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1.
BMC Microbiol ; 20(1): 314, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33076838

RESUMO

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) belong to diverse genetic backgrounds that differ in antibiotic resistance. Knowledge of the local clonal composition of MRSA strains is important for patients' management and for designing effective control and eradication methods. The aim of this study was to compare the antibiotic resistance patterns and genotypic characteristics of MRSA isolates obtained in public hospitals in Kuwait in 2016 and 2017 for changes in their resistance patterns and clonal composition. METHODS: A total of 4726 MRSA isolates obtained in 2016-2017 from clinical specimens in Kuwait public hospitals were characterized using antibiogram, SCCmec typing, spa typing and DNA microarray. RESULTS: The isolates expressed resistance to fusidic acid (52.9%), kanamycin (41.6%), gentamicin (32.5%) and erythromycin (36.2%). The prevalence of high-level mupirocin resistance decreased from 3.7% in 2016 to 2.4% in 2017, while the proportion of resistance to other antibiotics remained relatively stable. A total of 382 spa types were detected with eight spa types, t688 (N = 547), t304 (N = 428), t860 (N = 394), t127 (N = 306), t044 (N = 230), t311 (N = 243), t223 (N = 184) and t002 (N = 181) constituting 53.1% of the MRSA isolates in 2016-2017. Of the 3004 MRSA isolates obtained in 2016 (N = 1327) and 2017 (N = 1677) selected for DNA microarray analysis, 26 clonal complexes (CCs) were identified. Most of the isolates belonged to CC1 (N = 248), CC5 (N = 833), CC6 (N = 241), CC8 (N = 292), CC22 (N = 421), CC30 (N = 177), CC80 (N = 177) and CC97 (N = 171). The prevalence of CC5 isolates has significantly (p ≤ 0.05) increased from 294 isolates in 2016 to 539 isolates in 2017. Although CC22 increased from 196 isolates in 2016 to 225 isolates in 2017, CC1 increased from 112 isolates in 2016 to 136 isolates in 2017, CC6 increased from 103 isolates in 2016 to 138 isolates in 2017, these changes were not significant (p ≥ 0.05). CONCLUSION: These results revealed the diversity in the genetic backgrounds of MRSA isolates and the stable maintenance of the dominant MRSA clones in Kuwait hospitals in 2016 and 2017 suggesting an on-going transmission of these clones. Novel and creative infection prevention and control measures are required to curtail further transmission.

2.
PLoS One ; 15(8): e0236713, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32750089

RESUMO

Coagulase-negative staphylococci (CoNS) are the most common isolates from blood culture in neonates resulting in high mortality and morbidity. This study investigated CoNS obtained from blood cultures of neonates for antibiotic resistance and virulence factors, and possible association with inflammatory response (C-reactive protein). A total of 93 CoNS isolates were collected from 76 blood cultures of neonates at the Maternity hospital in Kuwait in a six-month period and investigated for susceptibility to antibiotics, carriage of staphylococcal cassette chromosome mec (SCCmec), and virulence-associated genes. The 93 CoNS isolates consisted of S. epidermidis (76; 81.7%), S. capitis (12; 12.9%), S. hominis (2; 2.1%), S. warneri (2; 2.1%) and S. haemolyticus (1; 1.0%). Eighty-six (92.4%) of the isolates were resistant to cefoxitin (MR-CoNS) while 49 (52.7%) expressed multi-antibiotic resistance. The methicillin-resistant isolates (MR-CoNS) carried SCCmec III, SCCmec IVa and four combinations of SCCmec types including SCCmec types I+IVa (one S. warneri and 25 S. epidermidis isolates), types I+III (one S. epidermidis isolate), types III+IVa (six S. epidermidis isolates) and types I+III+IVa (one S. epidermidis isolate). The most common virulence-related genes were icaC, seb, arc detected in 69.7%, 60.5%, 40.8% of the isolates respectively. Two isolates were positive for tst1. No association between C-reactive protein and antibiotic resistance or virulence factors was established. This study revealed that S. epidermidis carrying different SCCmec genetic elements, was the dominant CoNS species isolated from neonatal blood cultures with 90.3% and 36.6% of the isolates positive for genes for biofilm and ACME production respectively.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Recém-Nascido Prematuro , Infecções Estafilocócicas/microbiologia , Staphylococcus/efeitos dos fármacos , Toxinas Bacterianas/genética , Biofilmes , Coagulase/metabolismo , Feminino , Genes Bacterianos , Humanos , Recém-Nascido , Kuweit , Masculino , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Staphylococcus/enzimologia , Staphylococcus/isolamento & purificação , Staphylococcus/metabolismo , Fatores de Virulência/genética , Fatores de Virulência/metabolismo
3.
Infect Drug Resist ; 13: 617-626, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32110072

