis ; 41(10): 1269-1273, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36001207

RESUMO

A 45-year-old female patient receiving rituximab for B cell non-Hodgkin follicular lymphoma presented unexplained recurrent fever, abdominal discomfort, and pollakiuria. We performed shotgun metagenomic sequencing from peri-kidney collection that identified a co-infection with Mycoplasma hominis and Ureaplasma urealyticum. The patient recovered with sequelae after appropriate antibiotic treatment was given.


Assuntos
Infecções por Mycoplasma , Infecções por Ureaplasma , Antibacterianos/uso terapêutico , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Pessoa de Meia-Idade , Infecções por Mycoplasma/microbiologia , Mycoplasma hominis , Rituximab/uso terapêutico , Ureaplasma , Infecções por Ureaplasma/microbiologia , Ureaplasma urealyticum
13.
Bioorg Med Chem Lett ; 55: 128450, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34774742

RESUMO

This paper reports on the design of a series of 10 novel lipophilic piperazinyl derivatives of the 1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, their synthesis, their characterisation by 1H, 13C and 19F NMR, IR spectroscopy and HRMS, as well as their biological activity against bacteria of medical interest. Among these derivatives, 2 were as potent as the parent quinolone against Neisseriagonorrhoeae whereas all the compounds displayed lower activity than the parent quinolone against other bacteria of medical interest. Our results showing that the increased lipophilicity was deleterious for antibacterial activity may help to design new quinolone derivatives in the future, especially lipophilic quinolones which have been poorly investigated previously.


Assuntos
Antibacterianos/farmacologia , Neisseria gonorrhoeae/efeitos dos fármacos , Quinolonas/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Relação Dose-Resposta a Droga , Interações Hidrofóbicas e Hidrofílicas , Testes de Sensibilidade Microbiana , Estrutura Molecular , Quinolonas/síntese química , Quinolonas/química , Relação Estrutura-Atividade
14.
Euro Surveill ; 27(39)2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36177869

RESUMO

BackgroundDiagnoses of bacterial sexually transmitted infections (STIs) have increased in France since the 2000s. The main strategy to control STI transmission is recommending/facilitating access to condom use, testing, and antibiotic treatments.AimThis study analyses the evolution of STI testing in the private sector in France from 2006 to 2020.MethodsNational health insurance reimbursement data were used to determine numbers and rates of individuals aged ≥ 15 years tested for diagnoses of chlamydia, gonorrhoea and syphilis in the private sector in France and to describe their evolution from 2006 to 2020.ResultsUpward tendencies in testing were observed from 2006 to 2019 for all three STIs. The highest testing rates were identified in people aged 25‒29-years old. The observed testing-increase from 2017 to 2019 was twice as high in young people (< 25 years old) as in older people. In 2019, chlamydia, gonorrhoea and syphilis testing rates were respectively 45.4 (+ 21% since 2017), 41.3 (+ 60%), and 47.2 (+ 22%) per 1,000 inhabitants. For all STIs combined, the number of tested individuals decreased by 37% between March and April 2020 during the first COVID-19 epidemic wave and lockdown in France.ConclusionImprovements found in STI testing rates may have resulted from better awareness, especially among young people and health professionals, of the importance of testing, following prevention campaigns. Nevertheless, testing levels remain insufficient considering increasing diagnoses. In 2020, the COVID-19 pandemic had a considerable impact on STI testing. Partner notification and offering diverse testing opportunities including self-sampling are essential to control STI epidemics particularly in exposed populations.


Assuntos
COVID-19 , Infecções por Chlamydia , Gonorreia , Infecções por HIV , Infecções Sexualmente Transmissíveis , Sífilis , Adolescente , Adulto , Idoso , Antibacterianos , Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/epidemiologia , Infecções por Chlamydia/prevenção & controle , Controle de Doenças Transmissíveis , Atenção à Saúde , Gonorreia/diagnóstico , Gonorreia/epidemiologia , Infecções por HIV/epidemiologia , Humanos , Pandemias , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções Sexualmente Transmissíveis/prevenção & controle , Sífilis/epidemiologia
15.
Euro Surveill ; 27(50)2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36695466

RESUMO

We report a ceftriaxone-resistant, multidrug-resistant urogenital gonorrhoea case in a heterosexual woman in France, June 2022. The woman was successfully treated with azithromycin 2 g. She had unprotected sex with her regular partner, who developed urethritis following travel to Vietnam and Switzerland. Whole genome sequencing of the gonococcal isolate (F92) identified MLST ST1901, NG-STAR CC-199, and the novel mosaic penA-237.001, which caused ceftriaxone resistance. penA-237.001 is 98.7% identical to penA-60.001, reported in various ceftriaxone-resistant strains, including the internationally spreading FC428 clone.


