RESUMO
Aquaculture has been recognized as a hotspot for the emergence and spread of antimicrobial resistance genes conferring resistance to clinically important antibiotics. This review gives insights into studies investigating the prevalence of colistin and carbapenem resistance (CCR) among Gram-negative bacilli in aquaculture. Overall, a high incidence of CCR has been reported in aquatic farms in several countries, with CCR being more prevalent among opportunistic human pathogens such as Acinetobacter nosocomialis, Shewanella algae, Photobacterium damselae, Vibrio spp., Aeromonas spp., as well as members of Enterobacteriaceae family. A high proportion of isolates in these studies exhibited wide-spectrum profiles of antimicrobial resistance, highlighting their multidrug-resistance properties (MDR). Several mobile colistin resistance genes (including, mcr-1, mcr-1.1, mcr-2, mcr-2.1, mcr-3, mcr-3.1, mcr-4.1, mcr-4.3, mcr-5.1, mcr-6.1, mcr-7.1, mcr-8.1, and mcr-10.1) and carbapenemase encoding genes (including, blaOXA-48, blaOXA-55, blaNDM, blaKPC, blaIMI, blaAIM, blaVIM, and blaIMP) have been detected in aquatic farms in different countries. The majority of these were carried on MDR Incompatibility (Inc) plasmids including IncA/C, and IncX4, which have been associated with a wide host range of different sources. Thus, there is a risk for the possible spread of resistance genes between fish, their environments, and humans. These findings highlight the need to monitor and regulate the usage of antimicrobials in aquaculture. A multisectoral and transdisciplinary (One Health) approach is urgently needed to reduce the spread of resistant bacteria and/or resistance genes originating in aquaculture and avoid their global reach.
Assuntos
Carbapenêmicos , Colistina , Animais , Humanos , Colistina/farmacologia , Carbapenêmicos/farmacologia , Prevalência , Saúde Pública , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias Gram-Negativas/genética , Plasmídeos , Aquicultura , Testes de Sensibilidade Microbiana , Farmacorresistência Bacteriana/genéticaRESUMO
Carbapenems are recommended for the treatment of urosepsis caused by extended-spectrum ß-lactamase (ESBL)-producing, multidrug-resistant Escherichia coli; however, due to selection of carbapenem resistance, there is an increasing interest in alternative treatment regimens including the use of ß-lactam-aminoglycoside combinations. We compared the pharmacodynamic activity of piperacillin-tazobactam and amikacin as mono and combination therapy versus meropenem monotherapy against extended-spectrum ß-lactamase (ESBL)-producing, piperacillin-tazobactam resistant E. coli using a dynamic hollow fiber infection model (HFIM) over 7 days. Broth-microdilution was performed to determine the MIC of E. coli isolates. Whole genome sequencing was conducted. Four E. coli isolates were tested in HFIM with an initial inoculum of ~107 CFU/mL. Dosing regimens tested were piperacillin-tazobactam 4.5 g, 6-hourly, plus amikacin 30 mg/kg, 24-hourly, as combination therapy, and piperacillin-tazobactam 4.5 g, 6-hourly, amikacin 30 mg/kg, 24-hourly, and meropenem 1 g, 8-hourly, each as monotherapy. We observed that piperacillin-tazobactam and amikacin monotherapy demonstrated initial rapid bacterial killing but then led to amplification of resistant subpopulations. The piperacillin-tazobactam/amikacin combination and meropenem experiments both attained a rapid bacterial killing (~4-5 log10) within 24 h and did not result in any emergence of resistant subpopulations. Genome sequencing demonstrated that all ESBL-producing E. coli clinical isolates carried multiple antibiotic resistance genes including blaCTX-M-15, blaOXA-1, blaEC, blaTEM-1, and aac(6')-Ib-cr. These results suggest that the combination of piperacillin-tazobactam/amikacin may have a potential role as a carbapenem-sparing regimen, which should be tested in future urosepsis clinical trials.