RESUMO

Purpose: Methicillin-resistant S. aureus (MRSA) belonging to clonal complex 15 (CC15-MRSA) is rare among clinical isolates with few reports from retail camel meat and human patients. This study investigated the genetic relatedness of CC15-MRSA isolated for the first time from patients in Kuwait hospitals. Methods: Antibiotic susceptibility was tested by the disk diffusion method. Minimum inhibitory concentration was determined using Etest strips. Molecular typing was performed using spa tying, multilocus sequence tying and DNA microarray. Results: Of 1327 MRSA isolates, 42 (3.1%) were identified as CC15-MRSA. The 42 isolates belonged to sequence type ST1535-harbored SCCmec type V and spa types t084 (36 isolates), t346 (3 isolates) and one of t114, t228 and t7583. All 42 isolates were resistant to gentamicin, kanamycin, fusidic acid and cadmium acetate; 38 isolates were resistant to tetracycline. The isolates harbored aacA-aphD and fusC that codes for gentamicin and fusidic acid resistance, respectively. Tet(K) was present in the tetracycline-resistant isolates. In addition, the 42 isolates carried inu(A) (lincosamide nucleotidyltransferase) that confers resistance to lincomycin and clindamycin although phenotypically susceptible to these antibiotics. The isolates belonged to accessory gene regulator type II and capsular polysaccharide group 8 but lacked genes for Staphylococcus enterotoxins, toxic shock syndrome toxin, collagen-binding adhesins and Panton-Valentine leukocidin. Conclusion: This study revealed the emergence and transmission of a previously rare MRSA clone among human patients in Kuwait hospitals and highlights the increasing infiltration of rare MRSA into the human population.

4.
Sci Rep ; 9(1): 18527, 2019 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-31811246

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) are a major cause of healthcare and community- associated infections due to their ability to express a variety of virulence factors. We investigated 209 MRSA isolates obtained from 1 January to 31 December 2016 using a combination of phenotypic and genotypic methods to understand the genetic backgrounds of MRSA strains obtained in a General hospital in Kuwait. Antibiotics susceptibility was performed with disk diffusion, and MIC was measured with Etest strips. Molecular typing was performed using SCCmec typing, spa typing, and DNA microarray for antibiotic resistance and virulence genes. The isolates were susceptible to vancomycin, teicoplanin, rifampicin, ceftaroline, and linezolid but were resistant to gentamicin, tetracycline, erythromycin, fusidic acid, chloramphenicol and ciprofloxacin. Molecular typing revealed six SCCmec types, 56 spa types and 16 clonal complexes (CC). The common SCCmec types were type IV (39.5%), type III (34.4%), type V (25.8%) and type VI (3.8%). The dominant spa types were t860 (23.9%), t945 (8.6%), t127 (6.7%), t688 (6.7%), t304 (6.2) and t044 (5.7%). The other spa types occurred sporadically. Genes for PVL was detected in 59 (28.2%) of the isolates. CC8-ST239-MRSA-III + SCCmer (23.3%) was the most prevalent clone, followed by CC6-MRSA-IV (8.3%), CC80-MRSA-IV [PVL+] (5.8%), CC5-MRSA-VI + SCCfus (5.0%), CC30-MRSA-IV[PVL+] (4.1%), CC1-MRSA-V + SCCfus [PVL+] (4.1%), CC5-MRSA-V + SCCfus (4.1%) and CC22-MRSA-IV[PVL+] (4.1%). The study revealed that despite the emergence of MRSA with diverse genetic backgrounds over the years, ST239-MRSA-III remained the dominant clone in the hospital. This warrants reassessment of infection prevention and control procedures at this hospital.


Assuntos
Infecções Comunitárias Adquiridas/microbiologia , Infecção Hospitalar/microbiologia , Staphylococcus aureus Resistente à Meticilina/genética , Meticilina/farmacologia , Infecções Estafilocócicas/microbiologia , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/epidemiologia , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/epidemiologia , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , Farmacorresistência Bacteriana Múltipla/genética , Feminino , Humanos , Kuweit/epidemiologia , Masculino , Meticilina/uso terapêutico , Resistência a Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Testes de Sensibilidade Microbiana , Epidemiologia Molecular , Tipagem Molecular , Análise de Sequência com Séries de Oligonucleotídeos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/epidemiologia , Centros de Atenção Terciária/estatística & dados numéricos , Fatores de Virulência/genética , Fatores de Virulência/isolamento & purificação
5.
Front Microbiol ; 10: 2912, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31969864

RESUMO

Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) has been reported to colonize and cause infections in animals as well as in humans. LA-MRSA isolates have only recently been identified in patients admitted to Kuwait hospitals. This study was conducted to characterize LA-MRSA isolates obtained from patients admitted to Kuwait hospitals. A total of 202 (7.1%) of 2,823 MRSA isolates obtained from clinical samples in 2016 and 2017 in 11 public Kuwait hospitals were assigned to lineages previously known to be associated with livestock. They were characterized using antibiogram, spa typing, and DNA microarray for the assignment of clonal complexes (CCs) and detection of antibiotic resistance and virulence determinants. Identification as putative LA-MRSA clones was based on the molecular definition inferred from DNA microarray. The LA-MRSA isolates consisted of CC96 (N = 31), CC97 (N = 169), and CC398 (N = 2). Isolates belonging to CC96 and CC398 were resistant to erythromycin and clindamycin mediated by erm(A) and erm(C). CC97 isolates were multiresistant to gentamicin, kanamycin, erythromycin, clindamycin, tetracycline, chloramphenicol, fusidic acid, trimethoprim, and ciprofloxacin and harbored aacA-aphD, erm(A), erm(C), msr(A), tet(K), cat, fusC, and dfrS1. In total, 35 spa types were identified among the isolates. CC398 isolates consisted of t899 and t034. Ten spa types were identified among CC96 with t11822 (N = 13) as the most prevalent. CC97 consisted of 26 spa types with most belonging to t267 (N = 73) followed by t359 (N = 39). CC398 was composed of CC398-MRSA-IV and CC398-MRSA-V (PVL+). CC96 belonged to CC96-MRSA-IV and CC96-MRSA-IV (PVL+) Central Asian caMRSA/WA MRSA-119. CC97 consisted of six strains including CC97-MRSA-V (fusC +), CC97-MRSA-IV WA MRSA-54/63, CC97-MRSA-V, CC97-MRSA-(V+fus), CC97-MRSA-(mec VI+fus), and CC97-MRSA (mecV/VT+fus+ccrAB2). Whereas CC96 and CC97 isolates were identified in 2016 and 2017, CC398 isolates were detected only in 2016. This study identified four LA-MRSA clones among MRSA isolated from patients in Kuwait hospitals in 2016-2017 with CC97-MRSA-V (fusC +) as the dominant clone. The presence of LA-MRSA with different genetic backgrounds suggests its independent acquisition from different sources.

