Browsing by Author "Whitelaw, Andrew"

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    Antibiotic stewardship ward rounds and a dedicated prescription chart reduce antibiotic consumption and pharmacy costs without affecting inpatient mortality or re-admission rates
    (Public Library of Science, 2013-12-09) Boyles, Tom H.; Whitelaw, Andrew; Bamford, Colleen; Moodley, Mischka; Bonorchis, Kim; Morris, Vida; Rawoot, Naazneen; Naicker, Vanishree; Lusakiewicz, Irena; Black, John; Stead, David; Lesosky, Maia; Raubenheimer, Peter; Dlamini, Sipho; Mendelson, Marc
    Background Antibiotic consumption is a major driver of bacterial resistance. To address the increasing burden of multi-drug resistant bacterial infections, antibiotic stewardship programmes are promoted worldwide to rationalize antibiotic prescribing and conserve remaining antibiotics. Few studies have been reported from developing countries and none from Africa that report on an intervention based approach with outcomes that include morbidity and mortality. Methods An antibiotic prescription chart and weekly antibiotic stewardship ward round was introduced into two medical wards of an academic teaching hospital in South Africa between January-December 2012. Electronic pharmacy records were used to collect the volume and cost of antibiotics used, the patient database was analysed to determine inpatient mortality and 30-day re-admission rates, and laboratory records to determine use of infection-related tests. Outcomes were compared to a control period, January-December 2011. Results During the intervention period, 475.8 defined daily doses were prescribed per 1000 inpatient days compared to 592.0 defined daily doses/1000 inpatient days during the control period. This represents a 19.6% decrease in volume with a cost reduction of 35% of the pharmacy’s antibiotic budget. There was a concomitant increase in laboratory tests driven by requests for procalcitonin. There was no difference in inpatient mortality or 30-day readmission rate during the control and intervention periods. Conclusions Introduction of antibiotic stewardship ward rounds and a dedicated prescription chart in a developing country setting can achieve reduction in antibiotic consumption without harm to patients. Increased laboratory costs should be anticipated when introducing an antibiotic stewardship program.
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    Association between fluoroquinolone resistance and MRSA genotype in Alexandria, Egypt
    (Nature, 2021-02-19) Alseqely, Mustafa; Newton-Foot, Mae; Khalil, Amal; El-Nakeeb, Mostafa; Whitelaw, Andrew; Abouelfetouh, Alaa
    Antimicrobial stewardship isn’t strictly observed in most Egyptian hospitals, raising antibiotic resistance. Epidemiology of Egyptian MRSA isolates, or associations with resistance to other antibiotics remain largely unknown. We identified MRSA genotypes in Alexandria Main University Hospital (AMUH) and investigated rates of moxifloxacin resistance, an alternative MRSA treatment, among different genotypes. Antibiotic susceptibility of 72 MRSA clinical isolates collected in 2015 from AMUH was determined by disc diffusion and broth microdilution. spa- and Staphylococcal Cassette Chromosome mec (SCCmec) typing were performed; with multi-locus sequence typing conducted on isolates representing major genotypes. Resistance to moxifloxacin, levofloxacin and ciprofloxacin were 69%, 78% and 96%, respectively. spa type t037 (57%) was commonest, followed by t127 (12.5%), t267 (8%) and t688 (6%). SCCmec III predominated (57%), all of these were moxifloxacin resistant and 97.6% t037 (ST241). SCCmec IV, IV E and V represented 15%, 7% and 11% of the isolates, respectively, 79% of these were moxifloxacin susceptible and of different spa types. t127 (ST-1) was associated with SCCmec V in 56% of the isolates, mostly moxifloxacin susceptible. Moxifloxacin resistance was high, most resistant isolates belonged to t037 and SCCmec III, suggesting local dissemination and antibiotic pressure. We recommend caution in treating MRSA infections with moxifloxacin.