Assuntos
Amicacina , Escherichia coli , Amicacina/farmacologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Carbapenêmicos , Meropeném/farmacologia , Testes de Sensibilidade Microbiana , Piperacilina/farmacologia , Piperacilina/uso terapêutico , Combinação Piperacilina e Tazobactam , beta-Lactamases/genética , beta-LactamasRESUMO
OBJECTIVES: To develop instrument-free point-of-care methods using recombinase polymerase amplification (RPA) technology coupled with a simple lateral flow detection system to detect Neisseria gonorrhoeae and susceptibility to ciprofloxacin. METHODS: For identification of gonococcal infection, an RPA-based method was developed targeting the gonococcal porA pseudogene (NG-porA-RPA). For ciprofloxacin susceptibility, predictive WT sequences at codons 91 and 95 of the gonococcal gyrA DNase gene were targeted. Given the known complexities of SNP detection using RPA (e.g. the ability to accommodate mismatches) we trialled several different assays incorporating various additional non-template mismatches in the oligonucleotide sequences to reduce affinity for the mutant (resistant) gyrA sequences. Assays were evaluated using a bank of N. gonorrhoeae (nâ=â10) and non-gonococcal (nâ=â5) isolates and a panel of N. gonorrhoeae nucleic acid amplification test (NAAT)-positive clinical sample extracts (nâ=â40). RESULTS: The NG-porA-RPA assay was specific to N. gonorrhoeae and provided a positive percentage agreement (PPA) of 87.5% (35/40) compared with a commercial N. gonorrhoeae NAAT when applied to the 40 clinical sample extracts. For gyrA, the non-template bases successfully reduced banding intensity for double-mutant strains (mutations at both 91 and 95), but not for rarer single-mutant (91 only) strains. The most promising gyrA assay, NG-gyrA-RPA08, correctly detected 83% (25/30) of infections from NAAT-positive clinical samples confirmed to have WT gyrA sequences based on Sanger sequencing. CONCLUSIONS: These proof-of-concept data show that RPA technology has considerable promise for detecting N. gonorrhoeae and associated antibiotic susceptibility and would offer a diagnostic-based stewardship strategy identified as urgently needed by the WHO.
Assuntos
Gonorreia , Neisseria gonorrhoeae , Humanos , Neisseria gonorrhoeae/genética , Ciprofloxacina/farmacologia , Testes de Sensibilidade Microbiana , Farmacorresistência Bacteriana , Antibacterianos/farmacologia , Gonorreia/diagnósticoRESUMO
Combating the ongoing coronavirus disease 2019 (COVID-19) pandemic demands accurate, rapid, and point-of-care testing with fast results to triage cases for isolation and treatment. The current testing relies on reverse transcriptase PCR (RT-PCR), which is routinely performed in well-equipped laboratories by trained professionals at specific locations. However, during busy periods, high numbers of samples queued for testing can delay the test results, impacting efforts to reduce the infection risk. Besides, the absence of well-established laboratories at remote sites and low-resourced environments can contribute to a silent spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). These reasons compel the need to accommodate point-of-care testing for COVID-19 that meets the ASSURED criteria (affordable, sensitive, specific, user-friendly, rapid and robust, equipment-free, and deliverable). This study assessed the agreement and accuracy of the portable Biomeme SARS-CoV-2 system against the gold standard tests. Nasopharyngeal and nasal swabs were used. Of the 192 samples tested using the Biomeme SARS-CoV-2 system, the results from 189 samples (98.4%) were in agreement with the reference standard-of-care RT-PCR testing for SARS-CoV-2. The portable system generated simultaneous results for nine samples in 80 min with high positive and negative percent agreements of 99.0% and 97.8%, respectively. We performed separate testing in a sealed glove box, offering complete biosafety containment. Thus, the Biomeme SARS-CoV-2 system can help decentralize COVID-19 testing and offer rapid test results for patients in remote and low-resourced settings.