6.
Front Microbiol ; 9: 1436, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30087657

RESUMO

ST239-MRSA-III is probably the oldest truly pandemic MRSA strain, circulating in many countries since the 1970s. It is still frequently isolated in some parts of the world although it has been replaced by other MRSA strains in, e.g., most of Europe. Previous genotyping work (Harris et al., 2010; Castillo-Ramírez et al., 2012) suggested a split in geographically defined clades. In the present study, a collection of 184 ST239-MRSA-III isolates, mainly from countries not covered by the previous studies were characterized using two DNA microarrays (i) targeting an extensive range of typing markers, virulence and resistance genes and (ii) a SCCmec subtyping array. Thirty additional isolates underwent whole-genome sequencing (WGS) and, together with published WGS data for 215 ST239-MRSA-III isolates, were analyzed using in-silico analysis for comparison with the microarray data and with special regard to variation within SCCmec elements. This permitted the assignment of isolates and sequences to 39 different SCCmec III subtypes, and to three major and several minor clades. One clade, characterized by the integration of a transposon into nsaB and by the loss of fnbB and splE was detected among isolates from Turkey, Romania and other Eastern European countries, Russia, Pakistan, and (mainly Northern) China. Another clade, harboring sasX/sesI is widespread in South-East Asia including China/Hong Kong, and surprisingly also in Trinidad & Tobago. A third, related, but sasX/sesI-negative clade occurs not only in Latin America but also in Russia and in the Middle East from where it apparently originated and from where it also was transferred to Ireland. Minor clades exist or existed in Western Europe and Greece, in Portugal, in Australia and New Zealand as well as in the Middle East. Isolates from countries where this strain is not epidemic (such as Germany) frequently are associated with foreign travel and/or hospitalization abroad. The wide dissemination of this strain and the fact that it was able to cause a hospital-borne pandemic that lasted nearly 50 years emphasizes the need for stringent infection prevention and control and admission screening.

7.
PLoS One ; 13(4): e0195933, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29668723

RESUMO

BACKGROUND: Frequent changes in the epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) occurring worldwide demand regular surveillance to study their composition and distribution in healthcare facilities. We investigated the genotypic characteristics of MRSA obtained in Kuwait hospitals to better understand their clonal distribution. MATERIALS AND METHODS: A total of 1,327 MRSA isolates obtained from clinical samples in 13 Kuwait hospitals from 1 January to 31 December 2016 were investigated using antibiogram, SCCmec typing, spa typing and DNA microarray. RESULTS: The isolates belonged to six SCCmec types with the majority belonging to type IV (658; 49.5%) and type V (355; 26.7%). Two hundred and sixty-one spa types were identified with spa types t688, t304, t860, t127, t044, t311, t002, t223, t267, t019, t3841, t005, t084, t852, and t657 constituting 51.0% (n = 677) of the isolates. Among the 1,327 MRSA isolates, 102 (7.68%) isolates were identified as novel variants of internationally recognized MRSA clones. These 102 isolates were investigated further and belonged to 14 clonal complexes (CCs) with CC361 (32; 32.3%), CC30 (15; 14.7%), CC22 (13; 12.7%) and CC1 (11, 10.7%) as the dominant CCs. Eighty-one (79.4%) of the novel isolates harbored SCCmec IV or V+fusC composite genetic elements. Four isolates (3.9%) harbored unusual combinations of ccr and mec complexes comprising of CC6-MRSA [IV+fusC+ccrC], CC97-MRSA [V/VT+fusC+ccrAB2], CC121-MRSA [V/VT+fusC+ccrB4] and CC1-MRSA-pseudoSCCmec [class B mec+fusc+ccrAB1]. Forty-six (45.1%) of these isolates were positive for PVL and 89 (87.2%) were resistant to fusidic acid mediated by fusC. CONCLUSIONS: The study showed the emergence of novel variants of previously recognized MRSA genotypes with unusual genetic characteristics including high prevalence of PVL and fusidic acid resistance in Kuwait hospitals. This has added to the dynamic lists of known variations in MRSA genomes which can impose serious challenges for infection control and treatment of MRSA infections.