Assuntos
Ceftriaxona , Gonorreia , Humanos , Feminino , Ceftriaxona/farmacologia , Ceftriaxona/uso terapêutico , Neisseria gonorrhoeae , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Tipagem de Sequências Multilocus , Gonorreia/diagnóstico , Gonorreia/tratamento farmacológico , Testes de Sensibilidade Microbiana , Farmacorresistência Bacteriana/genética
16.
Clin Infect Dis ; 73(7): e2127-e2133, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-33305785

RESUMO

BACKGROUND: Mycoplasma genitalium (MG) is an emerging pathogen among men who have sex with men (MSM) with raising rates of antibiotic resistance. This study assessed the prevalence and incidence of MG infection in MSM enrolled in the open-label phase of the ANRS IPERGAY trial with on-demand tenofovir disoproxil fumarate/emtricitabine for human immunodeficiency virus prevention and the impact of doxycycline post-exposure prophylaxis (PEP). METHODS: 210 subjects were tested at baseline and at 6 months by real-time PCR assays for MG detection in urine samples and oropharyngeal and anal swabs. Resistance to azithromycin (AZM), to fluoroquinolones (FQs), and to doxycycline was investigated in the French National Reference Center of Bacterial Sexually Transmitted Infections (STIs). RESULTS: The all-site prevalence of MG at baseline was 10.5% (6.3% in urine samples, 4.3% in anal swabs, 0.5% in throat swabs) and remained unchanged at 6 months whether or not PEP was used: 9.9% overall, 10.2% with PEP, 9.6% without. The overall rate of MG resistance (prevalent and incident cases) to AZM and FQs was 67.6% and 9.1%, respectively, with no difference between arms. An in vivo mutation of the MG 16S rRNA, which could be associated with tetracycline resistance, was observed in 12.5% of specimens tested. CONCLUSIONS: The prevalence of MG infection among MSM on pre-exposure prophylaxis was high and its incidence was not decreased by doxycycline prophylaxis with a similar high rate of AZM and FQ resistance, raising challenging issues for the treatment of this STI and supporting current recommendations to avoid testing or treatment of asymptomatic MG infection.


Assuntos
Infecções por HIV , Infecções por Mycoplasma , Mycoplasma genitalium , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Resistência Microbiana a Medicamentos , Infecções por HIV/epidemiologia , Homossexualidade Masculina , Humanos , Masculino , Infecções por Mycoplasma/tratamento farmacológico , Infecções por Mycoplasma/epidemiologia , Infecções por Mycoplasma/prevenção & controle , Mycoplasma genitalium/genética , Prevalência , RNA Ribossômico 16S
17.
J Antimicrob Chemother ; 76(5): 1150-1154, 2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33537731

RESUMO

OBJECTIVES: Tetracyclines are widely used for the treatment of bacterial sexually transmitted infections (STIs) and recently have been used successfully for post-exposure prophylaxis of STIs in MSM. We investigated the in vitro and in vivo development of tetracycline resistance in Chlamydia trachomatis and Mycoplasma genitalium and evaluated 16S rRNA mutations associated with acquired resistance in other bacteria. METHODS: In vitro selection of resistant mutants of reference strains of C. trachomatis and M. genitalium was undertaken by serial passage in medium containing subinhibitory concentrations of tetracycline or doxycycline, respectively. The 16S rRNA gene of the two microorganisms was amplified and sequenced at different passages, as were those of 43 C. trachomatis- and 106 M. genitalium-positive specimens collected in France from 2013 to 2019. RESULTS: No tetracycline- or doxycycline-resistant strains of C. trachomatis and M. genitalium, respectively, were obtained after 30 serial passages. The tetracycline and doxycycline MICs were unchanged and analysis of the 16S rRNA gene, the molecular target of tetracyclines, of C. trachomatis and M. genitalium revealed no mutation. No mutation in the 16S rRNA gene was detected in C. trachomatis-positive specimens. However, six M. genitalium-positive specimens harboured a mutation potentially associated with tetracycline resistance without known prior tetracycline treatment for patients. CONCLUSIONS: Tetracyclines did not select in vitro-resistant mutants of C. trachomatis or M. genitalium. However, 16S rRNA mutations either responsible for or associated with tetracycline resistance in other bacteria, including mycoplasma species, were identified in several M. genitalium-positive specimens.