Assuntos
Teste de Ácido Nucleico para COVID-19/instrumentação , COVID-19/diagnóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa/instrumentação , Humanos , SARS-CoV-2 , Sensibilidade e EspecificidadeRESUMO
Due to limited treatment options for carbapenem-resistant Acinetobacter baumannii (CR-AB) infections, antibiotic combinations are commonly used. In this study, we explored the potential efficacy of meropenem-sulbactam combination (MEM/SUL) against CR-AB. The checkerboard method was used to screen for synergistic activity of MEM/SUL against 50 clinical CR-AB isolates. Subsequently, time-kill studies against two CR-AB isolates were performed. Time-kill data were described using a semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model. Subsequently, Monte Carlo simulations were performed to estimate the probability of 2-log kill, 1-log kill or stasis at 24-h following combination therapy. The MEM/SUL demonstrated synergy against 28/50 isolates. No antagonism was observed. The MIC50 and MIC90 of MEM/SUL were decreased fourfold, compared to the monotherapy MIC. In the time-kill studies, the combination displayed synergistic killing against both isolates at the highest clinically achievable concentrations. At concentrations equal to the fractional inhibitory concentration, synergism was observed against one isolate. The PK/PD model adequately delineated the data and the interaction between meropenem and sulbactam. The effect of the combination was driven by sulbactam, with meropenem acting as a potentiator. The simulations of various dosing regimens revealed no activity for the monotherapies. At best, the MEM/SUL regimen of 2 g/4 g every 8 h demonstrated a probability of target attainment of 2-log10 kill at 24 h of 34%. The reduction in the MIC values and the achievement of a moderate PTA of a 2-log10 reduction in bacterial burden demonstrated that MEM/SUL may potentially be effective against some CR-AB infections.
Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacocinética , Carbapenêmicos/farmacologia , Farmacorresistência Bacteriana , Meropeném/farmacocinética , Sulbactam/farmacocinética , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/classificação , Antibacterianos/farmacologia , Combinação de Medicamentos , Sinergismo Farmacológico , Humanos , Meropeném/farmacologia , Testes de Sensibilidade Microbiana , Método de Monte Carlo , Sulbactam/farmacologiaRESUMO
Carbapenemase-producing organisms (CPOs) pose a serious clinical threat and rapid detection tools are essential to aid in patient management. We developed rapid and simple molecular tests to detect blaNDM-type and blaVIM-type carbapenemase genes using recombinase polymerase amplification (RPA) combined with a lateral flow detection. The tests could provide results in approximately 15 min when using DNA extracts, with limits of detection of 9.2 copies/µl for the blaNDM-type assay and 7.5 copies/µl for blaVIM-type assay, and successfully detected all isolates harbouring the carbapenemase encoding genes in a panel of 57 isolates. These RPA tests may be suitable for use in low-resource settings to tailor rapid implementation of infection control precautions and antibiotic stewardship.
Assuntos
Bactérias/enzimologia , Proteínas de Bactérias/genética , Técnicas de Amplificação de Ácido Nucleico/métodos , beta-Lactamases/genética , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Bactérias/genética , Proteínas de Bactérias/metabolismo , Primers do DNA/genética , Farmacorresistência Bacteriana , Técnicas de Amplificação de Ácido Nucleico/instrumentação , Recombinases/metabolismo , beta-Lactamases/metabolismoRESUMO
BACKGROUND: Carbapenemase-producing organisms (CPOs) have emerged as antibiotic-resistant bacteria of global concern. Here we assessed the performance of the Carba (beta) assay, a multiplex real-time PCR assay developed by SpeeDx for the detection of key carbapenemase-encoding genes: KPC, NDM, OXA-48-like, IMP-4-like, and VIM. METHODS: DNA extracts of 180 isolates were tested with the Carba (beta) assay, using previously validated in-house TaqMan probe assays for the relevant carbapenemase genes as the reference standard. The Carba (beta) assay was then directly used to screen 460 DNA extracts of faecal specimens, with positive results subjected to the aforementioned in-house assays plus Sanger sequencing. RESULTS: The Carba (beta) assay correctly identified the presence of the respective carbapenemase genes in 154 of 156 isolates and provided negative results for all 24 non-CPO isolates. Two isolates provided positive results for OXA-48-like carbapenemase by the Carba (beta) assay only. The Carba (beta) assay had sensitivities of 100% for all targets, and specificities of 100% for KPC, NDM, IMP-4-like, and VIM targets, and 98.5% for OXA-48-like targets. When applied directly to faecal specimens, eight samples were positive by the Carba (beta) assay, two of which were confirmed by in-house TaqMan probe PCR or DNA sequencing. CONCLUSIONS: The Carba (beta) assay is highly sensitive and specific for detecting key carbapenemase genes in isolates. Further testing is required to assess this assay's suitability for direct screening of clinical specimens.