Assuntos
Infecção Hospitalar , Variação Genética , Genótipo , Staphylococcus aureus Resistente à Meticilina/classificação , Staphylococcus aureus Resistente à Meticilina/genética , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/microbiologia , Genes Bacterianos , Hospitais , Humanos , Kuweit/epidemiologia , Tipagem de Sequências Multilocus , Virulência/genética
8.
Med Princ Pract ; 26(5): 485-490, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28977793

RESUMO

OBJECTIVE: The aim of this study was to determine antibiotic resistance trends and carriage of staphylococcal cassette chromosome mec (SCCmec) genetic elements in methicillin-resistant Staphylococcus aureus (MRSA) isolated in Kuwait hospitals to ascertain whether they were healthcare associated (HA-MRSA) or community associated (CA-MRSA). MATERIALS AND METHODS: In total, 6,922 MRSA isolates obtained from different clinical samples were tested for resistance to antibiotics, urease production, and carriage of SCCmec elements. RESULTS: All MRSA isolates were susceptible to linezolid, vancomycin, and teicoplanin. However, some isolates were resistant to kanamycin (2,979; 43%), ciprofloxacin (2,955; 42.7%), erythromycin and clindamycin (2,935; 42.4%), fusidic acid (2,858; 41.2%), gentamicin (2,665; 38.5%), tetracycline (2,652; 38.3%), and trimethoprim (2,324; 33.5%). Whereas the prevalence of resistance to most antibiotics showed annual variations, those resistant to chloramphenicol and rifampicin increased from 2.6 and 0.1% to 9.6 and 1.6%, respectively, and high-level mupirocin resistance declined from 9.3% in 2011 to 3.6% in 2015. In total, 3,244 (53.9%) of the isolates carried SCCmec IV followed by SCCmec III (1,737; 28.8%) and SCCmec V (890; 14.8%). SCCmec I (21; 0.3%) and II (79; 0.8%) occurred sporadically. A total of 3,651 (60.7%) of the isolates belonged to the CA-MRSA genotype and 2,290 isolates (38.1%) were identified as HA-MRSA. CONCLUSION: This study demonstrates changes in antibiotic resistance patterns of MRSA over time and reinforces the value of surveillance in detecting such changes for the benefit of infection control and patient management.


Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Hospitais , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/genética , Proteínas de Ligação às Penicilinas/genética , Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana Múltipla/genética , Genótipo , Humanos , Kuweit , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana
9.
Front Microbiol ; 8: 1359, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28775716

RESUMO

The objective of this investigation was to identify the lineages of MRSA and MSSA with reduced susceptibility to chlorhexidine in Kuwaiti hospitals. 121 clinical MRSA and 56 MSSA isolates were included in this study. Antimicrobial susceptibility testing was performed for a selection of agents including chlorhexidine and resistance genes were amplified and sequenced. PFGE, spa typing, and MLST were completed for a selection of isolates. The results showed SCCmec II, III, IV, and V were present in 0.8, 21.5, 69.4, and 8.3% of the MRSA isolates. agr-1Sa was the most prevalent type in both MSSA (48%) and MRSA (54%). Forty-five percentage of MRSA contained pvl and 39% contained lukE-lukD, however, as many as 86% of MSSA contained pvl and 96.4% contained lukE-lukD. qac A-C genes were identified in 12.3% of MRSA, norA was present in 82.6% and blaZ in 94.2%. Among MSSA only 5.4% harbored qacA, 83% contained norA, and 91% blaZ. Multi-drug resistant ST239/t945 lineage containing a qac gene was the most identified S. aureus. However, other lineages, including ST772-MRSA-V/t4867/pvl(+)qacC/smr and non-qac harboring lineages of ST217-MRSAIV/t3244/pvl(-), ST34-MSSA/t161/pvl(+), ST5-MSSA/t688/pvl(+), ST5-MSSA/t4867/norA(+), and ST672-MSSA/t003/pvl(-), also showed reduced susceptibility to chlorhexidine. The observed reduced susceptibility of non-qac dependent MSSA isolates to chlorhexidine suggests the involvement of other elements in promoting higher MBC (≥30 mg/L). Our results confirm that monitoring MSSA is essential as they may have the potential to survive low level biocide exposure.

10.
PLoS One ; 12(6): e0179563, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28640870

RESUMO

BACKGROUND: Methicillin- resistant Staphylococcus aureus (MRSA) is a major pathogen causing healthcare- and community- acquired infections. The purpose of this study was to characterize MRSA isolated at the Maternity Hospital between 2006 and 2011 for their genetic relatedness. MATERIALS AND METHODS: The MRSA isolates were investigated using a combination of antibiogram, Staphylococcal chromosome cassette mec (SCCmec) and spa typing to determine their relatedness to MRSA isolated in other Kuwait hospitals. The isolates were also investigated for the carriage of genes for Pantone valentine Leukocidin (PVL). RESULTS: A total of 103 MRSA obtained from 64 neonates, 17 adult patients and 12 healthcare workers. The isolates were resistant to Kanamycin (46.6%), gentamicin (40.8%), trimethoprim (32%), ciprofloxacin (22.3%), fusidic acid (16.5%), tetracycline (19.4%), erythromycin (15.5%), clindamycin (15.5%), streptomycin (11.6%) high-level mupirocin (2.9%) and chloramphenicol (0.9%). Twenty (19.4%) of the isolates were multiresistant. Thirty-one (30.0%) isolates were positive for PVL. Molecular typing revealed the presence of 11 clonal complexes and 23 clones with ST5-V-t002, (N = 22), ST22-IV-t223 (N = 18), ST22-IV-t852 (N = 10), ST80-IV-t044 (N = 7), ST5-V-t688 (N = 5), ST772-V-t657 (N = 5) and ST239-III-t860 (N = 4) constituting 66.9% of the isolates. Other clones were isolated sporadically. The number of MRSA isolates increased from two in 2006 to 22 in 2011 with a peak of 43 in 2008. CONCLUSION: The study revealed a high prevalence of community-associated MRSA Maternity hospital. The MRSA population consisted of known strains, such as ST239-III-t680, ST22-IV-t223/t852 and ST80-IV-t044, that were reported previously in Kuwait and novel strains such as ST5-V-t002, and several sporadic strains obtained for the first time in the Maternity hospital. This study has provided an initial data which will serve as a platform for future comparative studies on the distribution of MRSA clones in the Maternity hospital in Kuwait.


