Olga Perovic

Gender as a Risk Factor for Both Antibiotic Resistance and Infection with Pediatric Serogroups/Serotypes, in HIV-Infected and -Uninfected Adults with Pneumococcal Bacteremia

Among 1022 adults with either pneumococcal bacteremia or meningitis, 85.5% of women and 74.7% of men were infected with human immunodeficiency virus (HIV). A multivariable regression analysis found more pediatric serogroups/serotypes (odds ratio [OR], 1.59 [95% confidence interval [CI], 1.18-2.15]) and more penicillin-nonsusceptible strains (OR, 1.65 [95% CI, 1.06-2.59]) in women than in men; it was also found that bacteremic women were more likely to be infected with HIV (OR, 1.85 [95% CI, 1.26-2.71]) and to be younger (OR, 1.72 [95% CI, 1.25-2.36]) than were men. Thus, conjugate pneumococcal vaccination of children may reduce, in particular, both antibiotic resistance and the burden of conjugate vaccine serotype pneumococcal disease in young, HIV-infected women.

Antimicrobial susceptibility of methicillin-resistant Staphylococcus aureus isolates from South Africa

OBJECTIVE Trends in the antibiotic susceptibility of methicillin-resistant Staphylococcus aureus (MRSA) are regularly investigated in many countries, but minimal countrywide data are available for South Africa. The aim of this study was to describe the antibiotic susceptibility patterns of MRSA isolates collected in South Africa. DESIGN Susceptibility testing of 248 MRSA isolates collected from 15 National Health Laboratory Services (NHLS) and 8 private laboratories against 17 antibiotics was performed using the disc diffusion method. Demographic data were collected and correlated with antibiotic resistance patterns. RESULTS Antibiotic resistance of MRSA to erythromycin, tetracycline, trimethoprim/sulfamethoxazole, gentamicin and ciprofloxacin ranged between 55% and 78%, while all isolates were susceptible to teicoplanin, linezolid, vancomycin and quinopristin/dalfopristin. A significant difference in the resistance pattern of the isolates towards certain antimicrobial agents was identified among adults and children, as well as between isolates collected from the private and NHLS laboratories. CONCLUSION This is the first extensive report on the antimicrobial susceptibilities of South African MRSA isolates. These data can assist treatment decisions and form a baseline for further surveillance.

Staphylococcus aureus bacteraemia in Gauteng academic hospitals, South Africa

INTRODUCTION Methicillin-resistant Staphylococcus aureus (MRSA) infections are responsible for longer hospital stays, increased hospital costs, and poorer outcomes compared to methicillin-sensitive S. aureus (MSSA) infections. We aimed to describe the epidemiology of S. aureus bacteraemia (SAB) and to determine factors associated with MRSA infection in South Africa. METHODS Cases of SAB were reported from September 2012 to September 2013 from three sentinel sites. A case was defined as the isolation of S. aureus from a blood culture during a 21-day period. Detailed clinical information was collected. Multivariable logistic regression was done to determine factors associated with MRSA infection and mortality. RESULTS There were 442 cases of SAB reported; antimicrobial susceptibility testing was performed on 240 isolates (54%). Thirty-six percent (86/240) of cases had an MRSA infection. A longer hospital stay before positive specimen collection (odds ratio (OR) 1.08, 95% confidence interval (CI) 1.02-1.13, p=0.004), hospitalization in the last year (OR 15.7, 95% CI 2.5-99.5, p=0.003), HIV infection (OR 4.9, 95% CI 1.05-22.90, p=0.044), and antibiotic use in the previous 2 months (OR 0.1, 95% CI 0.01-0.68, p=0.022) were independent predictors of MRSA. Older age, and in particular age 25-44 years (OR 22.2, 95% CI 2.7-185.5, p=0.004, compared to those aged<5 years), was the only independent predictor of mortality amongst cases with SAB. MRSA isolates were non-susceptible to more antimicrobial agents compared to MSSA isolates. CONCLUSIONS HIV infection was an independent risk factor for MRSA infection. The selection of appropriate empirical antimicrobial treatment is essential in patients with MRSA infections because of non-susceptibility to many other antimicrobial classes.