Assuntos
Bactérias/genética , Proteínas de Bactérias/genética , Reação em Cadeia da Polimerase Multiplex/métodos , Reação em Cadeia da Polimerase em Tempo Real/métodos , beta-Lactamases/genética , Antibacterianos , Bactérias/efeitos dos fármacos , Técnicas Bacteriológicas/métodos , Proteínas de Escherichia coli/genética , Fezes/microbiologia , Humanos , Sensibilidade e EspecificidadeRESUMO
Objectives: To characterize MDR Escherichia coli from bloodstream infections (BSIs) in Australia, New Zealand and Singapore. Methods: We collected third-generation cephalosporin-resistant (3GC-R) E. coli from blood cultures in patients enrolled in a randomized controlled trial from February 2014 to August 2015. WGS was used to characterize antibiotic resistance genes, MLST, plasmids and phylogenetic relationships. Antibiotic susceptibility was determined using disc diffusion and Etest. Results: A total of 70 3GC-R E. coli were included, of which the majority were ST131 (61.4%). BSI was most frequently from a urinary source (69.6%), community associated (62.9%) and in older patients (median age 71 years). The median Pitt score was 1 and ICU admission was infrequent (3.1%). ST131 possessed more acquired resistance genes than non-ST131 (P = 0.003). Clade C1/C2 ST131 predominated (30.2% and 53.5% of ST131, respectively) and these were all ciprofloxacin resistant. All clade A ST131 (n = 6) were community associated. The predominant ESBL types were blaCTX-M (80.0%) and were strongly associated with ST131 (95% carried blaCTX-M), with the majority blaCTX-M-15. Clade C1 was associated with blaCTX-M-14 and blaCTX-M-27, whereas blaCTX-M-15 predominated in clade C2. Plasmid-mediated AmpC genes (mainly blaCMY-2) were frequent (17.1%) but were more common in non-ST131 (P < 0.001) isolates from Singapore and Brisbane. Two strains carried both blaCMY-2 and blaCTX-M. The majority of plasmid replicon types were IncF. Conclusions: In a prospective collection of 3GC-R E. coli causing BSI, community-associated Clade C1/C2 ST131 predominate in association with blaCTX-M ESBLs, although a significant proportion of non-ST131 strains carried blaCMY-2.
Assuntos
Bacteriemia/epidemiologia , Cefalosporinas/farmacologia , Infecções por Escherichia coli/epidemiologia , Escherichia coli/efeitos dos fármacos , beta-Lactamases/genética , Idoso , Idoso de 80 Anos ou mais , Austrália/epidemiologia , Técnicas de Tipagem Bacteriana , Farmacorresistência Bacteriana/genética , Escherichia coli/classificação , Escherichia coli/genética , Infecções por Escherichia coli/sangue , Feminino , Genoma Bacteriano , Humanos , Masculino , Pessoa de Meia-Idade , Tipagem de Sequências Multilocus , Nova Zelândia/epidemiologia , Filogenia , Prevalência , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Singapura/epidemiologia , Sequenciamento Completo do Genoma , beta-Lactamases/biossínteseRESUMO
The emergence of pan-resistant Klebsiella pneumoniae strains is an increasing concern. In the present study, we describe a cluster of 9 pan-resistant K. pneumoniae sequence type 147 (ST147) isolates encountered in 4 patients over nearly 1 year in 3 hospitals of the United Arab Emirates (UAE). The isolates exhibited highly similar genotypes. All produced chromosomally encoded OXA-181, and the majority also produced the NDM-5 carbapenemase. As with the previously described single isolate from the UAE, MS6671, the mgrB was disrupted by a functional, ISEcp1-driven blaOXA-181 insertion causing resistance to carbapenems. The mutation was successfully complemented with an intact mgrB gene, indicating that it was responsible for colistin resistance. blaNDM-5 was located within a resistance island of an approximately 100-kb IncFII plasmid carrying ermB, mph(A), blaTEM-1B, rmtB, blaNDM-5, sul1, aadA2, and dfrA12 resistance genes. Sequencing this plasmid (pABC143-NDM) revealed that its backbone was nearly identical to that of plasmid pMS6671E from which several resistance genes, including blaNDM-5, had been deleted. More extensive similarities of the backbone and the resistance island were found between pABC143C-NDM and the blaNDM-5-carrying IncFII plasmids of two K. pneumoniae ST147 isolates from South Korea, one of which was colistin resistant, and both also produced OXA-181. Notably, one of these strains was isolated from a patient transferred from the UAE. Our data show that this pan-resistant clone has an alarming capacity to maintain itself over an extended period of time and is even likely to be transmitted internationally.