Assuntos
Infecções Comunitárias Adquiridas/microbiologia , Maternidades , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Adulto , Antibacterianos/farmacologia , Humanos , Recém-Nascido , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/genética , Tipagem Molecular
11.
Microb Pathog ; 105: 1-7, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28179118

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) as a major cause of infection in health care, hospital and community settings is a global health concern. The purpose of this study was to determine the antibiotic susceptibility pattern and distribution of circulating molecular types of MRSA in a burn hospital in Tehran, the capital of Iran. During a 10-month study period, 106 Staphylococcus aureus isolates were assessed. Isolates were subjected to susceptibility testing using the disk diffusion method and Polymerase Chain Reaction (PCR) for detection of mecA, fem and nuc genes. The presence of PVL and tst encoding genes were determined by PCR method. All the MRSA isolates were genotyped by multilocus sequence typing (MLST), spa typing, SCCmec typing and agr typing. The presence of mecA gene was confirmed in all the Staphylococcus aureus isolates. Antimicrobial susceptibility testing revealed a high resistance rate (90.6%) to ampicillin, tetracycline, and erythromycin. The rates of resistance to remaining antibiotics tested varied between 18.9% and 84.9%. The high- level of resistance to mupirocin was confirmed in 19.8% of MRSA strains isolated from burn patients. Multi-drug resistance was observed in 90.6% of isolates. Sixteen of the 106 MRSA isolates (15.1%) harbored PVL-encoding genes. The majority of our MRSA strains carried SCCmec III (71.7%). ST239-SCCmec III/t037 (34%) was the most common genotype followed by ST239-SCCmec III/t030 (24.5%), ST15-SCCmec IV/t084 (15.1%), ST22-SCCmec IV/t790 (13.2%), and ST239-SCCmec III/t631 (13.2%). Mupirocin resistant MRSA isolates belonged to ST15-SCCmec IV/t084 (40%), ST22-SCCmec IV/t790 (23.3%), ST239-SCCmec III/t631 (20%), and ST239-SCCmec III/t030 (16.7%) clones. The results showed that genetically diverse strains of MRSA are circulating in our burn hospitals with relatively high prevalence of ST239-SCCmec III/t037 clone. The findings support the need for regular surveillance of MRSA to determine the distribution of existing MRSA clones and to detect the emergence of new MRSA clones.


Assuntos
Queimaduras/complicações , Variação Genética , Genótipo , Staphylococcus aureus Resistente à Meticilina/classificação , Staphylococcus aureus Resistente à Meticilina/genética , Infecções Cutâneas Estafilocócicas/microbiologia , Adolescente , Adulto , Antibacterianos/farmacologia , Criança , Pré-Escolar , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Feminino , Hospitais , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Pessoa de Meia-Idade , Epidemiologia Molecular , Tipagem Molecular , Reação em Cadeia da Polimerase , Infecções Cutâneas Estafilocócicas/epidemiologia , Fatores de Virulência/genética , Adulto Jovem
12.
PLoS One ; 11(9): e0162744, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27631623

RESUMO

BACKGROUND: As the epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) is constantly changing globally, determining the prevailing MRSA clones in a local healthcare facility is important for better management of infections. This study investigated clonal composition and distribution of MRSA isolates in Kuwait's hospitals using a combination of molecular typing methods. MATERIALS AND METHODS: In total, 400 non-repeat MRSA isolates were obtained between 1992 and 2010 in 13 public hospitals and were characterized using antibiogram, SCCmec typing, spa typing, and multilocus-sequence typing. Clonal assignment and detection of virulence factors and antibiotic resistance genes were performed by DNA microarray. RESULTS: The isolates were resistant to kanamycin (74.2%), erythromycin (69.5%), tetracycline (66.7%), gentamicin (61%), ciprofloxacin, (61%), fusidic acid (53.5%), clindamycin (41.5%), high-level mupirocin resistance (5.2%) and carried aphA3, aacA-aphD, ermA, ermC, mupA, tetK, tetM, fusC and far1. Molecular typing revealed 31 different MRSA clones consisting of ST239-MRSA-III (52.2%), ST22-MRSA-IV (9.2%), ST80-MRSA-IV (7.5%), ST5-MRSA-II/IV/V/VI (6.5%), ST30-MRSA-IV (3.5%), ST241-MRSA-III (2.7%), ST6-MRSA-IV (2.2%), ST36-MRSA-II (2%) and ST772-MRSA-V (1.75%). The isolates differed in the carriage of genes for enterotoxins, Panton-Valentine leukocidin (PVL), toxic shock syndrome toxin (tst-1), arginine catabolic mobile element (ACME) and exfoliative toxins. The number of clones increased from one (ST239-III-t037) in 1992 to 30 in 2010 including ST8-IV-t008 [PVL+] [ACME+] (USA300), ST772-V (Bengal Bay clone) and ST2816 identified for the first time in Kuwait. CONCLUSION: The study revealed that the MRSA isolates belonged to diverse clones that changed in numbers and diversity overtime. Although ST239-MRSA-III, a healthcare-associated clone remained the dominant MRSA clone overtime, the newly emerged clones consisted mostly of community-associated.


