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1.
BMC Infect Dis ; 20(1): 193, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32131752

RESUMO

BACKGROUND: Microbial infection is the main cause of increased morbidity and mortality in burn patients, especially infections caused by multiple drug-resistant organisms (MDRO). The purpose of this study was to explore major microbial trends in burn patients. METHODS: This retrospective study was conducted at burn wards and intensive care units, where burn patients were admitted following an event of dust explosion. Data were collected for a number of variables including severity of burns, demographic and clinical characteristics, laboratory data, and therapeutic devices. RESULTS: A total of 1132 specimens were collected from 37 hospitalized burn patients with mean TBSA of 46.1%.The most commonly isolated species were Staphylococcus spp. (22.4%). The highest rate of antibiotic resistance was observed in carbapenem-resistant A. baumannii (14.6%), followed by methicillin-resistant S. aureus (11.3%). For each additional 10% TBSA, the isolation of MDRO increased 2.58-17.57 times (p < 0.05); for each additional 10% of the third-degree burn severity, the risk of MDRO significantly decreased by 47% (95% CI, 0.38-0.73, p < 0.001) by Cox model. CONCLUSIONS: The proportion of overall microbial isolates increased with the increase in TBSA and duration of time after burns. The extent of TBSA was the most important factor affecting MDRO.


Assuntos
Traumatismos por Explosões/microbiologia , Queimaduras por Inalação/microbiologia , Poeira , Explosões , Centros de Atenção Terciária , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/isolamento & purificação , Adolescente , Adulto , Antibacterianos/uso terapêutico , Superfície Corporal , Carbapenêmicos/efeitos adversos , Carbapenêmicos/uso terapêutico , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Feminino , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Estudos Retrospectivos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Fatores de Tempo , Adulto Jovem
2.
Medicine (Baltimore) ; 99(10): e19466, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32150105

RESUMO

Multidrug-resistant bacterial (MDRB) infections have been difficult to treat clinically. Tigecycline (TIG) has several advantages, especially in the treatment of severe infections. Many clinicians have considered increasing the TIG dose to improve the efficacy of this molecule. The safety and efficacy of high-dose TIG in elderly patients with MDRB infections were investigated in this study.We conducted a retrospective analysis of the elderly patients with MDRB infections who were treated at the First Affiliated Hospital. A total of 106 patients received a conventional dose (CD-TIG group: 50 mg every 12 hours) of TIG and 51 received a high dose (HD-TIG group: 100 mg every 12 hours). The data from all patients were collected for examining the clinical features and performing the microbiological analysis. The safety profile and efficacy of the HD regimen were investigated.The clinical efficacy and microbiological eradication in the patients with MDRB infection were higher in the HD-TIG group than the CD-TIG group. The independent predictors of clinical cure were the use of TIG at HD (odd ratio [OR], 5.129; 95% confidence interval [CI] [1.890, 13.921]; P = .001) and microbiological eradication (OR, 3.049; 95% CI, [1.251, 7.430]; P = .014). In the ventilator-associated pneumonia (VAP) and bloodstream infection (BSI) subgroups, the sole independent predictor of clinical cure was the HD of TIG, and no significant adverse events were observed. The occurrence of multidrug-resistant Acinetobacter baumannii infection and an MIC value of 1 to 2 g/mL for TIG were independently associated with clinical failure in the VAP subgroup.HDs of TIG was found to associate with better clinical efficacy and microbiological eradication than its CDs in the elderly patients with MDRB infections. In the VAP and BSIs subgroups, administration of HDs of TIG was associated with better outcomes.


Assuntos
Infecções por Acinetobacter/tratamento farmacológico , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Tigeciclina/uso terapêutico , APACHE , Acinetobacter baumannii/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Tigeciclina/administração & dosagem , Tigeciclina/farmacologia , Resultado do Tratamento
3.
BMC Infect Dis ; 20(1): 92, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32000693

RESUMO

BACKGROUND: Multi-drug resistant (MDR) Acinetobacter baumannii and Pseudomonas aeruginosa are major causes of nosocomial infections globally. They are the current World Health Organization critical priority pathogens for resistance, Antimicrobial resistance (AMR) surveillance and discovery of new antibiotics. However, there is paucity of data on nosocomial infections (NIs) caused by such superbugs in Ethiopia. Therefore, this study determined the magnitude and profile of nosocomial MDR A. baumannii and P. aeruginosa infections among patients hospitalized at Felegehiwot referral hospital, Northwest Ethiopia. METHODS: A cross-sectional study was conducted at Felegehiwot referral hospital from April 1 to July 31, 2018. A total of 238 patients with blood stream, urinary tract and surgical site NIs were enrolled conveniently. Either blood, urine and wound swab specimens were collected and processed using standard bacteriological procedures. A. baumannii and P. aeruginosa isolates were identified using standard bacteriological techniques and confirmed by automated Vitek2 Compact. Antimicrobial susceptibility testing on isolates was performed using the disk diffusion technique. The results were interpreted as per the standard zone sizes of Clinical and Laboratory Standards Institute.Chi-square test was done to determine associations among variables. P value < 0.05 was considered statistical significant. RESULTS: The median age of participants was 29 years. Overall,20(8.4%) of patients had nosocomial MDR A. baumannii and P. aeruginosa infections. The proportion of nosocomial MDR blood stream, urinary tract and surgical site infections were 13(8.9%), 5(8.3%) and 2 (6.3%), respectively. Patients with NI had lower mean age (24.9 years) (P = 0.035). All isolates of NIs were from patients with intravenous catheterization. The frequency of NI was 9(3.8%) for MDR A. baumannii and 11(4.6%) for MDR P.aeruginosa. A. baumannii and P. aeruginosa isolates were 100% MDR. All isolates of A. baumannii and P. aeruginosa were 100% resistant to ampicillin and piperacillin.A. baumannii isolates were 33.3 and 44.5% resistance against meropenem and ciprofloxacin, respectively while P.aeruginosa isolates revealed 36.4 and 45.5% resistance against ciprofloxacin and meropenem, respectively. CONCLUSIONS: Health care associated infections of MDR A.baumannii and P. aeruginosa are critical problems in the study area. Therefore, urgent focused interventions required to contain the spreading of MDR NIs. Treatment of NIs for patients on health care should be guided by antimicrobial susceptibility testing.