Assuntos
Infecções por Mycoplasma , Mycoplasma genitalium , Minorias Sexuais e de Gênero , Chlamydia trachomatis/genética , França , Homossexualidade Masculina , Humanos , Masculino , Mutação , Mycoplasma genitalium/genética , Prevalência , RNA Ribossômico 16S/genética , Resistência a Tetraciclina/genética
18.
Antimicrob Agents Chemother ; 64(12)2020 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-33020157

RESUMO

To explore the mutational possibilities of insertions and deletions (indels) in the Klebsiella pneumoniae carbapenemase (KPC) beta-lactamase, we selected for ceftazidime-avibactam-resistant mutants. Of 96 screened mutants, we obtained 19 indels (2 to 15 amino acids), all located in the loops surrounding the active site. Three antibiotic susceptibility phenotypes emerged: an extended-spectrum-beta-lactamase-like phenotype, an activity restricted to ceftazidime, and a carbapenem-susceptible KPC-like phenotype. Tolerance for indels reflects the evolvability of KPC beta-lactamase, which could challenge the therapeutic management of patients.


Assuntos
Compostos Azabicíclicos , Ceftazidima , Infecções por Klebsiella , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Compostos Azabicíclicos/farmacologia , Proteínas de Bactérias/genética , Ceftazidima/farmacologia , Combinação de Medicamentos , Humanos , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/genética , Testes de Sensibilidade Microbiana , beta-Lactamases/genética
19.
J Clin Microbiol ; 58(11)2020 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-32878954

RESUMO

The worldwide emergence and spread of antimicrobial resistance in Gram-negative bacteria are severely limiting therapeutic options and thus constitute a major public health threat. The timely accurate detection of carbapenemase producers and the determination of carbapenemase class according to the Ambler classification can guide antimicrobial therapy and facilitate infection control measures. A modified version of the carbapenemase inactivation method (CIM), mCIM, was described and approved by the CLSI in 2017. We evaluated the performance of a faster new mCIM-based assay, mCIMplus, which can detect carbapenemase activity within 8 h and characterize the carbapenemase according to the Ambler classification in 20 h. A panel of 137 isolates producing carbapenemases (GES, IMP, KPC, NDM, OXA-48, OXA-48-like, and VIM enzymes) and 22 non-carbapenemase-producing isolates was used to evaluate the performance of mCIMplus. We evaluated the detection of carbapenemase activity at 8 and 20 h. Carbapenemase class was determined, with specific inhibitors, at 20 h. The sensitivities of mCIMplus were 99.3% at 8 h and 98.5% at 20 h. Its specificity was 100% regardless of culture time. Based on a decision algorithm, this test successfully identified the carbapenemase class for 98.4% of the tested isolates (127/129). Characterization was correct for 100, 95, and 100% of Ambler class A, B, and D isolates, respectively. This test can, therefore, be used to detect carbapenemase activity within 8 h and to determine carbapenemase class within 20 h. It constitutes a very affordable (<€1 per isolate) and reliable technique requiring only basic laboratory equipment.


Assuntos
Proteínas de Bactérias , beta-Lactamases , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Humanos , beta-Lactamases/genética
20.
J Antimicrob Chemother ; 75(7): 1726-1735, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32300786

RESUMO

BACKGROUND: The resistance to all aminoglycosides (AGs) conferred by 16S rRNA methyltransferase enzymes (16S-RMTases) is a major public health concern. OBJECTIVES: To characterize the resistance genotype, its genetic environment and plasmid support, and the phylogenetic relatedness of 16S-RMTase-producing Escherichia coli from France. METHODS: We screened 137 E. coli isolates resistant to all clinically relevant AGs from nine Parisian hospitals for 16S-RMTases. WGS was performed on clinical isolates with high-level AG resistance (MIC ≥256 mg/L) and their transformants. RESULTS: Thirty of the 137 AG-resistant E. coli produced 16S-RMTases: 11 ArmA, 18 RmtB and 1 RmtC. The 16S-RMTase producers were also resistant to third-generation cephalosporins (90% due to a blaCTX-M gene), co-trimoxazole, fluoroquinolones and carbapenems (blaNDM and blaVIM genes) in 97%, 83%, 70% and 10% of cases, respectively. Phylogenomic diversity was high in ArmA producers, with 10 different STs, but a similar genetic environment, with the Tn1548 transposon carried by a plasmid closely related to pCTX-M-3 in 6/11 isolates. Conversely, RmtB producers belonged to 12 STs, the most frequent being ST405 and ST complex (STc) 10 (four and four isolates, respectively). The rmtB gene was carried by IncF plasmids in 10 isolates and was found in different genetic environments. The rmtC gene was carried by the pNDM-US plasmid. CONCLUSIONS: ArmA and RmtB are the predominant 16S-RMTases in France, but their spread follows two different patterns: (i) dissemination of a conserved genetic support carrying armA in E. coli with high levels of genomic diversity; and (ii) various genetic environments surrounding rmtB in clonally related E. coli.


Assuntos
Farmacorresistência Bacteriana , Escherichia coli , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Escherichia coli/genética , França , Genômica , Metiltransferases/genética , Testes de Sensibilidade Microbiana , Filogenia , Plasmídeos/genética , RNA Ribossômico 16S/genética , beta-Lactamases/genética
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