Assuntos
Hospitais , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Kuweit
13.
Int J Infect Dis ; 51: 31-35, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27578204

RESUMO

OBJECTIVES: CC22-MRSA-IV, UK-EMRSA-15/Barnim EMRSA, is a common and pandemic strain of methicillin-resistant Staphylococcus aureus (MRSA) that has been found mainly in Western Europe, but also in other parts of the world including some Gulf countries. One suspected case of an infection with this strain in a patient who was admitted to the surgical unit in Riyadh, Kingdom of Saudi Arabia (KSA) was investigated in order to check whether this strain has reached KSA. METHODS: Besides the index isolate, 46 additional isolates of CC22-MRSA-IV from patients from KSA, Abu Dhabi, Kuwait, and Germany (patients with a history of travel in the Middle East), were characterized by microarray hybridization. RESULTS: The study revealed a regional presence of as many as six distinct 'strains' of CC22-MRSA-IV that could be distinguished based on carriage of SCCmec IV subtypes and virulence factors. No true UK-EMRSA-15/Barnim EMRSA was identified in Riyadh; all suspected isolates from Riyadh were assigned to other, albeit related strains. However, this strain was identified in Abu Dhabi and Kuwait. CONCLUSIONS: CC22-MRSA-IV from KSA could be linked to other epidemic strains from the Middle East and possibly India, rather than to the Western European UK-EMRSA-15/Barnim EMRSA. High-resolution typing methods, including SCCmec subtyping, might help to differentiate related epidemic strains and to monitor routes of transmission.


Assuntos
Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções Estafilocócicas/microbiologia , Alemanha , Humanos , Índia , Kuweit , Masculino , Pessoa de Meia-Idade , Arábia Saudita/epidemiologia , Infecções Estafilocócicas/epidemiologia , Emirados Árabes Unidos , Fatores de Virulência
14.
PLoS One ; 11(5): e0155529, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27171373

RESUMO

INTRODUCTION: The emergence of methicillin-resistant Staphylococcus aureus (MRSA) in different patient populations is a major public health concern. This study determined the prevalence and distribution of circulating molecular types of MRSA in hospitalized patients in ICU of hospitals in Tehran. MATERIALS AND METHODS: A total of 70 MRSA isolates were collected from patients in eight hospitals. Antimicrobial resistance patterns were determined using the disk diffusion method. The presence of toxin encoding genes and the vancomycin resistance gene were determined by PCR. The MRSA isolates were further analyzed using multi-locus sequence, spa, SCCmec, and agr typing. RESULTS: The MRSA prevalence was 93.3%. Antimicrobial susceptibility testing revealed a high resistance rate (97.1%) to ampicillin and penicillin. The rate of resistance to the majority of antibiotics tested was 30% to 71.4%. Two isolates belonging to the ST22-SCCmec IV/t790 clone (MIC ≥ 8 µg/ml) had intermediate resistance to vancomycin. The majority of MRSA isolates (24.3%) were associated with the ST22-SCCmec IV/t790 clone; the other MRSA clones were ST859-SCCmec IV/t969 (18.6%), ST239-SCCmec III/t037 (17.1%), and ST291-SCCmec IV/t030 (8.6%). CONCLUSIONS: The circulating MRSA strains in Iranian hospitals were genetically diverse with a relatively high prevalence of the ST22-SCCmec IV/t790 clone. These findings support the need for future surveillance studies on MRSA to better elucidate the distribution of existing MRSA clones and detect emergence of new MRSA clones.


Assuntos
Unidades de Terapia Intensiva , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Adolescente , Adulto , Idoso , Anti-Infecciosos/farmacologia , Criança , Pré-Escolar , Células Clonais , Feminino , Humanos , Lactente , Irã (Geográfico)/epidemiologia , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/microbiologia
15.
Eur J Med Chem ; 106: 120-31, 2015 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-26536532

RESUMO

Research activities on the oxazolidinone antibacterial class of compounds continue to focus on developing newer derivatives with improved potency, broad-spectrum activity and safety profiles superior to linezolid. Among the safety concerns with the oxazolidinone antibacterial agents is inhibition of monoamine oxidases (MAO) resulting from their structural similarity with toloxatone, a known MAO inhibitor. Diverse substitution patterns at the C-5 position of the oxazolidinone ring have been shown to significantly affect both antibacterial activity and MAO inhibition to varying degrees. Also, the antibacterial activity of compounds containing iron-chelating functionalities, such as the hydroxamic acids, 8-hydroxyquinolines and catechols have been correlated to their ability to alter iron intake and/or metabolism. Hence a series of novel 5-(hydroxamic acid)methyl oxazolidinone derivatives were synthesized and evaluated for their antibacterial and MAO-A and -B inhibitory activities. The compounds were devoid of significant antibacterial activity but most demonstrated moderate MAO-A and -B inhibitory activities. Computer modeling studies revealed that the lack of potent antibacterial activity was due to significant steric interaction between the hydroxamic acid N-OH oxygen atom and one of the G2540 5'-phosphate oxygen atoms at the bacterial ribosomal binding site. Therefore, the replacement of the 5-acetamidomethyl group of linezolid with the 5-(N-hydroxyacetamido)methyl group present in the hydroxamic acid oxazolidinone derivatives was concluded to be detrimental to antibacterial activity. Furthermore, the 5-(hydroxamic acid)methyl oxazolidinone derivatives were also less active as MAO-A and -B inhibitors compared with linezolid and the selective inhibitors clorgyline and pargyline. In general, the 5-(hydroxamic acid)methyl oxazolidinone derivatives demonstrated moderate but selective MAO-B inhibitory activity.