Assuntos
Infecções por Acinetobacter/tratamento farmacológico , Acinetobacter baumannii/isolamento & purificação , Bacteriemia/tratamento farmacológico , Infecção Hospitalar/tratamento farmacológico , Farmacorresistência Bacteriana Múltipla , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/isolamento & purificação , Infecção da Ferida Cirúrgica/tratamento farmacológico , Infecções Urinárias/tratamento farmacológico , Adolescente , Adulto , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Estudos Transversais , Etiópia , Feminino , Humanos , Lactente , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Encaminhamento e Consulta , Infecção da Ferida Cirúrgica/microbiologia , Centros de Atenção Terciária , Infecções Urinárias/microbiologia , Adulto Jovem
4.
Ann Clin Microbiol Antimicrob ; 19(1): 2, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31941492

RESUMO

BACKGROUND: Acinetobacter baumannii is a Gram-negative opportunistic pathogen with a notorious reputation of being resistant to antimicrobial agents. The capability of A. baumannii to persist and disseminate between healthcare settings has raised a major concern worldwide. METHODS: Our study investigated the antibiotic resistance features and molecular epidemiology of 52 clinical isolates of A. baumannii collected in Pakistan between 2013 and 2015. Antimicrobial susceptibility patterns were determined by the agar disc diffusion method. Comparative sequence analyses of the ampC and blaOXA-51-like alleles were used to assign the isolates into clusters. The whole genomes of 25 representative isolates were sequenced using the MiSeq Desktop Sequencer. Free online applications were used to determine the phylogeny of genomic sequences, retrieve the multilocus sequence types (ST), and detect acquired antimicrobial resistance genes. RESULTS: Overall, the isolates were grouped into 7 clusters and 3 sporadic isolates. The largest cluster, Ab-Pak-cluster-1 (blaOXA-66 and ISAba1-ampC-19) included 24 isolates, belonged to ST2 and International clone (IC) II, and was distributed between two geographical far-off cities, Lahore and Peshawar. Ab-Pak-clusters-2 (blaOXA-66, ISAba1-ampC-2), and -3 (blaOXA-66, ISAba1-ampC-20) and the individual isolate Ab-Pak-Lah-01 (ISAba1-blaOXA-66, ISAba1-ampC-2) were also assigned to ST2 and IC II. On the other hand, Ab-Pak-clusters-4 (blaOXA-69, ampC-1), -5 (blaOXA-69, ISAba1-ampC-78), and -6A (blaOXA-371, ISAba1-ampC-3) belonged to ST1, while Ab-Pak-cluster-6B (blaOXA-371, ISAba1-ampC-8) belonged to ST1106, with both ST1 and ST1106 being members of IC I. Five isolates belonged to Ab-Pak-cluster-7 (blaOXA-65, ampC-43). This cluster corresponded to ST158, showed a well-delineated position on the genomic phylogenetic tree, and was equipped with several antimicrobial resistance genes including blaOXA-23 and blaGES-11. CONCLUSIONS: Our study detected the occurrence of 7 clusters of A. baumannii in Pakistan. Altogether, 6/7 of the clusters and 45/52 (86.5%) of the isolates belonged to IC I (n = 9) or II (n = 36), making Pakistan no exception to the global domination of these two clones. The onset of ST158 in Pakistan marked a geographical dispersal of this clone beyond the Middle East and brought up the need for a detailed characterization.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Farmacorresistência Bacteriana/genética , Epidemiologia Molecular , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/epidemiologia , Acinetobacter baumannii/genética , Acinetobacter baumannii/isolamento & purificação , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Infecção Hospitalar , Genoma Bacteriano , Humanos , Testes de Sensibilidade Microbiana , Infecções Oportunistas , Paquistão/epidemiologia , Filogenia
5.
BMC Infect Dis ; 20(1): 45, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31941459

RESUMO

BACKGROUND: Acinetobacter baumannii is a gram-negative aerobic bacillus that is commonly causes of hospital-acquired infections. Community-acquired pneumonia caused by Acinetobacter baumannii (CAP-Ab) is rare but fatal if diagnosis and treatment are delayed. Conventional culture of clinical specimens is the main method for clinical diagnosis of A. baumannii infections which may suffer from limited positive rate and is time consuming. Timely and precise diagnosis of CAP-Ab remains challenging. CASE PRESENTATION: A 66-year-old man with 24 h history of acute fever and dyspnea was admitted to our hospital. He was diagnosed as severe community acquired pneumonia (CAP), septic shock, respiratory failure and acute kidney injury. Next-generation sequencing (NGS) was performed on the patient's sputum and blood, which identified numerous A. baumannii nucleotide sequences in the sample of sputum and led to the rapid diagnosis and treatment of community acquired pneumonia caused by A. baumannii. This result was confirmed by subsequent sputum culture. CONCLUSIONS: This case described that the successful application of the next generation sequencing assisting the speedy diagnosis of A. baumannii infection provides a new idea for the timely diagnosis of CAP-Ab and highlights that NGS is a promising tool in rapid etiological diagnosis of acute and severe infectious diseases.