Assuntos
Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Klebsiella pneumoniae/enzimologia , Klebsiella pneumoniae/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Colistina/farmacologia , Genótipo , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Plasmídeos/genética , República da Coreia , Emirados Árabes Unidos , beta-Lactamases/genética , beta-Lactamases/metabolismoRESUMO
The carbapenem resistance determinant blaNDM-1 has been found in various Gram-negative bacteria and upon different plasmid replicon types (Inc). Here, we present four patients within two hospitals in Pakistan harboring between two and four NDM-1-producing Gram-negative bacilli of different species coresident in their stool samples. We characterize the blaNDM-1 genetic contexts of these 11 NDM-1-producing Gram-negative bacilli in addition to other antimicrobial resistance mechanisms, plasmid replicon profiles, and sequence types (STs) in order to understand the underlying acquisition mechanisms of carbapenem resistance within these bacteria. Two common plasmid types (IncN2 and IncA/C) were identified to carry blaNDM-1 among the six different bacterial species isolated from the four patients. Two of these strains were novel Citrobacter freundii ST 20 and ST 21. The same IncN2-type blaNDM-1 genetic context was found in all four patients and within four different species. The IncA/C-type blaNDM-1 genetic context was found in two different species and in two of the four patients. Combining genetic context characterization with other molecular epidemiology methods, we were able to establish the molecular epidemiological links between genetically unrelated bacterial species by linking their acquisition of an IncN2 or IncA/C plasmid carrying blaNDM-1 for carbapenem resistance. By combining plasmid characterization and in-depth genetic context assessment, this analysis highlights the importance of plasmids in antimicrobial resistance. It also provides a novel approach for investigating the underlying mechanisms of blaNDM-1-related spread between bacterial species and genera via plasmids.
Assuntos
Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Farmacorresistência Bacteriana/genética , Bactérias Gram-Negativas/genética , beta-Lactamases/genética , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/enzimologia , Bactérias Gram-Negativas/isolamento & purificação , Humanos , Paquistão , Plasmídeos/genética , beta-Lactamases/metabolismoRESUMO
The molecular epidemiology and mechanisms of resistance of carbapenem-resistant Acinetobacter baumannii (CRAB) were determined in hospitals in the states of the Cooperation Council for the Arab States of the Gulf (Gulf Cooperation Council [GCC]), namely, Saudi Arabia, United Arab Emirates, Oman, Qatar, Bahrain, and Kuwait. Isolates were subjected to PCR-based detection of antibiotic resistance genes and repetitive sequence-based PCR (rep-PCR) assessments of clonality. Selected isolates were subjected to multilocus sequence typing (MLST). We investigated 117 isolates resistant to carbapenem antibiotics (either imipenem or meropenem). All isolates were positive for OXA-51. The most common carbapenemases were the OXA-23-type, found in 107 isolates, followed by OXA-40-type (OXA-24-type), found in 5 isolates; 3 isolates carried the ISAba1 element upstream of blaOXA-51-type. No OXA-58-type, NDM-type, VIM-type, or IMP-type producers were detected. Multiple clones were detected with 16 clusters of clonally related CRAB. Some clusters involved hospitals in different states. MLST analysis of 15 representative isolates from different clusters identified seven different sequence types (ST195, ST208, ST229, ST436, ST450, ST452, and ST499), as well as three novel STs. The vast majority (84%) of the isolates in this study were associated with health care exposure. Awareness of multidrug-resistant organisms in GCC states has important implications for optimizing infection control practices; establishing antimicrobial stewardship programs within hospital, community, and agricultural settings; and emphasizing the need for establishing regional active surveillance systems. This will help to control the spread of CRAB in the Middle East and in hospitals accommodating transferred patients from this region.