Assuntos
Ácidos Hidroxâmicos/farmacologia , Inibidores da Monoaminoxidase/farmacologia , Monoaminoxidase/metabolismo , Oxazolidinonas/farmacologia , Relação Dose-Resposta a Droga , Humanos , Ácidos Hidroxâmicos/síntese química , Ácidos Hidroxâmicos/química , Modelos Moleculares , Estrutura Molecular , Inibidores da Monoaminoxidase/síntese química , Inibidores da Monoaminoxidase/química , Oxazolidinonas/síntese química , Oxazolidinonas/química , Relação Estrutura-Atividade
16.
Eur J Pharm Sci ; 71: 56-61, 2015 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-25701103

RESUMO

Oxazolidinone class of compounds continue to generate interest as promising agents effective against sensitive and resistant Gram-positive pathogenic bacteria strains. Recent focus is to develop new potent derivatives with improved broad-spectrum activity and safety profile superior to linezolid. An important toxicity issue for this class of compounds arises from the structural similarity with toloxatone, a known MAO inhibitor. Herein, we report the evaluation of a small series of 5-(1H-1,2,3-triazolyl)-, 5-(4-methyl-1H-1,2,3-triazolyl)-, 5-(5-methyl-1H-1,2,3-triazolyl)- and 5-imidazolyl-methyl oxazolidinone analogs with and without antibacterial activity for their effects as inhibitors of monoamine-A and -B (MAO-A and -B) oxidases. Substitutions at the oxazolidinone C-5 position significantly affected antibacterial activity and MAO inhibition. The N-substituted-glycinyl 1H-1,2,3-triazolyl methyl oxazolidinones with potent antibacterial activity demonstrated only weak to moderate affinity for MAO-A and -B, supporting further investigation for this group of compounds.


Assuntos
Antibacterianos/farmacologia , Inibidores da Monoaminoxidase/farmacologia , Monoaminoxidase/metabolismo , Oxazolidinonas/farmacologia
17.
mBio ; 5(5): e01044-14, 2014 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-25161186

RESUMO

UNLABELLED: Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) was recognized in Europe and worldwide in the late 1990s. Within a decade, several genetically and geographically distinct CA-MRSA lineages carrying the small SCCmec type IV and V genetic elements and the Panton-Valentine leukocidin (PVL) emerged around the world. In Europe, the predominant CA-MRSA strain belongs to clonal complex 80 (CC80) and is resistant to kanamycin/amikacin and fusidic acid. CC80 was first reported in 1993 but was relatively rare until the late 1990s. It has since been identified throughout North Africa, the Middle East, and Europe, with recent sporadic reports in sub-Saharan Africa. While strongly associated with skin and soft tissue infections, it is rarely found among asymptomatic carriers. Methicillin-sensitive S. aureus (MSSA) CC80 strains are extremely rare except in sub-Saharan Africa. In the current study, we applied whole-genome sequencing to a global collection of both MSSA and MRSA CC80 isolates. Phylogenetic analyses strongly suggest that the European epidemic CA-MRSA lineage is derived from a PVL-positive MSSA ancestor from sub-Saharan Africa. Moreover, the tree topology suggests a single acquisition of both the SCCmec element and a plasmid encoding the fusidic acid resistance determinant. Four canonical SNPs distinguish the derived CA-MRSA lineage and include a nonsynonymous mutation in accessory gene regulator C (agrC). These changes were associated with a star-like expansion into Europe, the Middle East, and North Africa in the early 1990s, including multiple cases of cross-continent imports likely driven by human migrations. IMPORTANCE: With increasing levels of CA-MRSA reported from most parts of the Western world, there is a great interest in understanding the origin and factors associated with the emergence of these epidemic lineages. To trace the origin, evolution, and dissemination pattern of the European CA-MRSA clone (CC80), we sequenced a global collection of strains of the S. aureus CC80 lineage. Our study determined that a single descendant of a PVL-positive methicillin-sensitive ancestor circulating in sub-Saharan Africa rose to become the dominant CA-MRSA clone in Europe, the Middle East, and North Africa. In the transition from a methicillin-susceptible lineage to a successful CA-MRSA clone, it simultaneously became resistant to fusidic acid, a widely used antibiotic for skin and soft tissue infections, thus demonstrating the importance of antibiotic selection in the success of this clone. This finding furthermore highlights the significance of horizontal gene acquisitions and underscores the combined importance of these factors for the success of CA-MRSA.