Assuntos
Infecções por Acinetobacter/diagnóstico , Acinetobacter baumannii/genética , Infecções Comunitárias Adquiridas/diagnóstico , Sequenciamento de Nucleotídeos em Larga Escala , Pneumonia Bacteriana/diagnóstico , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/microbiologia , Lesão Renal Aguda/complicações , Idoso , Antibacterianos/uso terapêutico , China , Infecções Comunitárias Adquiridas/sangue , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecção Hospitalar , Dispneia/complicações , Febre/complicações , Hospitalização , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pneumonia Bacteriana/sangue , Pneumonia Bacteriana/tratamento farmacológico , Insuficiência Respiratória/complicações , Choque Séptico/complicações , Escarro/microbiologia , Resultado do Tratamento
6.
J Appl Microbiol ; 128(1): 15-27, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31102552

RESUMO

Acinetobacter baumannii causes several nosocomial infections and poses major threat when it is multidrug resistant. Even pan drug-resistant strains have been reported in some countries. The intensive care unit (ICU) mortality rate ranged from 45.6% to 60.9% and it is as high as 84.3% when ventilator-associated pneumonia was caused by XDR (extensively drug resistant) A. baumannii. Acinetobacter baumannii constituted 9.4% of all Gram-negative organisms throughout the hospital and 22.6% in the ICUs according to a study carried out in an Indian hospital. One of the major factors contributing to drug resistance in A. baumannii infections is biofilm development. Quorum sensing (QS) facilitates biofilm formation and therefore the search for 'quorum quenchers' has increased recently. Such compounds are expected to inhibit biofilm formation and hence reduce/prevent development of drug resistance in the bacteria. Some of these compounds also target synthesis of some virulence factors (VF). Several candidate drugs have been identified and are at various stages of drug development. Since quorum quenching, inhibition of biofilm formation and inhibition of VF synthesis do not pose any threat to the DNA replication and cell division of the bacteria, chances of resistance development to such compounds is presumably rare. Thus, these compounds ideally qualify as adjunct therapeutics and could be administered along with an antibiotic to reduce chances of resistance development and also to increase the effectiveness of antimicrobial therapy. This review describes the state-of-art in QS process in Gram-negative bacteria in general and in A. baumannii in particular. This article elaborates the nature of QS mediators, their characteristics, and the methods for their detection and quantification. Various potential sites in the QS pathway have been highlighted as drug targets and the candidate quorum quenchers which inhibit the mediator's synthesis or function are enlisted.


Assuntos
Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/fisiologia , Percepção de Quorum , Infecções por Acinetobacter/tratamento farmacológico , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/patogenicidade , Acil-Butirolactonas/metabolismo , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Proteínas de Bactérias/metabolismo , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Desenvolvimento de Medicamentos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/genética , Percepção de Quorum/efeitos dos fármacos , Fatores de Virulência/metabolismo
7.
S Afr Med J ; 110(1): 49-54, 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31865943

RESUMO

BACKGROUND: Drug-resistant Acinetobacter species present serious therapeutic and infection control policy challenges globally. Although aminoglycosides have played a crucial role in the treatment of infections with multidrug-resistant (MDR) Acinetobacter spp., recent reports indicate that these bacteria are developing resistance to aminoglycosides around the globe. OBJECTIVES: To determine the association between amikacin resistance and clinical outcomes of patients. The minimum inhibitory concentrations (MICs) of amikacin against Acinetobacter spp. and genes associated with resistance were also investigated. METHODS: Clinical information from 107 patients with Acinetobacter spp. cultured from clinical specimens was recorded during ward rounds at an academic complex hospital in KwaZulu-Natal Province, South Africa, including clinical outcomes, history of antibiotics prescribed and microbiological investigations. The 107 Acinetobacter isolates were investigated for susceptibility to antimicrobial agents in use at local hospitals. Genes related to amikacin resistance (aphA6 and aacA4) were investigated by polymerase chain reaction (PCR) and sequencing. Analysis was performed on the relationship between clinical outcomes and antimicrobial resistance patterns, as well as on the amikacin MICs in resistant isolates (n=6) v. their PCR results. RESULTS: The majority (5/6, 83.3%) of patients with amikacin-resistant Acinetobacter infection were discharged, and 1/6 (16.7%) died. No underlying clinical factors were significantly associated with clinical outcome. Amikacin resistance was observed in 6/107 isolates (5.6%), with MICs of 32 µg/mL (n=3) and ≥64 µg/mL (n=3) for the amikacin-resistant isolates. All 6 of these isolates were also extensively drug-resistant (XDR). The aphA6 gene (797 base pair) was detected in all amikacin-resistant isolates. CONCLUSIONS: Most tested Acinetobacter isolates were susceptible to amikacin, underscoring the crucial role of this antibiotic in the treatment of MDR Acinetobacter spp. in our hospital. The emergence of XDR isolates is of serious concern and necessitates close monitoring and surveillance.


