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      Antibiotic resistance and molecular epidemiology of Staphylococcus aureus in Nigeria

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          Abstract

          Background

          Staphylococcus aureus is an important pathogen causing a wide range of infections in the hospital and community setting. In order to have adequate information for treatment of S. aureus infections, it is crucial to understand the trends in the antibiotic-resistance patterns. In addition, the occurrence and changes in types of S. aureus, clonal identities, and their geographic spread is essential for the establishment of adequate infection control programmes. In this study, 68 S. aureus isolates obtained from clinical and non-clinical sources in Nigeria between January and April 2009 were characterized using phenotypic and molecular methods.

          Results

          All the S. aureus isolates were susceptible to teicoplanin, vancomycin, phosphomycin, fusidic acid, rifampicin, daptomycin, mupirocin, linezolid and tigecycline. Sixteen percent of the isolates were resistant to oxacillin, while 55% and 72% of isolates were resistant to tetracycline and trimethoprim/sulphamethoxazole (cotrimoxazole), respectively (Table 1). There was excellent correlation between the broth microdilution assay and detection of antibiotic resistance genes by the multiplex PCR, in the determination of S. aureus resistance to erythromycin, gentamicin, methicillin and tetracycline. A total of 28 spa types were identified in the study, and the predominant spa type among the methicillin-susceptible S. aureus (MSSA) isolates was t084 (13 isolates). The t037-ST241-SCC mecIII type was the only clone identified in Maiduguri (North-East Nigeria) while in South-West Nigeria, diversity among the MRSA isolates (t451-ST8-SCC mecV; t008-ST94-SCC mecIV; t002-ST5-SCC mecV; t064-ST8-SCC mecV) was observed. The toxin genes seh and etd were detected in isolates affiliated with clonal complexes CC1, CC80 and sequence type ST25, respectively. The proportion of PVL-positive isolates among MSSA was high (40%). Most of the PVL-positive MSSA isolates were obtained from wound infections and associated with clonal complexes CC1, CC30, CC121 and with sequence type ST152.

          Table 1

          Antibiotic resistance profile of S. aureu s (MSSA and MRSA) from Nigeria

          Number (%) of resistant isolates among:
          Antibiotic MSSA

          (n = 57)
          MRSA

          (n = 11)
          Total

          (n = 68)
          Penicillin 49 (86) 11 (100) 60 (88.2)
          Oxacillin 0 (0) 11 (100) 11 (16.2)
          Teicoplanin 0 (0) 0 (0) 0 (0)
          Vancomycin 0 (0) 0 (0) 0 (0)
          Gentamicin 1 (1.8) 9 (81.8) 10 (14.7)
          Tetracycline 27 (47.4) 11 (100) 38 (55.9)
          Ciprofloxacin 12 (21.1) 8 (72.7) 20 (29.4)
          Moxifloxacin 0 (0) 7 (63.6) 7 (10.3)
          Trimethoprim/sulfamethoxazole 39 (68.4) 10 (90.9) 49 (72.1)
          Phosphomycin 0 (0) 0 (0) 0 (0)
          Fusidic acid 0 (0) 0 (0) 0 (0)
          Erythromycin 2 (3.5) 6 (54.5) 8 (11.8)
          Clindamycin 0 (0) 6 (54.5) 6 (8.8)
          Rifampicin 0 (0) 0 (0) 0 (0)
          Daptomycin 0 (0) 0 (0) 0 (0)
          Mupirocin 0 (0) 0 (0) 0 (0)
          Linezolid 0 (0) 0 (0) 0 (0)
          Tigecycline 0 (0) 0 (0) 0 (0)
          Conclusions

          The use of phenotypic and molecular methods provided useful information on antibiotic resistance and molecular diversity of S. aureus in Nigeria. The high proportion of PVL-positive MSSA isolates affiliated to various clonal complexes and detected in all the health institutions is a major concern, both as a source of severe infections and as a potential reservoir that could lead to the emergence of PVL-positive MRSA. This study presents the first baseline information on the nature of the antibiotic resistance genes from S. aureus isolates in Nigeria. There is the need to curtail the spread and establishment of MRSA and PVL-positive MSSA clones in Nigerian health care institutions.

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          Most cited references44

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          Nosocomial infections in medical intensive care units in the United States. National Nosocomial Infections Surveillance System.