Assuntos
Infecções por Acinetobacter/epidemiologia , Acinetobacter baumannii/classificação , Acinetobacter baumannii/enzimologia , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Resistência beta-Lactâmica , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/isolamento & purificação , Pré-Escolar , Análise por Conglomerados , Feminino , Genótipo , Hospitais , Humanos , Lactente , Masculino , Oriente Médio/epidemiologia , Epidemiologia Molecular , Tipagem de Sequências Multilocus , Reação em Cadeia da Polimerase , beta-Lactamases/genéticaRESUMO
The increasing emergence and spread of antimicrobial resistance (AMR) is a serious public health issue. Increasing the awareness of the general public about appropriate antibiotic use is a key factor for combating this issue. Several public media campaigns worldwide have been launched; however, such campaigns can be costly and the outcomes are variable and difficult to assess. Social media platforms, including Twitter, Facebook, and YouTube, are now frequently utilized to address health-related issues. In many geographical locations, such as the countries of the Gulf Cooperation Council (GCC) States (Saudi Arabia, United Arab Emirates, Kuwait, Oman, Qatar, and Bahrain), these platforms are becoming increasingly popular. The socioeconomic status of the GCC states and their reliable communication and networking infrastructure has allowed the penetration and scalability of these platforms in the region. This might explain why the Saudi Ministry of Health is using social media platforms alongside various other media platforms in a large-scale public awareness campaign to educate at-risk communities about the recently emerged Middle East respiratory syndrome coronavirus (MERS-CoV). This paper discusses the potential for using social media tools as cost-efficient and mass education platforms to raise awareness of appropriate antibiotic use in the general public and in the medical communities of the Arabian Peninsula.
Assuntos
Antibacterianos/uso terapêutico , Promoção da Saúde/estatística & dados numéricos , Mídias Sociais/estatística & dados numéricos , Humanos , Oriente MédioRESUMO
SUMMARY Infections due to Gram-negative bacilli (GNB) are a leading cause of morbidity and mortality worldwide. The extent of antibiotic resistance in GNB in countries of the Gulf Cooperation Council (GCC), namely, Saudi Arabia, United Arab Emirates, Kuwait, Qatar, Oman, and Bahrain, has not been previously reviewed. These countries share a high prevalence of extended-spectrum-ß-lactamase (ESBL)- and carbapenemase-producing GNB, most of which are associated with nosocomial infections. Well-known and widespread ß-lactamases genes (such as those for CTX-M-15, OXA-48, and NDM-1) have found their way into isolates from the GCC states. However, less common and unique enzymes have also been identified. These include PER-7, GES-11, and PME-1. Several potential risk factors unique to the GCC states may have contributed to the emergence and spread of ß-lactamases, including the unnecessary use of antibiotics and the large population of migrant workers, particularly from the Indian subcontinent. It is clear that active surveillance of antimicrobial resistance in the GCC states is urgently needed to address regional interventions that can contain the antimicrobial resistance issue.
Assuntos
Proteínas de Bactérias/biossíntese , Bactérias Gram-Negativas/enzimologia , Infecções por Bactérias Gram-Negativas/microbiologia , beta-Lactamases/biossíntese , Antibacterianos/farmacologia , Carbapenêmicos , Humanos , Oriente Médio/epidemiologia , Vigilância em Saúde Pública , Resistência beta-LactâmicaRESUMO
The molecular epidemiology and mechanisms of resistance of carbapenem-resistant Enterobacteriaceae (CRE) were determined in hospitals in the countries of the Gulf Cooperation Council (GCC), namely, Saudi Arabia, United Arab Emirates, Oman, Qatar, Bahrain, and Kuwait. Isolates were subjected to PCR-based detection of antibiotic-resistant genes and repetitive sequence-based PCR (rep-PCR) assessments of clonality. Sixty-two isolates which screened positive for potential carbapenemase production were assessed, and 45 were found to produce carbapenemase. The most common carbapenemases were of the OXA-48 (35 isolates) and NDM (16 isolates) types; 6 isolates were found to coproduce the OXA-48 and NDM types. No KPC-type, VIM-type, or IMP-type producers were detected. Multiple clones were detected with seven clusters of clonally related Klebsiella pneumoniae. Awareness of CRE in GCC countries has important implications for controlling the spread of CRE in the Middle East and in hospitals accommodating patients transferred from the region.