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    The association between pathogen factors and clinical outcomes in patients with Staphylococcus aureus bacteraemia in a tertiary hospital, Cape Town
    (Elsevier, 2019-11) Abdulgader, Shima M.; van Rijswijk, Amike; Whitelaw, Andrew; Newton-Foot, Mae
    Background: Staphylococcus aureus is a serious pathogen, able to cause life-threatening infections such as bacteraemia. The association between S. aureus microbial characteristics and clinical outcomes is under-investigated in African settings. This study aimed to determine the molecular epidemiology and virulence characteristics of S. aureus isolates from bacteraemic patients at Tygerberg Hospital, South Africa, and to investigate the associations between pathogen characteristics and clinical outcomes. Methods: This study included 199 S. aureus isolates collected from blood cultures between February 2015 and March 2017. Methicillin resistance was determined using disc diffusion and all resistant isolates were further characterized by staphylococcal cassette chromosome mec (SCCmec) typing. Genotyping was done using spa and agr typing, and agr functionality was assessed using the phenotypic δ-haemolysin assay. Logistic regression models were performed to describe the associations between strain characteristics and the clinical outcomes methicillin resistance, in-hospital mortality, and length of stay (LOS). Results: Of the 199 S. aureus isolates collected, 27% were MRSA, and the overall crude in-hospital mortality rate was 29%. Seventy-three different spa types were identified, including seven new types. Agr I was the most common type, in 99 (49.7%) isolates, followed by agr II, III, and IV in 57 (28.6%), 37 (18.6%), and six (3%) isolates, respectively. Agr dysfunctionality was observed in 25 (13%) isolates, mostly belonging to spa-clonal complex (CC) 012. Methicillin resistance was significantly associated with hospital-acquired infection (odds ratio (OR) 4.77, 95% confidence interval (CI) 2.09-10.87). A significant increase in mortality was observed with increasing age (OR 7.48, 95% CI 2.82-19.8) and having a hospital-acquired infection (OR 2.26, 95% CI 1.12-4.55). S. aureus strains with a functional agr system showed an association with longer duration of stay (OR 1.66, 95% CI 0.93-2.99). Conclusions: We report the lowest MRSA prevalence at Tygerberg Hospital for the past 10 years, and agr dysfunctionality was shown to be driven by a certain genotype, spa-CC012. Despite the limited available clinical data, the study provided insights into associations between S. aureus epidemiology and agr-related virulence characteristics, and clinical outcomes.
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    Bacterial disease and antimicrobial susceptibility patterns in HIV-Infected, hospitalized children: A retrospective cohort study
    (PLOS, 2008-09-24) Jaspan, Heather B.; Huang, Lyen C.; Cotton, Mark F.; Whitelaw, Andrew; Myer, Landon
    Background: Serious bacterial infections are a major source of morbidity and mortality in HIV-infected children. The spectrum of disease is wide, and responsible organisms vary according to setting. The use of antibiotic prophylaxis and the emergence of multi-drug resistant bacteria necessitate examination of responsible organisms and their antibiotic susceptibility. Methodology/Principal Findings: A retrospective cohort study of all HIV-positive pediatric admissions at an urban public sector hospital in Cape Town between January 2002 and June 2006 was conducted. Children between the ages of one month and nine years with laboratory confirmed HIV status, serious bacterial infection, and a hospital length of stay of 5 days or more, were eligible for inclusion. Organisms isolated from blood, urine, and cerebral spinal fluid cultures and their antimicrobial susceptibility were examined, and compared according to timing of isolation to distinguish nosocomial versus community-acquired. One hundred and forty-one children were identified (median age 1.2 years), 39% of whom were on antiretrovirals started before or during this hospitalization. Bacterial infections involved all organ systems, however pneumonia was most common (67%). S. pneumoniae and S. aureus were the most common gram positive and K. pneumoniae was the most common gram negative organism. K pneumoniae isolates were resistant to many first and second line antibiotics, and were all considered nosocomial. All S. aureus isolates were methicillin resistant, some of which were community-acquired. Conclusions/Significance: Bacterial infections are an important source of co-morbidity in HIV-infected children in resourcelimited settings. Clinicians should have a low threshold to initiate antibiotics in children requiring hospitalization. Broadspectrum antibiotics should be used judiciously. Clinicians caring for HIV-infected children should be cognizant of the most common organisms affecting such children, and of their local antimicrobial susceptibilities, when treating empirically for serious bacterial infections.
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    Can the Xpert MRSA/SA BC assay be used as an antimicrobial stewardship tool? A prospective assay validation and descriptive impact assessment study in a South African setting
    (BMC (part of Springer Nature), 2021-02-15) Reddy, Kessendri; Whitelaw, Andrew
    Background: Positive blood cultures showing Gram positive cocci in clusters signifies either Staphylococcus aureus or the less-virulent coagulase-negative staphylococci. Rapid identification and methicillin susceptibility determination with the Xpert MRSA/SA BC assay can improve management of S. aureus bloodstream infection and reduce inappropriate antibiotic use. Methods: We prospectively evaluated the Xpert MRSA/SA BC assay in comparison with culture, on samples referred to our laboratory in the Western Cape, South Africa. We interviewed attending clinicians upon culture result availability, to assess antibiotic choices and estimate potential impact of the assay. Results: Of the 231 samples included, there was 100% concordance between the Xpert MRSA/SA BC assay and culture (methicillin-resistant S. aureus 15/15, methicillin-susceptible S. aureus 42/42, coagulase-negative staphylococci 170/170). Time to final result could be reduced by approximately 30 h with the assay. Of the 178 patients with adequate antibiotic history, optimisation of antistaphylococcal therapy could have occurred more than 1 day sooner in 68.9% with S. aureus bloodstream infection (31/45, 95% CI 53.2–81.4%). Six of the 11 patients with methicillin-resistant S. aureus bloodstream infection (54.5%) could have received anti-MRSA cover sooner. Fifty-four days of antibiotic therapy could have been spared, equating to 0.3 days (95% CI, 0.2–0.4) saved per patient, driven by broad-spectrum beta-lactams (32 days, in 18.0% of the cohort). Conclusion: This assay has potential as an antimicrobial stewardship tool; costing and impact on clinical outcome in patients with S. aureus bloodstream infection should be assessed.