          To describe the epidemiology of nosocomial infections in medical intensive care units (ICUs) in the United States. Analysis of ICU surveillance data collected through the National Nosocomial Infections Surveillance (NNIS) System between 1992 and 1997. Medical ICUs in the United States. A total of 181,993 patients. Nosocomial infections were analyzed by infection site and pathogen distribution. Urinary tract infections were most frequent (31%), followed by pneumonia (27%) and primary bloodstream infections (19%). Eighty-seven percent of primary bloodstream infections were associated with central lines, 86% of nosocomial pneumonia was associated with mechanical ventilation, and 95% of urinary tract infections were associated with urinary catheters. Coagulase-negative staphylococci (36%) were the most common bloodstream infection isolates, followed by enterococci (16%) and Staphylococcus aureus (13%). Twelve percent of bloodstream isolates were fungi. The most frequent isolates from pneumonia were Gram-negative aerobic organisms (64%). Pseudomonas aeruginosa (21%) was the most frequently isolated of these. S. aureus (20%) was isolated with similar frequency. Candida albicans was the most common single pathogen isolated from urine and made up just over half of the fungal isolates. Fungal urinary infections were associated with asymptomatic funguria rather than symptomatic urinary tract infections (p < .0001). Certain pathogens were associated with device use: coagulase-negative staphylococci with central lines, P. aeruginosa and Acinetobacter species with ventilators, and fungal infections with urinary catheters. Patient nosocomial infection rates for the major sites correlated strongly with device use. Device exposure was controlled for by calculating device-associated infection rates for bloodstream infections, pneumonia, and urinary tract infections by dividing the number of device-associated infections by the number of days of device use. There was no association between these device-associated infection rates and number of hospital beds, number of ICU beds, or length of stay. There is a considerable variation within the distribution of each of these infection rates. The distribution of sites of infection in medical ICUs differed from that previously reported in NNIS ICU surveillance studies, largely as a result of anticipated low rates of surgical site infections. Primary bloodstream infections, pneumonia, and urinary tract infections associated with invasive devices made up the great majority of nosocomial infections. Coagulase-negative staphylococci were more frequently associated with primary bloodstream infections than reported from NNIS ICUs of all types in the 1980s, and enterococci were a more frequent isolate from bloodstream infections than S. aureus. Fungal urinary tract infections, often asymptomatic and associated with catheter use, were considerably more frequent than previously reported. Invasive device-associated infections were associated with specific pathogens. Although device-associated site-specific infection rates are currently our most useful rates for performing comparisons between ICUs, the considerable variation in these rates between ICUs indicates the need for further risk adjustment.
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            The emergence and evolution of methicillin-resistant Staphylococcus aureus.

            Significant advances have been made in recent years in our understanding of how methicillin resistance is acquired by Staphylococcus aureus. Integration of a staphylococcal cassette chromosome mec (SCCmec) element into the chromosome converts drug-sensitive S. aureus into the notorious hospital pathogen methicilin-resistant S. aureus (MRSA), which is resistant to practically all beta-lactam antibiotics. SCCmec is a novel class of mobile genetic element that is composed of the mec gene complex encoding methicillin resistance and the ccr gene complex that encodes recombinases responsible for its mobility. These elements also carry various resistance genes for non-beta-lactam antibiotics. After acquiring an SCCmec element, MRSA undergoes several mutational events and evolves into the most difficult-to-treat pathogen in hospitals, against which all extant antibiotics including vancomycin are ineffective. Recent epidemiological data imply that MRSA has embarked on another evolutionary path as a community pathogen, as at least one novel SCCmec element seems to have been successful in converting S. aureus strains from the normal human flora into MRSA.
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              Multiplex PCR assay for simultaneous detection of nine clinically relevant antibiotic resistance genes in Staphylococcus aureus.

              In this study we describe a multiplex PCR assay for the detection of nine clinically relevant antibiotic resistance genes of Staphylococcus aureus. Conditions were optimized to amplify fragments of mecA (encoding methicillin resistance), aacA-aphD (aminoglycoside resistance), tetK, tetM (tetracycline resistance), erm(A), erm(C) (macrolide-lincosamide-streptogramin B resistance), vat(A), vat(B), and vat(C) (streptogramin A resistance) simultaneously in one PCR amplification. An additional primer pair for the amplification of a fragment of the staphylococcal 16S rDNA was included as a positive control. The multiplex PCR assay was evaluated on 30 different S. aureus isolates, and the PCR results correlated with the phenotypic antibiotic resistance data obtained by the broth microdilution assay. The multiplex PCR assay offers a rapid, simple, and accurate identification of antibiotic resistance profiles and could be used in clinical diagnosis as well as for the surveillance of the spread of antibiotic resistance determinants in epidemiological studies.
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                Author and article information

                Journal
                BMC Microbiol
                BMC Microbiology
                BioMed Central
                1471-2180
                2011
                5 May 2011
                : 11
                : 92
                Affiliations
                [1 ]Department of Microbiology, Obafemi Awolowo University, Ile-Ife, Nigeria
                [2 ]Department of Medical Microbiology, University of Maiduguri Teaching Hospital, Maiduguri, Nigeria
                [3 ]Molecular Biology and Biotechnology Division, Nigerian Institute of Medical Research, Lagos, Nigeria
                [4 ]Department of Biological Sciences, College of Science, Engineering and Technology, Osun State University, Osogbo, Nigeria
                [5 ]Robert Koch Institute, 38855 Wernigerode, Germany
                Article
                1471-2180-11-92
                10.1186/1471-2180-11-92
                3112067
                21545717
                61594703-e46b-4bf2-a010-7b9ff0dd7998
                Copyright ©2011 Shittu et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 22 December 2010
                : 5 May 2011
                Categories
                Research Article

                Microbiology & Virology
                Microbiology & Virology

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