Assuntos
Proteínas de Bactérias/genética , Infecções por Escherichia coli/epidemiologia , Proteínas de Escherichia coli/genética , Escherichia coli/enzimologia , Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae/enzimologia , beta-Lactamases/genética , Antibacterianos/metabolismo , Proteínas de Bactérias/metabolismo , Carbapenêmicos/metabolismo , Escherichia coli/genética , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/microbiologia , Proteínas de Escherichia coli/metabolismo , Humanos , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/isolamento & purificação , Testes de Sensibilidade Microbiana , Oriente Médio/epidemiologia , Ocitocina/análogos & derivados , Ocitocina/metabolismo , beta-Lactamases/metabolismoRESUMO
BACKGROUND: Klebsiella pneumoniae is a major bacterial and opportunistic human pathogen, increasingly recognized as a healthcare burden globally. The convergence of resistance and virulence in K. pneumoniae strains has led to the formation of hypervirulent and multidrug-resistant strains with dual risk, limiting treatment options. K. pneumoniae clones are known to emerge locally and spread globally. Therefore, an understanding of the dynamics and evolution of the emerging strains in hospitals is warranted to prevent future outbreaks. METHODS: In this study, we conducted an in-depth genomic analysis on a large-scale collection of 328 multidrug-resistant (MDR) K. pneumoniae strains recovered from 239 patients from a single major hospital in the western coastal city of Jeddah in Saudi Arabia from 2014 through 2022. We employed a broad range of phylogenetic and phylodynamic methods to understand the evolution of the predominant clones on epidemiological time scales, virulence and resistance determinants, and their dynamics. We also integrated the genomic data with detailed electronic health record (EHR) data for the patients to understand the clinical implications of the resistance and virulence of different strains. RESULTS: We discovered a diverse population underlying the infections, with most strains belonging to Clonal Complex 14 (CC14) exhibiting dominance. Specifically, we observed the emergence and continuous expansion of strains belonging to the dominant ST2096 in the CC14 clade across hospital wards in recent years. These strains acquired resistance mutations against colistin and extended spectrum ß-lactamase (ESBL) and carbapenemase genes, namely blaOXA-48 and blaOXA-232, located on three distinct plasmids, on epidemiological time scales. Strains of ST2096 exhibited a high virulence level with the presence of the siderophore aerobactin (iuc) locus situated on the same mosaic plasmid as the ESBL gene. Integration of ST2096 with EHR data confirmed the significant link between colonization by ST2096 and the diagnosis of sepsis and elevated in-hospital mortality (p-value < 0.05). CONCLUSIONS: Overall, these results demonstrate the clinical significance of ST2096 clones and illustrate the rapid evolution of an emerging hypervirulent and MDR K. pneumoniae in a clinical setting.
Assuntos
Klebsiella pneumoniae , Klebsiella , Humanos , Klebsiella/genética , Centros de Atenção Terciária , Filogenia , Plasmídeos/genética , beta-Lactamases/genética , AntibacterianosRESUMO
Background: Due to their prevalence worldwide, the ß-lactamases CTX-M and plasmid-mediated CMY-2 are important antimicrobial resistance enzymes in a clinical setting. While culture- and PCR-based detection methods exist for these targets, they are time consuming and require specialist equipment and trained personnel to carry out. Methods: In this study, three rapid diagnostic single-plex and a prototype triplex assay were developed, using recombinase polymerase amplification with lateral flow detection (RPA-LF), and tested for their sensitivity and specificity using two isolate DNA panels (nâ=â90 and nâ=â120 isolates). In addition, the RPA-LF assays were also tested with a small number of faecal extract samples (nâ=â18). Results: The RPA-LF assays were able to detect bla CXT-M-group-1, bla CTX-M-group-9 and bla CMY-2-type variants with high sensitivity (82.1%-100%) and specificity (100%) within a short turnaround time (15-20â min for amplification and detection). Conclusions: RPA-LF assays developed in this study have the potential to be used at or close to the point of care, as well as in low-resource settings, producing rapid results to support healthcare professionals in their treatment decisions.