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    In vitro activity of tigecycline and comparators against Gram-positive and Gram-negative isolates collected from the Middle East and Africa between 2004 and 2011
    (Elsevier, 2014) Kanj, Souha; Whitelaw, Andrew; Dowzicky, Michael J.
    The Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) was established in 2004 to monitor longitudinal changes in bacterial susceptibility to numerous antimicrobial agents, specifically tigecycline. In this study, susceptibility among Gram-positive and Gram-negative isolates between 2004 and 2011 from the Middle East and Africa was examined. Antimicrobial susceptibilities were determined using Clinical and Laboratory Standards Institute (CLSI) interpretive criteria, and minimum inhibitory concentrations (MICs) were determined by broth microdilution methods. US Food and Drug Administration (FDA)-approved breakpoints were used for tigecycline. In total, 2967 Gram-positive and 6322 Gram-negative isolates were examined from 33 participating centres. All Staphylococcus aureus isolates, including meticillin-resistant S. aureus, were susceptible to tigecycline, linezolid and vancomycin. Vancomycin, linezolid, tigecycline and levofloxacin were highly active (>97.6% susceptibility) against Streptococcus pneumoniae, including penicillin-non-susceptible strains. All Enterococcus faecium isolates were susceptible to tigecycline and linezolid, including 32 vancomycin-resistant isolates. Extended-spectrum β-lactamases were produced by 16.6% of Escherichia coli and 32.9% of Klebsiella pneumoniae. More than 95% of E. coli and Enterobacter spp. were susceptible to amikacin, tigecycline, imipenem and meropenem. The most active agents against Pseudomonas aeruginosa and Acinetobacter baumannii were amikacin (88.0% susceptible) and minocycline (64.2% susceptible), respectively; the MIC90 (MIC required to inhibit 90% of the isolates) of tigecycline against A. baumannii was low at 2 mg/L. Tigecycline and carbapenem agents were highly active against most Gram-negative pathogens. Tigecycline, linezolid and vancomycin showed good activity against most Gram-positive pathogens from the Middle East and Africa.
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    Laboratory based antimicrobial resistance surveillance for Pseudomonas aeruginosa blood isolates from South Africa
    (Journal of Infection in Developing Countries, 2018) Singh-Moodley, Ashika; Duse, Adriano; Naicker, Preneshni; Kularatne, Ranmini; Nana, Trusha; Lekalakala, Ruth; Mbelle, Nontombi; Dawood, Halima; Han, Khine Swe Swe; Ramjathan, Praksha; Bhola, Prathna; Whitelaw, Andrew; Perovic, Olga
    Introduction: Antimicrobial resistant bacterial infections are widespread globally and increases in antimicrobial resistance presents a major threat to public health. Pseudomonas aeruginosa is an opportunistic healthcare-associated pathogen with high rates of morbidity and mortality and an extensive range of resistance mechanisms. This study describes the antibiotic susceptibility profiles of P. aeruginosa isolates from patients with bacteraemia submitted by sentinel laboratories in South Africa from 2014 to 2015. Methodology: Organism identification and antimicrobial susceptibility testing were done using automated systems. Molecular methods were used to detect common resistance genes and mechanisms. Results: Overall the susceptibility was high for all antibiotics tested with a decrease over the two-year period. There was no change in the MIC50 and MIC90 breakpoints for all antibiotics from 2014 to 2015. The MIC50 was within the susceptible breakpoint range for most antibiotics and the MIC90 was within the susceptible breakpoint range for colistin only. Phenotypically carbapenem non-susceptible isolates harboured the following plasmid-mediated genes: blaVIM (n = 81, 12%) and blaGES (n = 6, 0.9%); blaNDM (n = 4, 0.6%) and blaOXA-48 and variants (n = 3, 0.45%). Porin deletions were observed in one meropenem non-susceptible isolate only, and multi-drug resistance efflux pumps were expressed in the majority of the non-susceptible isolates investigated. BlaVEB-1, blaIMP and blaKPC were not detected. Conclusion: The prevalence of resistance to commonly used antibacterial agents was low for P. aeruginosa isolates and similarly, tested resistance mechanisms were detected in a relatively small proportion of isolates. Findings in this study represent baseline information for understanding antimicrobial susceptibility patterns in P. aeruginosa isolates from blood. Our surveillance report may assist in contributing to hospital treatment guidelines.