Assuntos
Infecções por Acinetobacter/microbiologia , Acinetobacter/efeitos dos fármacos , Amicacina/farmacologia , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Farmacorresistência Bacteriana/genética , Genes Bacterianos , Centros Médicos Acadêmicos , Fosfatase Ácida , Acinetobacter/genética , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Amicacina/uso terapêutico , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , DNA Bacteriano/análise , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , África do Sul , Resultado do Tratamento , Adulto Jovem
8.
BMC Infect Dis ; 19(1): 829, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31590644

RESUMO

BACKGROUND: Acinetobacter baumannii is an increasingly worrying organism in the healthcare setting, due to its multidrug resistance and persistence. Prolonged hospitalisation, immunocompromised patients and excessive antibiotic exposure all contribute to increasing the risk of A. baumannii infections, which makes cancer patients a significant risk group. This study aims to investigate the dissemination of A. baumannii at the National Cancer Institute (NCI) in Cairo - Egypt. METHODS: All bacterial isolates were typed using Multi-locus Sequence Typing (MLST) to characterise the epidemiology of isolates. The intrinsic OXA-51-like, and the acquired carbapanemases OXA-23, - 24/40, - 58, NDM, IMP, and VIM were also amplified and sequenced to genetically identify mechanisms of carbapenem resistance. RESULTS: MLST results show a high degree of multi-clonal dissemination, with 18 different Sequence Types (STs) identified, including 5 novel. The majority of isolates belonged to International Clone (IC) 2, and carbapenem resistance was detected in 93% of isolates and mediated by blaOXA-23, blaOXA-58, blaNDM-1 and blaVIM-1. We also report the presence of a resistant ST732 (OXA-378) which has been previously identified in migratory birds. CONCLUSIONS: Multiple highly resistant clones were identified in a Cancer hospital in Cairo. It is vital that clinicians and healthcare workers are aware of the population of A. baumannii present in order to have appropriate treatment and infection control practices.


Assuntos
Infecções por Acinetobacter/diagnóstico , Infecções por Acinetobacter/epidemiologia , Acinetobacter baumannii/genética , Infecções por Acinetobacter/tratamento farmacológico , Acinetobacter baumannii/isolamento & purificação , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Técnicas de Tipagem Bacteriana , Institutos de Câncer , Carbapenêmicos/efeitos adversos , Carbapenêmicos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Egito/epidemiologia , Feminino , Genes Bacterianos , Genótipo , Pessoal de Saúde , Humanos , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , beta-Lactamases
9.
BMC Infect Dis ; 19(1): 900, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31660862

RESUMO

BACKGROUND: Carbapenem resistance among Acinetobacter species has become a life-threatening problem. As a last resort in the treatment of gram-negative bacteria infection, resistance to colistin is also a serious problem. The aim of study was to analyze the mechanism of resistance and perform genotyping of carbapenem-resistant Acinetobacter from clinical infection and fecal survey samples in Southern China. METHODS: One hundred seventy and 74 carbapenem-resistant Acinetobacter were isolated from clinical infection samples and fecal survey samples, respectively. We detected the related genes, including carbapenemase genes (blaKPC, blaIMP, blaSPM, blaVIM, blaNDM, blaOXA-23-like, blaOXA-24/40-like, blaOXA-51-like, and blaOXA-58-like), colistin resistance-related genes (mcr-1, mcr-2, mcr-3, mcr-4, and mcr-5), a porin gene (carO), efflux pump genes (adeA, adeB, adeC, adeI, adeJ, and adeK), mobile genetic element genes (intI1, intI2, intI3, tnpU, tnp513, IS26, ISAba1, and ISAba125), and the integron variable region. Genotyping was analyzed by enterobacterial repetitive intergenic consensus (ERIC)-PCR and dendrogram cluster analysis. RESULTS: Among the 244 carbapenem-resistant Acinetobacter, the common carbapenemase-positive genes included the following: blaOXA-51-like, 183 (75.00%); blaOXA-23-like, 174 (71.30%); blaNDM-1, 57 (23.40%); and blaOXA-58-like, 30 (12.30%). The coexistence of mcr-1 and blaNDM-1 in five strains of A. junii was found for the first time. Eleven distinct carO gene variants were detected in 164 (67.20%) strains, and ten novel variants, which shared 92-99% identity with sequences in the Genbank database, were first reported. Efflux system genes were present in approximately 70% of the isolates; adeABC and adeIJK were observed in 76.23 and 72.13%, respectively. Class 1 integrons were detected in 180 (73.80%) strains and revealed that four gene cassette arrays contained 11 distinct genes. The genotyping by ERIC-PCR demonstrated a high genetic diversity of non-baumannii Acinetobacter, and greater than 90% similarity to A. baumannii. CONCLUSIONS: The blaNDM-1 gene was identified in up to 77% of the carbapenem-resistant Acinetobacter isolated from fecal survey samples, indicating that the gut might be a reservoir of resistant opportunistic bacteria. Intestinal bacteria can be transmitted through the fecal-hand, which is a clinical threat, thus, the monitoring of carbapenem-resistant bacteria from inpatients' feces should be improved, especially for patients who have been using antibiotics for a long time.