RESUMO
BACKGROUND: During the COVID-19 pandemic, countries around the world implemented various interventions to manage the spread of respiratory illnesses, including influenza. However, there is a lack of studies that have assessed the influence of COVID-19 on influenza prevalence in Saudi Arabia. In this study, we aimed to evaluate the prevalence of positive influenza cases before and during the COVID-19 pandemic in relation to the mitigation measures and policy initiatives in Saudi Arabia. METHODS: A multicenter, time-series cross-sectional study was conducted to evaluate influenza prevalence before and during the COVID-19 pandemic between 01/01/2017 and 31/12/2021. This study included all patients who were screened for influenza infection at healthcare facilities across Saudi Arabia using polymerase chain reaction (PCR). The primary outcome was to determine the prevalence of influenza infections before and during the COVID-19 pandemic, while the secondary outcome was to describe the demographic data and comorbidities of the included patients in both periods. RESULTS: During the study period, 5238 cases were identified based on a positive PCR result for influenza virus. The yearly number of influenza cases in the pre-COVID-19 period was 1123 (2.03 %), 1075 (1.63 %), and 1883 (2.20 %) cases in 2017, 2018, and 2019, respectively. On the other hand, the number of cases during the COVID-19 pandemic was 417 (0.63 %) and 740 (1.27 %) in 2020 and 2021, respectively, with a comparable number of performed tests. Patients infected with the influenza virus between 2020 and 2021 were older than patients who were infected before the COVID-19 pandemic. CONCLUSION: The study found a lower number of influenza cases during the COVID-19 pandemic, with no clear peak during November and December 2020 and 2021.
Assuntos
COVID-19 , Influenza Humana , Humanos , COVID-19/epidemiologia , Influenza Humana/epidemiologia , Pandemias , Estudos Transversais , Fatores de Tempo , Arábia Saudita/epidemiologiaRESUMO
Severe acute respiratory syndrome coronavirus (SARS-CoV-2) emerged in December 2019 and caused a global pandemic of the Coronavirus Disease 2019 (COVID-19). More than 170 million cases have been reported worldwide with mortality rate of 1-3%. The detection of SARS-CoV-2 by molecular testing is limited to acute infections, therefore serological studies provide a better estimation of the virus spread in a population. This study aims to evaluate the seroprevalence of SARS-CoV-2 in the major city of Riyadh, Saudi Arabia during the sharp increase of the pandemic, in June 2020. Serum samples from non-COVID patients (n = 432), patients visiting hospitals for other complications and confirmed negative for COVID-19, and healthy blood donors (n = 350) were collected and evaluated using an in-house enzyme-linked immunosorbent assay (ELISA). The overall percentage of positive samples was 7.80% in the combined two populations (n = 782). The seroprevalence was lower in the blood donors (6%) than non-COVID-19 patients (9.25%), p = 0.0004. This seroprevalence rate is higher than the documented cases, indicating asymptomatic or mild unreported COVID-19 infections in these two populations. This warrants further national sero-surveys and highlights the importance of real-time serological surveillance during pandemics.
RESUMO
Pseudomonas otitidis is a rare and unique species among the Pseudomonas genus that has not been previously reported as a cause of male genitourinary tract infection. In this report, we describe a case of a 20-year-old immunocompetent male who presented with recurrent epididymo-orchitis, which was initially misidentified as Vibrio vulnificus and treated successfully. The causative agent could not be identified appropriately using the available routine methods, but a final identification was established using 16S rRNA targeted sequencing followed by whole-genome sequencing.
RESUMO
BACKGROUND: Patients with underlying heart failure (HF) in the setting of COVID-19 who require admission to the intensive care unit (ICU) might present with a unique set of challenges. This study aims to extensively describe the characteristics and outcomes of patients with HF who were admitted to ICU with COVID-19. METHODS: We conducted a multicenter retrospective analysis for all adult patients with HF and an objectively confirmed diagnosis of COVID-19 who were admitted to ICUs between March 1 and August 31, 2020, in Saudi Arabia. RESULTS: A total of 723 critically ill patients with COVID-19 were admitted into ICUs during the study period: 59 patients with HF and 664 patients with no HF before admission to ICU. Patients with HF had statistically significant more comorbidities, including diabetes mellitus, hypertension, dyslipidemia, atrial fibrillation, and acute coronary syndrome. Moreover, higher baseline severity scores (APACHE II & SOFA score) and nutritional risk (NUTRIC score) were observed in HF patients. Overall, patients with HF had more in-hospital and ICU deaths in comparison to patients without HF: (64.3% vs. 44.6%, P-value <0.01) and (54.5% vs. 39%, P-value = 0.02), respectively. Patients with HF had a similar incidence of thrombosis, ICU length of stay, duration of mechanical ventilation, and hospital length of stay compared to patients with no HF. CONCLUSION: In this study, patients with HF had more in-hospital and ICU deaths than patients with no HF. Thus, history of HF could be used to help direct case management during hospitalization and possibly dictate proactive COVID-19 care.