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    Molecular characterization of Staphylococcus aureus isolates from various healthcare institutions in Nairobi, Kenya : a cross sectional study
    (BioMed Central, 2016-09-20) Omuse, Geoffrey; Van Zyl, Kristien Nel.; Hoek, Kim; Abdulgader, Shima; Kariuki, Samuel; Whitelaw, Andrew; Revathi, Gunturu
    Background: Staphylococcus aureus (S. aureus) has established itself over the years as a major cause of morbidity and mortality both within the community and in healthcare settings. Methicillin resistant S. aureus (MRSA) in particular has been a major cause of nosocomial infections resulting in significant increase in healthcare costs. In Africa, the MRSA prevalence has been shown to vary across different countries. In order to better understand the epidemiology of MRSA in a setting, it is important to define its population structure using molecular tools as different clones have been found to predominate in certain geographical locations. Methods: We carried out PFGE, MLST, SCCmec and spa typing of selected S. aureus isolates from a private and public referral hospital in Nairobi, Kenya. Results: A total of 93 S. aureus isolates were grouped into 19 PFGE clonal complexes (A–S) and 12 singletons. From these, 55 (32 MRSA and 23 MSSA) representative isolates from each PFGE clonal complex and all singletons were spa typed. There were 18 different MRSA spa types and 22 MSSA spa types. The predominant MRSA spa type was t037 comprising 40.6 % (13/32) of all MRSA. In contrast, the MSSA were quite heterogeneous, only 2 out of 23 MSSA shared the same spa type. Two new MRSA spa types (t13149 and t13150) and 3 new MSSA spa types (t13182, t13193 and t13194) were identified. The predominant clonal complex was CC 5 which included multi-locus sequence types 1, 8 and 241. Conclusion: In contrast to previous studies published from Kenya, there’s marked genetic diversity amongst clinical MRSA isolates in Nairobi including the presence of well-known epidemic MRSA clones. Given that these clones are resident within our referral hospitals, adherence to strict infection control measures needs to be ensured to reduce morbidity and mortality associated with hospital acquired MRSA infections.
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    National sentinel site surveillance for antimicrobial resistance in Klebsiella pneumoniae isolates in South Africa, 2010-2012
    (Health & Medical Publishing Group, 2014-08) Perovic, Olga; Singh-Moodley, Ashika; Duse, Adriano; Bamford, Colleen; Elliott, G.; Swe-Han, Khine Swe; Kularatne, Ranmini; Lowman, Warren; Whitelaw, Andrew; Nana, Trusha; Wadula, Jeanette; Lekalakala, Ruth; Saif, Adrienne; Fortuin De-Smit, Melony; Marais, Else
    Background. The increasing rates of antimicrobial resistance observed in the nosocomial pathogen Klebsiella pneumoniae are of major public health concern worldwide. Objectives. To describe the antibiotic susceptibility profiles of K. pneumoniae isolates from bacteraemic patients submitted by sentinel laboratories in five regions of South Africa from mid-2010 to mid-2012. Molecular methods were used to detect the most commonly found extended-spectrum beta-lactamase (ESBL) and carbapenemase resistance genes. Methods. Thirteen academic centres serving the public healthcare sector in Gauteng, KwaZulu-Natal, Free State, Limpopo and Western Cape provinces submitted K. pneumoniae isolates from patients with bloodstream infections. Vitek 2 and MicroScan instruments were used for organism identification and susceptibility testing. Multiplex polymerase chain reactions (PCRs) were used to detect blaCTX-M, blaSHV and blaTEM genes in a proportion of the ESBL isolates. All isolates exhibiting reduced susceptibility to carbapenems were PCR tested for blaKPC and blaNDM-1 resistance genes. Results. Overall, 68.3% of the 2 774 isolates were ESBL-positive, showing resistance to cefotaxime, ceftazidime and cefepime. Furthermore, 46.5% of all isolates were resistant to ciprofloxacin and 33.1% to piperacillin-tazobactam. The major ESBL genes were abundantly present in the sample analysed. Most isolates (95.5%) were susceptible to the carbapenems tested, and no isolates were positive for blaKPC or blaNDM-1. There was a trend towards a decrease in susceptibility to most antibiotics. Conclusion. The high proportion of ESBL-producing K. pneumoniae isolates observed, and the prevalence of ESBL genes, are of great concern. Our findings represent a baseline for further surveillance in SA, and can be used for policy and treatment decisions.
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    Pneumocystis pneumonia in South African children diagnosed by molecular methods
    (BioMed Central, 2014-01) Morrow, Brenda M.; Samuel, Catherine M.; Zampoli, Marco; Whitelaw, Andrew; Zar, Heather J.