Assuntos
Infecções por Acinetobacter/tratamento farmacológico , Acinetobacter baumannii/genética , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Carbapenêmicos/efeitos adversos , Carbapenêmicos/uso terapêutico , Farmacorresistência Bacteriana/genética , Acinetobacter baumannii/isolamento & purificação , Proteínas de Bactérias/genética , China , Colistina/efeitos adversos , Colistina/uso terapêutico , Doenças Transmissíveis/tratamento farmacológico , Fezes/microbiologia , Variação Genética , Genótipo , Humanos , Integrons/genética , Testes de Sensibilidade Microbiana , Reação em Cadeia da Polimerase/métodos , Análise de Sequência de DNA , beta-Lactamases/genética
11.
Pan Afr Med J ; 33: 146, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31558943

RESUMO

Introduction: Infection due to multidrug-resistant microorganisms is a growing threat in healthcare settings. Acinetobacter species specifically A. baumannii is increasingly becoming resistant to most antimicrobial agents recommended for treatment. This study aimed to determine the antimicrobial susceptibility pattern of Acinetobacter species isolated from patients in Kenyatta National Hospital. Methods: We conducted a retrospective study based on VITEK 2 (BioMérieux) electronic records capturing identification and antimicrobial susceptibility of Acinetobacter isolates from patient samples analyzed between 2013 and 2015 at Kenyatta National Hospital microbiology laboratory. Generated data were analyzed using WHONET and SPSS. Results: A total of 590 Acinetobacter isolates were analyzed. 85% of the isolates tested were multi-drug resistant (MDR). Among the 590 isolates, 273 (46%) were from tracheal aspirates and 285 (48%) from the critical care unit. A. baumannii was the most frequently isolated species with high susceptibility to amikacin (77%) and poor susceptibility to ciprofloxacin (69-76%), tobramycin (37%) and meropenem (27%). Both A. lwoffii and A. haemolyticus had high susceptibility to amikacin (80-100%) and meropenem (75-100%). Conclusion: A. baumannii is resistant to commonly administered antibiotics. There is need for continuous antimicrobial resistance surveillance especially in health care facilities and strengthening of antibiotic stewardship programmes which will contribute to enhancement of infection control policies.


Assuntos
Infecções por Acinetobacter/tratamento farmacológico , Acinetobacter/efeitos dos fármacos , Antibacterianos/farmacologia , Acinetobacter/isolamento & purificação , Infecções por Acinetobacter/epidemiologia , Infecções por Acinetobacter/microbiologia , Farmacorresistência Bacteriana Múltipla , Feminino , Hospitais , Humanos , Quênia , Masculino , Testes de Sensibilidade Microbiana , Estudos Retrospectivos
12.
Molecules ; 24(15)2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31382389

RESUMO

Acinetobacter baumannii bacteremia represents a serious and increasing clinical problem due to the high mortality and treatment failures because of high rates of antibiotic resistance. Any additional new therapies for A. baumannii bacteremia would address a growing unmet medical need. ARV-1502 (designated as Chex1-Arg20 or A3-APO monomer in prior publications) is a designer proline-rich antimicrobial peptide chaperone protein inhibitor derived from insects and has demonstrated potent activity against multi-drug resistant (MDR) Gram-negative bacteria. In the current studies, we investigated the therapeutic efficacy of ARV-1502 administered intravenously (iv) alone and in combination with imipenem/cilastatin (IPM/CIL) in a mouse bacteremia model due to a MDR clinical A. baumannii strain, HUMC1. All ARV-1502 regimens (1.25, 2.5 and 5.0 mg/kg) significantly reduced bacterial density in the target tissues in a dose-dependent manner, as compared to the untreated control and IPM/CIL monotherapy (40 mg/kg) groups in the model. In addition, ARV-1502 treatment, even at the lowest dose, significantly improved survival vs. the control and IPM alone groups. As expected, IMP/CIL monotherapy had no therapeutic efficacy in the model, since the HUMC1 strain was resistant to IMP in vitro. However, the combination of ARV-1502 and IPM/CIL significantly enhanced the efficacy of ARV-1502, except the lowest dose of ARV-1502. The superior efficacy of ARV-1502 in the bacteremia model caused by MDR A. baumannii provides further support for studying this compound in severe infections caused by other MDR Gram-positive and -negative pathogens.


Assuntos
Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Bacteriemia/microbiologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Infecções por Acinetobacter/tratamento farmacológico , Acinetobacter baumannii/genética , Animais , Antibacterianos/química , Antibacterianos/uso terapêutico , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Modelos Animais de Doenças , Camundongos , Testes de Sensibilidade Microbiana
13.
Artigo em Inglês | MEDLINE | ID: mdl-31281799