Assuntos
Evolução Molecular , Genes Bacterianos , Staphylococcus aureus Resistente à Meticilina/classificação , Staphylococcus aureus Resistente à Meticilina/genética , África do Norte , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Toxinas Bacterianas/genética , Técnicas de Tipagem Bacteriana , Mapeamento Cromossômico , Clonagem Molecular , DNA Bacteriano/genética , Farmacorresistência Bacteriana , Europa (Continente) , Exotoxinas/genética , Leucocidinas/genética , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Oriente Médio , Dados de Sequência Molecular , Análise de Sequência com Séries de Oligonucleotídeos , Filogeografia , Polimorfismo de Nucleotídeo Único , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Análise de Sequência de DNA
18.
Med Princ Pract ; 22 Suppl 1: 20-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24051949

RESUMO

The burden of infections caused by community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is increasing among different patient populations globally. As CA-MRSA has become established in healthcare facilities, the range of infections caused by them has also increased. Molecular characterization of CA-MRSA isolates obtained from different centers has revealed significant diversity in their genetic backgrounds. Although many CA-MRSA strains are still susceptible to non-ß-lactam antibiotics, multiresistance to non-ß-lactam agents has emerged in some clones, posing substantial problems for empirical and directed therapy of infections caused by these strains. Some CA-MRSA clones have acquired the capacity to spread locally and internationally. CA-MRSA belonging to ST80-MRSA-IV and ST30-MRSA-IV appear to be the dominant clones in the countries of the Gulf Cooperation Council (GCC). The emergence of pandemic CA-MRSA clones not only limits therapeutic options but also presents significant challenges for infection control. Continued monitoring of global epidemiology and emerging drug resistance data is critical for the effective management of these infections.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/genética , Técnicas de Tipagem Bacteriana , Infecções Comunitárias Adquiridas , Surtos de Doenças , Farmacorresistência Bacteriana Múltipla/genética , Humanos , Tipagem de Sequências Multilocus
19.
Eur J Med Chem ; 66: 246-57, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23811087

RESUMO

A series of 1H-1,2,3-triazolyl piperazino oxazolidinone analogs with optionally varied glycinyl substitutions were synthesized and their antibacterial activity assessed against a panel of susceptible and resistant Gram-positive and selected Gram-negative bacteria including clinical isolates. The N-aroyl- and N-heteroaroyl-glycinyl (MIC: 0.06-4 µg/ml) derivatives were more potent than the N-acylglycinyl (2-8 µg/ml) derivatives against all Gram-positive bacteria tested. Nitro substitution on aryl and heteroaryl rings significantly enhanced activity against Gram-positive bacteria, as noted with the 3,5-dinitrobenzoyl (6m and 6n) and 5-nitro-2-furoyl (6u and 6v) derivatives with MIC ranges of and 0.25-0.5 and 0.06-0.5 µg/ml, respectively. These nitro analogs also showed more potent extended activity against Moraxella catarrhalis, with MICs ranges of 0.25-1 µg/ml, compared to linezolid (MIC: 8 µg/ml). Hence, the presence of the N-aroyl and/or N-heteroaroyl glycinyl structural motifs as spacer group could significantly enhance the antibacterial activities of 1H-1,2,3-triazolyl oxazolidinone class of compounds.


Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Bactérias Gram-Positivas/efeitos dos fármacos , Oxazolidinonas/síntese química , Oxazolidinonas/farmacologia , Antibacterianos/química , Técnicas de Química Sintética , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Oxazolidinonas/química
20.
Med Princ Pract ; 22: 535-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23635861

RESUMO

OBJECTIVE: To establish the relatedness of methicillin-resistant Staphylococcus aureus (MRSA) isolates in the Maternity Hospital, Kuwait. MATERIALS AND METHODS: A total of 22 MRSA were isolated from 20 neonates and 1 mother in the Special Care Unit, Maternity Hospital, Kuwait. They were characterized using antibiogram, pulsed-field gel electrophoresis (PFGE), SCCmec typing, spa typing and multi locus sequence typing (MLST), and were screened for genes encoding Panton Valentine leukocidin (PVL) and capsular polysaccharide types 5 and 8. RESULTS: The isolates were resistant to cadmium acetate (n = 22 or 100%), trimethoprim (n = 13 or 59.1%), gentamicin (n = 7 or 31.8%), ciprofloxacin (n = 5 or 22.7%), erythromycin and clindamycin (n = 2 or 9.1%), tetracycline (n = 2 or 9.1%) and fusidic acid (n = 2 or 9.1%). Eight isolates contained genes for PVL while 15 and 6 carried genes for types 5 and 8 capsular polysaccharide, respectively. Molecular typing distinguished 12 clones. Ten of these clones consisted of 20 isolates belonging to ST60-SCCmec-IV-t3935 (5 isolates), ST6-SCCmec-IV-t6269 (4 isolates), ST194-SCCmec-IV-t6892 (3 isolates), ST1-SCCmec-V-t2962 (2 isolates) and 1 isolate each of ST77-SCCmec-IV-t339, ST935-SCCmec-V-t1084, ST1317-SCCmec-V-t1548, ST9-SCCmec-V-t5801, ST627-SCCmec-IV-t1340 and ST2148-SCCmec-IV-t2810. CONCLUSION: The study demonstrated the emergence of MRSA including novel ST60 and ST194 clones at the Maternity Hospital in Kuwait.


Assuntos
Infecção Hospitalar/microbiologia , Maternidades , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções Estafilocócicas/microbiologia , Técnicas de Tipagem Bacteriana , Estudos de Coortes , Infecção Hospitalar/classificação , Infecção Hospitalar/diagnóstico , Farmacorresistência Bacteriana , Feminino , Humanos , Recém-Nascido , Kuweit , Staphylococcus aureus Resistente à Meticilina/classificação , Gravidez , Infecções Estafilocócicas/classificação , Infecções Estafilocócicas/diagnóstico
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