    Abstract Background Pneumocystis pneumonia (PCP) is an important cause of hospitalization and mortality in HIV-infected children. However, the incidence of PCP has been underestimated due to poor sensitivity of diagnostic tests. The use of polymerase chain reaction (PCR) for pneumocystis has enabled more reliable diagnosis. This study describes the incidence, clinical features and outcome of PCP in South African children diagnosed using PCR. Methods A prospective study of children hospitalised in South Africa with suspected PCP was done from November 2006 to August 2008. Clinical, laboratory and radiological information were collected. Lower respiratory tract specimens were obtained for PCP immunofluorescence (IF), real- time PCR for pneumocystis, bacterial and mycobacterial culture. Nasopharyngeal aspirates were taken for immunofluorescence (IF), real-time PCR for pneumocystis and PCR for respiratory viruses. A blood specimen for bacterial culture and for cytomegalovirus PCR was taken. Children were followed for the duration of their hospitalisation and the outcome was recorded. Results 202 children [median (interquartile range, IQR) age 3.2 (2.1– 4.6) months] were enrolled; 124 (61.4%) were HIV infected. PCP was identified in 109 (54%) children using PCR, compared to 43 (21%) using IF and Grocott staining (p < 0.0001). Most PCP cases (88, 81%) occurred in HIV-infected children. All 21 cases (19%) occurring in HIV- negative children had another risk factor for PCP. On logistic regression, predictive factors for PCP were HIV infection, lack of fever, high respiratory rate and low oxygen saturation whilst cotrimoxazole prophylaxis was protective (OR 0.24; 95% CI 0.1 to 0.5; p < 0.002). The case fatality of children with PCP was higher than those without PCP (32.1% versus 17.2%; relative risk 1.87; 95% confidence interval (CI) 1.11 – 3.15). Amongst HIV-infected children, a CD4 less than 15% was the only independent predictor of mortality. Conclusions The diagnostic yield for PCP is more than 2.5 times higher on PCR than other detection methods. PCP is a very common cause of severe hypoxic pneumonia and is associated with high mortality in HIV-infected African infants.
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    Predominance of Central Asian strain (ST 26) in Mycobacterium tuberculosis isolates from Balochistan by spoligotyping
    (JIDC, 2019-07) Shafee, Muhammad; Abbas, Ferhat; Tanveer, Zunera; Whitelaw, Andrew; Tow, Lemese Ah; Ashraf, Muhammad; Ahmad, Irshad; Patching, Simon G.; Jabbar, Abdul; Akbar, Ali; Mustafa, Mohammad Zahid
    Introduction: Tuberculosis is a chronic debilitating infectious disease causing a severe challenge to public health, especially in developing countries. The aim of this study was to examine genetic diversity in Mycobacterium tuberculosis strains circulating in the Balochistan region of Pakistan. Methodology: One hundred isolates collected from patients visiting the Fatima Jinnah TB Hospital in Quetta were subjected to genotype analysis by spoligotyping. Results: Three main genotypes were identified: Central Asian Strain 1 (CAS1) (n = 89), East African Indian (EAI) strain (n = 7) and Latin American Mediterranean (LAM) strain (n = 3). The CAS1 clade (ST 26) had high genetic diversity represented by seven different spoligopatterns, of which one had major predominace (n = 75). Conclusions: This is the first insight into the genotype of M. tuberculosis strains in the Balochistan region that might serve as a base line study for control of tuberculosis in the community.
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    The prevalence and molecular mechanisms of mupirocin resistance in Staphylococcus aureus isolates from a Hospital in Cape Town, South Africa
    (BMC (part of Springer Nature), 2020-03-14) Abdulgader, Shima M.; Lentswe, Tshepiso; Whitelaw, Andrew; Newton-Foot, Mae
    Abstract Background: Antimicrobial resistance is an increasingly serious problem in public health globally. Monitoring resistance levels within healthcare and community settings is critical to combat its ongoing increase. This study aimed to describe the rates and molecular mechanisms of mupirocin resistance in clinical Staphylococcus aureus isolates from Tygerberg Hospital, and to describe its association with strain types. Methods: We retrospectively selected 212 S. aureus isolates which were identified from blood samples and pus swabs during the years 2009–2011 and 2015–2017. The isolates were identified using conventional microbiological methods and genotyping was done using spa typing. Cefoxitin (30 μg) disc diffusion and the two disc strategy (5 μg and 200 μg) were used to determine susceptibility to methicillin and mupirocin, respectively. Isolates with high-level resistance were screened for the plasmid mediated genes mupA and mupB by PCR, and sequencing of the ileS gene was done for all isolates exhibiting low-level resistance to describe the mutations associated with this phenotype. Chi-square test was used to assess the associations between mupirocin resistance and S. aureus genotypes. Results: Of 212 S. aureus isolates, 12% (n = 25) were resistant to mupirocin, and 44% (n = 93) were methicillin resistant. Strain typing identified 73 spa types with spa t045 being the most predominant constituting 11% of the isolates. High-level mupirocin resistance was observed in 2% (n = 5), and low-level resistance in 9% (n = 20) of the isolates. The prevalence of high-level mupirocin resistance amongst MRSA and MSSA was 4 and 1% respectively, while the