RESUMO

Nosocomial infections have become alarming with the increase of multidrug-resistant bacterial strains of Acinetobacter baumannii. Being the causative agent in ~80% of the cases, these pathogenic gram-negative species could be deadly for hospitalized patients, especially in intensive care units utilizing ventilators, urinary catheters, and nasogastric tubes. Primarily infecting an immuno-compromised system, they are resistant to most antibiotics and are the root cause of various types of opportunistic infections including but not limited to septicemia, endocarditis, meningitis, pneumonia, skin, and wound sepsis and even urinary tract infections. Conventional experimental methods including typing, computational methods encompassing comparative genomics, and combined methods of reverse vaccinology and proteomics had been proposed to differentiate and develop vaccines and/or drugs for several outbreak strains. However, identifying proteins suitable enough to be posed as drug targets and/or molecular vaccines against the multidrug-resistant pathogenic bacterial strains has probably remained an open issue to address. In these cases of novel protein identification, the targets either are uncharacterized or have been unable to confer the most coveted protection either in the form of molecular vaccine candidates or as drug targets. Here, we report a strategic approach with the 3,766 proteins from the whole genome of A. baumannii ATCC19606 (AB) to rationally identify plausible candidates and propose them as future molecular vaccine candidates and/or drug targets. Essentially, we started with mapping the vaccine candidates (VaC) and virulence factors (ViF) of A. baumannii strain AYE onto strain ATCC19606 to identify them in the latter. We move on to build small networks of VaC and ViF to conceptualize their position in the network space of the whole genomic protein interactome (GPIN) and rationalize their candidature for drugs and/or molecular vaccines. To this end, we propose new sets of known proteins unearthed from interactome built using key factors, KeF, potent enough to compete with VaC and ViF. Our method is the first of its kind to propose, albeit theoretically, a rational approach to identify crucial proteins and pose them for candidates of vaccines and/or drugs effective enough to combat the deadly pathogenic threats of A. baumannii.


Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacologia , Vacinas Bacterianas/uso terapêutico , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Vacinas Sintéticas/farmacologia , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/imunologia , Infecções por Acinetobacter/microbiologia , Infecções por Acinetobacter/prevenção & controle , Acinetobacter baumannii/genética , Proteínas de Bactérias/genética , Biologia Computacional , Infecção Hospitalar , Genoma Bacteriano , Genômica , Humanos , Mapas de Interação de Proteínas/efeitos dos fármacos , Mapas de Interação de Proteínas/genética , Proteômica , Fatores de Virulência/genética
14.
J Pak Med Assoc ; 69(7): 981-984, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31308567

RESUMO

OBJECTIVE: To determine the prevalence of resistant pathogens and their antimicrobial susceptibility pattern in an intensive care unit. METHODS: The cross-sectional observational study was conducted at Foundation Hospital, Rawalpindi, Pakistan, from May to September 2016, and comprised tracheal tubes which were collected in sputum culture bottles from patients with clinical findings of ventilator associated pneumonia. The tubes were cultured to locate the resistant pathogens. RESULTS: A total of 113 different strains of bacteria were isolated from 80 patients. The main isolated bacteria was acinetobacter baumannii 45(39.8%) followed by klebsiella pneumonia 14(12.3%) and methicillin-resistant staphylococcus aureus 13(11.5%). Polymyxin B was the most appropriate drug for treating patients infected with acinetobacter baumannii with a sensitivity of 64% while vancomycin and linez oli dhad 100% sensitivity for methicill in - resistant staphylococcusaureus. CONCLUSIONS: Acinetobacter baumannii was the most prevalent strain in tracheal tubes and polymyxin B was the most effective medicine.


Assuntos
Infecções por Acinetobacter/microbiologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Infecções por Klebsiella/microbiologia , Pneumonia Associada à Ventilação Mecânica/microbiologia , Infecções Estafilocócicas/microbiologia , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/epidemiologia , Acinetobacter baumannii/isolamento & purificação , Biofilmes , Estudos Transversais , Humanos , Unidades de Terapia Intensiva , Intubação Intratraqueal/instrumentação , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae/isolamento & purificação , Linezolida/uso terapêutico , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Paquistão/epidemiologia , Pneumonia Associada à Ventilação Mecânica/epidemiologia , Polimixina B/uso terapêutico , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/epidemiologia , Infecções por Pseudomonas/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/epidemiologia , Vancomicina/uso terapêutico
15.
Clin Lab ; 65(7)2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31307186

RESUMO

BACKGROUND: Acinetobacter baumannii (A. baumannii) is an opportunistic pathogen associated with serious hospital acquired infections. It is resistant to multiple antibiotics. The therapy for infections due to this bacterium is a combination of aminoglycosides with carbapenem antibiotics. There are recent reports of the prevalence of ami-noglycoside resistance among A. baumannii. The aim of the present study was to determine the prevalence of phosphotransferases APH (3')-Via (aphA6), acetyltransferases AAC (3)-Ia (aacC1), nucleotidyl transferases ANT (2'')-Ia (aadB), and ANT (3") -Ia (aadA1) genes among clinical isolates of A. baumannii and its relation to resis-tance to amikacin and gentamicin. METHODS: The study included all clinical samples from intensive care units (ICUs) patients with suspected hospital acquired infections. Positive cultures were identified by Gram stain and complete biochemical identifications. An-tibiotic susceptibility was carried out by disc diffusion method. Minimum inhibitory concentration determination (MIC) to amikacin and gentamicin was performed by microdilution method. Polymerase chain reaction (PCR) was performed for detection of aadB, aadA1, aphA6, aadC1 genes. RESULTS: The study included 1,200 bacterial isolates from patients admitted to ICUs during the period of the study. A. baumannii represented 100 isolates from Gram negative bacilli. The study of MIC of A. baumannii to amikacin and gentamicin revealed that 50 (50%) of the isolates had resistance by MIC study with 36 (72%) of those having high level aminoglycoside resistance (HLAR) and 14 (28%) had non-high-level aminoglycoside resistance. The most common prevalent resistant genes among A. baumannii resistance to aminoglycosides was aadB (42%), fol-lowed by aphA6 (26%). Less prevalent genes were aadA1 (18%) and aacC1 (12%). There were 24 isolates with negative PCR for the studied genes. In a comparison between the prevalence of resistant genes among A. baumannii with HLAR and non HLAR, there was a non-significant increase of aphA6 (30.6%) and aadB (44.4%) in HLAR isolates compared to non HLAR (14.3%, 35.7%, respectively; p = 0.2), with a significant increase in aacC1 28.6% in HLAR compared to 5.6% in non HLAR (p = 0.02). CONCLUSIONS: Half of the clinical isolates of A. baumannii have resistance to the aminoglycosides amikacin and gen-tamicin. Most isolates have a high resistance level to aminoglycosides. The isolates have different types of amino-glycoside modifying genes. Further studies are required to detect other genes associated with resistance to amino-glycosides.


Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Aminoglicosídeos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Genes Bacterianos/genética , Acetiltransferases/genética , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/genética , Acinetobacter baumannii/fisiologia , Amicacina/farmacologia , Antibacterianos/farmacologia , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Estudos Transversais , Gentamicinas/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Nucleotidiltransferases/genética , Fosfotransferases/genética
16.
Medicine (Baltimore) ; 98(26): e16248, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261589

RESUMO

INTRODUCTION: Community-acquired (CA) carbapenem-susceptible Acinetobacter baumannii (CSAB) enterogenic sepsis is very rare but has a high mortality. Although CA A. baumannii bloodstream infections have been known to develop from respiratory tract, urinary tract, and intravenous device-related infections, CA A. baumannii bloodstream infections from the gastrointestinal tract have not yet been reported. PATIENT CONCERNS: A 73-year-old male with the chief presentation of gastrointestinal symptoms was initially diagnosed with acute gastroenteritis and showed poor clinical response to empirical antibiotic therapy. DIAGNOSES: The diagnosis of CSAB enterogenic sepsis was established based on results of blood culture, elevated serum procalcitonin level, and specific hemodynamic changes related to septic shock. INTERVENTIONS: The patient initially received empirical antibiotic treatment (cefodizime 2.0 q12 hours plus moxifloxacin 0.4 qd); then, treatment was changed to the conventional dose of carbapenem (imipenem 0.5 q6 hour). OUTCOMES: Finally, CSAB was eliminated from the bloodstream, and the patient was discharged. LESSONS: Although severe, CA CSAB enterogenic sepsis is often misdiagnosed because of its clinical rarity. Early diagnosis and appropriate initial empirical antibiotic therapy are crucial for treating such cases.


Assuntos
Infecções por Acinetobacter/diagnóstico , Acinetobacter baumannii/efeitos dos fármacos , Carbapenêmicos/farmacologia , Sepse/diagnóstico , Infecções por Acinetobacter/tratamento farmacológico , Idoso , Carbapenêmicos/uso terapêutico , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Humanos , Enteropatias/diagnóstico , Enteropatias/tratamento farmacológico , Enteropatias/microbiologia , Masculino , Testes de Sensibilidade Microbiana , Sepse/tratamento farmacológico
17.
EBioMedicine ; 46: 193-201, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31353294

RESUMO

BACKGROUND: Multidrug-resistant (MDR) Acinetobacter baumannii infections have high mortality rates and few treatment options. Synergistic drug combinations may improve clinical outcome and reduce further emergence of resistance in MDR pathogens. Here we show an unexpected potent synergy of two translation inhibitors against the pathogen: commonly prescribed macrolide antibiotic azithromycin (AZM), widely ignored as a treatment alternative for invasive Gram-negative pathogens, and minocycline, among the current standard-of-care agents used for A. baumannii. METHODS: Media-dependent activities of AZM and MIN were evaluated in minimum inhibitory concentration assays and kinetic killing curves, alone or in combination, both in standard bacteriologic media (cation-adjusted Mueller-Hinton Broth) and more physiologic tissue culture media (RPMI), with variations of bicarbonate as a physiologic buffer. Synergy was calculated by fractional inhibitory concentration index (FICI). Therapeutic benefit of combining AZM and MIN was tested in a murine model of A. baumannii pneumonia. AZM + MIN synergism was probed mechanistically by bacterial cytological profiling (BCP), a quantitative fluorescence microscopy technique that identifies disrupted bacterial cellular pathways on a single cell level, and real-time kinetic measurement of translation inhibition via quantitative luminescence. AZM + MIN synergism was further evaluated vs. other contemporary high priority MDR bacterial pathogens. FINDINGS: Although two translation inhibitors are not expected to synergize, each drug complemented kinetic deficiencies of the other, speeding the initiation and extending the duration of translation inhibition as verified by FICI, BCP and kinetic luminescence markers. In an MDR A. baumannii pneumonia model, AZM + MIN combination therapy decreased lung bacterial burden and enhanced survival rates. Synergy between AZM and MIN was also detected vs. MDR strains of Gram-negative Klebsiella pneumoniae and Pseudomonas aeruginosa, and the leading Gram-positive pathogen methicillin-resistant Staphylococcus aureus. INTERPRETATION: As both agents are FDA approved with excellent safety profiles, clinical investigation of AZM and MIN combination regimens may immediately be contemplated for optimal treatment of A. baumannii and other MDR bacterial infections in humans. FUND: National Institutes of Health U01 AI124326 (JP, GS, VN) and U54 HD090259 (GS, VN). IC was supported by the UCSD Research Training Program for Veterinarians T32 OD017863.