prevalence of low-level mupirocin resistance was significantly higher in MRSA (18%) compared to MSSA (3%), (p = 0.032). mupA was the only resistance determinant for high-level resistance, and the IleS mutation V588F was identified in 95% of the isolates which showed low-level resistance. A significant association was observed between spa type t032 and high-level mupirocin resistance, and types t037 and t012 and low-level resistance (p < 0.0001). Conclusion: The study reported higher rates of low-level mupirocin resistance compared to high-level resistance, and in our setting, mupirocin resistance was driven by certain genotypes. Our study advocates for the continuous screening for mupirocin resistance in S. aureus in clinical settings to better guide treatment and prescribing practices. Background Antimicrobial resistance is an increasingly serious problem in public health globally. Monitoring resistance levels within healthcare and community settings is critical to combat its ongoing increase. This study aimed to describe the rates and molecular mechanisms of mupirocin resistance in clinical Staphylococcus aureus isolates from Tygerberg Hospital, and to describe its association with strain types. Methods We retrospectively selected 212 S. aureus isolates which were identified from blood samples and pus swabs during the years 2009–2011 and 2015–2017. The isolates were identified using conventional microbiological methods and genotyping was done using spa typing. Cefoxitin (30 μg) disc diffusion and the two disc strategy (5 μg and 200 μg) were used to determine susceptibility to methicillin and mupirocin, respectively. Isolates with high-level resistance were screened for the plasmid mediated genes mupA and mupB by PCR, and sequencing of the ileS gene was done for all isolates exhibiting low-level resistance to describe the mutations associated with this phenotype. Chi-square test was used to assess the associations between mupirocin resistance and S. aureus genotypes. Results Of 212 S. aureus isolates, 12% (n = 25) were resistant to mupirocin, and 44% (n = 93) were methicillin resistant. Strain typing identified 73 spa types with spa t045 being the most predominant constituting 11% of the isolates. High-level mupirocin resistance was observed in 2% (n = 5), and low-level resistance in 9% (n = 20) of the isolates. The prevalence of high-level mupirocin resistance amongst MRSA and MSSA was 4 and 1% respectively, while the prevalence of low-level mupirocin resistance was significantly higher in MRSA (18%) compared to MSSA (3%), (p = 0.032). mupA was the only resistance determinant for high-level resistance, and the IleS mutation V588F was identified in 95% of the isolates which showed low-level resistance. A significant association was observed between spa type t032 and high-level mupirocin resistance, and types t037 and t012 and low-level resistance (p <  0.0001). Conclusion The study reported higher rates of low-level mupirocin resistance compared to high-level resistance, and in our setting, mupirocin resistance was driven by certain genotypes. Our study advocates for the continuous screening for mupirocin resistance in S. aureus in clinical settings to better guide treatment and prescribing practices.
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    Rationale and design of the African group A streptococcal infection registry : the AFROStrep study
    (BMJ Publishing Group, 2016) Barth, Dylan D.; Engel, Mark E.; Whitelaw, Andrew; Alemseged, Abdissa; Sadoh, Wilson E.; Ali, Sulafa K. M.; Sow, Samba O.; Dale, James; Mayosi, Bongani M
    Introduction: Group A β-haemolytic Streptococcus (GAS), a Gram-positive bacterium, also known as Streptococcus pyogenes, causes pyoderma, pharyngitis and invasive disease. Repeated GAS infections may lead to autoimmune diseases such as acute post-streptococcal glomerulonephritis, acute rheumatic fever (ARF) and rheumatic heart disease (RHD). Invasive GAS (iGAS) disease is an important cause of mortality and morbidity worldwide. The burden of GAS infections is, however, unknown in Africa because of lack of surveillance systems. Methods and analysis: The African group A streptococcal infection registry (the AFROStrep study) is a collaborative multicentre study of clinical, microbiological, epidemiological and molecular characteristics for GAS infection in Africa. The AFROStrep registry comprises two components: (1) active surveillance of GAS pharyngitis cases from sentinel primary care centres (non-iGAS) and (2) passive surveillance of iGAS disease from microbiology laboratories. Isolates will also be subjected to DNA isolation to allow for characterisation by molecular methods and cryopreservation for long-term storage. The AFROStrep study seeks to collect comprehensive data on GAS isolates in Africa. The biorepository will serve as a platform for vaccine development in Africa. Ethics and dissemination: Ethics approval for the AFROStrep registry has been obtained from the Human Research Ethics Committee at the University of Cape Town (HREC/REF: R006/2015). Each recruiting site will seek ethics approval from their local ethics’ committee. All participants will be required to provide consent for inclusion into the registry as well as for the storage of isolates and molecular investigations to be conducted thereon. Strict confidentiality will be applied throughout. Findings and updates will be disseminated to collaborators, researchers, health planners and colleagues through peer-reviewed journal articles, conference publications and proceedings.
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    Screening for HIV-associated tuberculosis and rifampicin resistance before antiretroviral therapy using the Xpert MTB/RIF assay : a prospective study
    (Public Library of Science, 2011-07-26) Lawn, Stephen D.; Brooks, Sophie V.; Kranzer, Katharina; Nicol, Mark P.; Whitelaw, Andrew; Vogt, Monica; Bekker, Linda-Gail; Wood, Robin
    Background: The World Health Organization has endorsed the Xpert MTB/RIF assay for investigation of patients suspected of having tuberculosis (TB). However, its utility for routine TB screening and detection of rifampicin resistance among HIV-infected patients with advanced immunodeficiency enrolling in antiretroviral therapy (ART) services is unknown. Methods and Findings: Consecutive adult HIV-infected patients with no current TB diagnosis enrolling in an ART clinic in a South African township were recruited regardless of symptoms. They were clinically characterised and invited to provide two sputum samples at a single visit. The accuracy of the Xpert MTB/RIF assay for diagnosing TB and drug resistance was assessed in comparison with other tests, including fluorescence smear microscopy and automated liquid culture (gold standard) and drug susceptibility testing. Of 515 patients enrolled, 468 patients (median CD4 cell count, 171 cells/μl; interquartile range, 102-236) produced at least one sputum sample, yielding complete sets of results from 839 samples. Mycobacterium tuberculosis was cultured from 81 patients (TB prevalence, 17.3%). The overall sensitivity of the Xpert MTB/RIF assay for culture-positive TB was 73.3% (specificity, 99.2%) compared to 28.0% (specificity, 100%) using smear microscopy. All smear-positive, culture-positive disease was detected by Xpert MTB/RIF from a single sample (sensitivity, 100%), whereas the sensitivity for smear-negative, culture-positive TB was 43.4% from one sputum sample and 62.3% from two samples. Xpert correctly identified rifampicin resistance in all four cases of multidrug-resistant TB but incorrectly identified resistance in three other patients whose disease was confirmed to be drug sensitive by gene sequencing (specificity, 94.1%; positive predictive value, 57%). Conclusions: In this population of individuals at high risk of TB, intensive screening using the Xpert MTB/RIF assay increased case detection by 45% compared with smear microscopy, strongly supporting replacement of microscopy for this indication. However, despite the ability of the assay to rapidly detect rifampicin-resistant disease, the specificity for drug-resistant TB was sub-optimal. © 2011 Lawn et al.
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    Stool culture for diagnosis of pulmonary tuberculosis in children
    (American Society for Microbiology, 2017-12) Walters, Elisabetta; Demers, Anne-Marie; Van der Zalm, Marieke M.; Whitelaw, Andrew; Palmer, Megan; Bosch, Corne; Draper, Heather R.; Gie, Robert P.; Hesseling, Anneke C.
    Bacteriological confirmation of Mycobacterium tuberculosis is achieved in the minority of young children with tuberculosis (TB), since specimen collection is resource intensive and respiratory secretions are mostly paucibacillary, leading to limited sensitivity of available diagnostic tests. Although molecular tests are increasingly available globally, mycobacterial culture remains the gold standard for diagnosis and determination of drug susceptibility and is more sensitive than molecular methods for paucibacillary TB. We evaluated stool culture as an alternative to respiratory specimens for the diagnosis of suspected intrathoracic TB in a subgroup of 188 children (median age, 14.4 months; 15.4% HIV infected) enrolled in a TB diagnostic study at two local hospitals in Cape Town, South Africa. One stool culture was compared to overall bacteriological confirmation by stool Xpert and by Xpert and culture of multiple respiratory specimens. After decontamination/digestion with NALC (N-acetyl-l-cysteine)-NaOH (1.25%), concentrated fluorescent smear microscopy, Xpert MTB/RIF, and liquid culture were completed for all specimens. Culture contamination of stool specimens was high at 41.5%. Seven of 90 (7.8%) children initiating TB treatment were stool culture positive for M. tuberculosis. Excluding contaminated cultures, the sensitivity of stool culture versus confirmed TB was 6/25 (24.0%; 95% confidence interval [CI] = 9.4 to 45.1%). In addition, stool culture detected TB in 1/93 (1.1%) children with “unconfirmed TB.” Testing the same stool by Xpert increased sensitivity to 33.3% (95% CI = 18.0 to 51.8%). In conclusion, stool culture had low sensitivity for M. tuberculosis detection in children with intrathoracic TB. Reducing culture contamination through improved laboratory protocols may enable more reliable estimates of its diagnostic utility.