Assuntos
Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/mortalidade , Acinetobacter baumannii/genética , Animais , Azitromicina/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Camundongos , Testes de Sensibilidade Microbiana , Biossíntese de Proteínas/efeitos dos fármacos
18.
Rev Soc Bras Med Trop ; 52: e20180348, 2019 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-31271614

RESUMO

We report the occurrence in Brazil of the bla NDM-1 gene in Acinetobacter pittii, prior to the previously described first reports regarding the species Providencia rettgeri and Enterobacter hormaechei. Clinical isolates were investigated by polymerase chain reaction followed by bidirectional sequencing, and species was confirmed by 16S rDNA sequencing and matrix-assisted laser desorption-ionization time-of-flight spectrometry. A. pittii carrying bla NDM-1 was confirmed in a patient with no national or international travel history, or transfer from another hospital. The findings warn of the possibility of silent spread of bla NDM-1 to the community.


Assuntos
Infecções por Acinetobacter/microbiologia , Acinetobacter/isolamento & purificação , Antibacterianos/uso terapêutico , beta-Lactamases/isolamento & purificação , Infecções por Acinetobacter/tratamento farmacológico , Idoso de 80 Anos ou mais , Brasil , Feminino , Humanos , Testes de Sensibilidade Microbiana , beta-Lactamases/genética
19.
Microb Drug Resist ; 25(7): 1023-1031, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31335270

RESUMO

Acinetobacter calcoaceticus-baumannii complex isolates have been frequently associated with hospital and community infections, with A. baumannii being the most common. Other Acinetobacter spp. not belonging to this complex also cause infections in hospital settings, and the incidence has increased over the past few years. Some species of the Acinetobacter genus possess a great diversity of antibiotic resistance mechanisms, such as efflux pumps, porins, and resistance genes that can be acquired and disseminated by mobilizable genetic elements. By means of whole-genome sequencing, we describe in the clinical Acinetobacter haemolyticus strain AN54 different mechanisms of resistance that involve blaOXA-265, blaNDM-1, aphA6, aac(6')-Ig, and a resistance-nodulation-cell division-type efflux pump. This strain carries six plasmids, of which the plasmid pAhaeAN54e contains blaNDM-1 in a Tn125-like transposon that is truncated at the 3' end. This strain also has an insertion sequence IS91 and seven genes encoding hypothetical proteins. The pAhaeAN54e plasmid is nontypable and different from other plasmids carrying blaNDM-1 that have been reported in Mexico and other countries. The presence of these kinds of plasmids in an opportunistic pathogen such as A. haemolyticus highlights the role that these plasmids play in the dissemination of antibiotic resistance genes, especially against carbapenems, in Mexican hospitals.


Assuntos
Infecções por Acinetobacter/microbiologia , Acinetobacter/genética , Farmacorresistência Bacteriana/genética , Plasmídeos/genética , beta-Lactamases/genética , Acinetobacter/efeitos dos fármacos , Infecções por Acinetobacter/tratamento farmacológico , Animais , Antibacterianos/uso terapêutico , Carbapenêmicos/uso terapêutico , Criança , Elementos de DNA Transponíveis/genética , Farmacorresistência Bacteriana/efeitos dos fármacos , Humanos , Masculino , México , Testes de Sensibilidade Microbiana/métodos , Sequenciamento Completo do Genoma/métodos
20.
Microb Drug Resist ; 25(8): 1199-1203, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31158046

RESUMO

Aims: The aim of the study was to analyze the epidemiology of Acinetobacter baumannii and investigate the genetic characteristics of carbapenem-resistant A. baumannii (CRAB) isolates isolated from blood cultures in a regional hospital in Hong Kong. Results: Twenty blood culture isolates were collected from a regional hospital in Hong Kong from 2014 to 2017. Twenty isolates were grouped into five existing sequence types (STs) and five new STs within the following prevalence: ST195 was predominant with a prevalence of 45% (n = 9), followed by ST373 and ST447 (10%; n = 2 each), and ST176 and ST345 (5%; n = 1 each). Resistance to carbapenem antibiotics was 55% (n = 11). Six carbapenem-resistant isolates harbored blaOXA-23 genes and ISAba1 mobile elements. Polymerase chain reaction confirmed that ISAba1 is located upstream to the blaOXA-23 genes, suggesting an association between ISAba1 and blaOXA-23 genes with carbapenem resistance. Conclusion: This study is the first to report the emergence of CRAB ST195 harboring blaOXA-23 in Hong Kong.


Assuntos
Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/genética , Acinetobacter baumannii/isolamento & purificação , Proteínas de Bactérias/genética , Carbapenêmicos/uso terapêutico , Farmacorresistência Bacteriana/genética , beta-Lactamases/genética , Infecções por Acinetobacter/tratamento farmacológico , Antibacterianos/uso terapêutico , Bacteriemia/microbiologia , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Estudos Transversais , Hong Kong , Hospitais , Humanos , Testes de Sensibilidade Microbiana/métodos , Epidemiologia Molecular , Tipagem de Sequências Multilocus/métodos , Estudos Retrospectivos
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