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    Trends in paediatric bloodstream infections at a South African referral hospital
    (BioMed Central, 2015-04) Dramowski, Angela; Cotton, Mark F.; Rabie, Helena; Whitelaw, Andrew
    Background: The epidemiology of paediatric bloodstream infection (BSI) in Sub-Saharan Africa is poorly documented with limited data on hospital-acquired sepsis, impact of HIV infection, BSI trends and antimicrobial resistance. Methods: We retrospectively reviewed paediatric BSI (0–14 years) at Tygerberg Children’s Hospital between 1 January 2008 and 31 December 2013 (excluding neonatal wards). Laboratory and hospital data were used to determine BSI rates, blood culture contamination, pathogen profile, patient demographics, antimicrobial resistance and factors associated with mortality. Fluconazole resistant Candida species, methicillin-resistant Staphylococcus aureus (MRSA), multi-drug resistant Acinetobacter baumannii and extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae were classified as antimicrobial resistant pathogens. Results: Of 17001 blood cultures over 6 years, 935 cultures isolated 979 pathogens (5.5% yield; 95% CI 5.3-5.7%). Contamination rates were high (6.6%, 95% CI 6.4-6.8%), increasing over time (p = 0.003). Discrete BSI episodes were identified (n = 864) with median patient age of 7.5 months, male predominance (57%) and 13% HIV prevalence. BSI rates declined significantly over time (4.6–3.1, overall rate 3.5 per 1000 patient days; 95% CI 3.3–3.7; Chi square for trend p = 0.02). Gram negative pathogens predominated (60% vs 33% Gram positives and 7% fungal); Klebsiella pneumoniae (154; 17%), Staphylococcus aureus (131; 14%) and Escherichia coli (97; 11%) were most prevalent. Crude BSI mortality was 20% (176/864); HIV infection, fungal, Gram negative and hospital-acquired sepsis were significantly associated with mortality on multivariate analysis. Hospital-acquired BSI was common (404/864; 47%). Overall antimicrobial resistance rates were high (70% in hospital vs 25% in community-acquired infections; p < 0.0001); hospital-acquired infection, infancy, HIV-infection and Gram negative sepsis were associated with resistance. S. pneumoniae BSI declined significantly over time (58/465 [12.5%] to 33/399 [8.3%]; p =0.04). Conclusion: Although BSI rates declined over time, children with BSI had high mortality and pathogens exhibited substantial antimicrobial resistance in both community and hospital-acquired infections. Blood culture sampling technique and local options for empiric antimicrobial therapy require re-evaluation.
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    Utilization of paediatric isolation facilities in a TB-endemic setting
    (BioMed Central, 2015-09) Dramowski, Angela; Cotton, Mark F.; Whitelaw, Andrew
    Introduction: In hospital settings, patient isolation is used to limit transmission of certain pathogens (e.g. M. tuberculosis [TB], antibiotic-resistant bacteria and viruses causing respiratory and enteric infection). Data is lacking on utilization of paediatric isolation facilities in low-resource, TB-endemic settings. Methods: Prospective weekday observation of 18 paediatric isolation rooms at Tygerberg Children’s Hospital, Cape Town, South Africa, was conducted between 1 May 2014 and 31 October 2014 documenting: occupancy rate; indication for isolation; duration of isolation; application of transmission-based precautions and infection prevention (IPC) behaviour of personnel. Potential under-utilization of isolation rooms was determined by cross-referencing isolation room occupancy with laboratory isolates of antibiotic-resistant bacteria, M. tuberculosis and selected viral pathogens. Results: Six percent (335/5906) of hospitalized children were isolated: 78 % (260/335) for IPC purposes. Most IPC-isolated patients had community-acquired infections (213/260; 82 %), including tuberculosis (130/260; 50 %) and suspected viral infections (75/260; 29 %). Children (median age 17 months [IQR 6–50]) spent 4 days (IQR 2–8) in isolation. Isolation occupancy was 66 % (2172/3294 occupied bed days), but varied significantly by month. Laboratory data identified an additional 135 patients warranting isolation with 2054 extra bed-days required. Forty patients with 171 patient days of inappropriate isolation were identified. During 1223 weekday visits to IPC-isolated patient rooms: alcohol-based handrub was available (89 %); transmission-based precautions were appropriately implemented (71 %); and personal protective equipment was provided (74 %). Of 358 observed interactions between paediatric staff and isolated patients, hand hygiene compliance was 65 % and adherence to transmission-based precautions was 58 %. Conclusion: Patients isolated for TB (under airborne precautions) accounted for more than half of all isolation episodes. Missed opportunities for patient isolation were common but could be reduced by implementation of syndromic isolation. Demand for isolation facilities was seasonal, with projected demand exceeding available isolation beds over winter months.