Nosocomial Outbreak of New Delhi Metallo-β-Lactamase-1-Producing Gram-Negative Bacteria in South Africa: A Case-Control Study.

Objective New Delhi metallo-β-lactamase (NDM)-producing Gram-negative bacteria have spread globally and pose a significant public health threat. There is a need to better define risk factors and outcomes of NDM-1 clinical infection. We assessed risk factors for nosocomial infection with NDM-1-producers and associated in-hospital mortality. Methods A matched case-control study was conducted during a nosocomial outbreak of NDM-1-producers in an adult intensive care unit (ICU) in South Africa. All patients from whom NDM-1-producers were identified were considered (n=105). Cases included patients admitted during the study period in whom NDM-1 producing Gram-negative bacteria were isolated from clinical specimens collected ≥48 hours after admission, and where surveillance definitions for healthcare-associated infections were met. Controls were matched for age, sex, date of hospital admission and intensive-care admission. Conditional logistic regression was used to identify risk factors for NDM-1 clinical infection and associated in-hospital mortality. Findings 38 cases and 68 controls were included. Klebsiella pneumoniae was the most common NDM-1-producer (28/38, 74%). Cases had longer mean hospital stays (44.0 vs. 13.3 days; P < 0.001) and ICU stays (32.5 vs. 8.3 days; P < 0.001). Adjusting for co-morbid disease, the in-hospital mortality of cases was significantly higher than controls (55.3% vs. 14.7%; AOR, 11.29; P < 0.001). Higher Charlson co-morbidity index score (5.2 vs. 4.1; AOR, 1.59; P = 0.005), mechanical ventilation days (7.47 vs. 0.94 days; AOR, 1.32; P = 0.003) and piperacillin/tazobactam exposure (11.03 vs. 1.05 doses; AOR, 1.08; P = 0.013) were identified as risk factors on multivariate analysis. Cases had a significantly higher likelihood of in-hospital mortality when the NDM-1-producer was Klebsiella pneumoniae (AOR, 16.57; P = 0.007), or when they had a bloodstream infection (AOR, 8.84; P = 0.041). Conclusion NDM-1 infection is associated with significant in-hospital mortality. Risk factors for hospital-associated infection include the presence of co-morbid disease, mechanical ventilation and piperacillin/tazobactam exposure.

Prevalence and trends of Staphylococcus aureus bacteraemia in hospitalized patients in South Africa, 2010 to 2012 : laboratory-based surveillance mapping of antimicrobial resistance and molecular epidemiology

Introduction We aimed to obtain an in-depth understanding on recent antimicrobial resistance trends and molecular epidemiology trends of S. aureus bacteraemia (SAB). Methods Thirteen academic centres in South Africa were included from June 2010 until July 2012. S. aureus susceptibility testing was performed on the MicroScan Walkaway. Real-time PCR using the LightCycler 480 II was done for mecA and nuc. SCCmec and spa-typing were finalized with conventional PCR. We selected one isolate per common spa type per province for multilocus sequence typing (MLST). Results S. aureus from 2709 patients were included, and 1231 (46%) were resistant to methicillin, with a significant decline over the three-year period (p-value = 0.003). Geographical distribution of MRSA was significantly higher in Gauteng compared to the other provinces (P<0.001). Children <5 years were significantly associated with MRSA with higher rates compared to all other age groups (P = 0.01). The most prevalent SCCmec type was SCCmec type III (531 [41%]) followed by type IV (402 [31%]). Spa-typing discovered 47 different spa-types. The five (87%) most common spa-types were t037, t1257, t045, t064 and t012. Based on MLST, the commonest was ST612 clonal complex (CC8) (n = 7) followed by ST5 (CC5) (n = 4), ST36 (CC30) (n = 4) and ST239 (CC8) (n = 3). Conclusions MRSA rate is high in South Africa. Majority of the isolates were classified as SCCmec type III (41%) and type IV (31%), which are typically associated with hospital and community- acquired infections, respectively. Overall, this study reveals the presence of a variety of hospital-acquired MRSA clones in South Africa dominance of few clones, spa 037 and 1257. Monitoring trends in resistance and molecular typing is recommended to detect changing epidemiological trends in AMR patterns of SAB.

Antimicrobial susceptibility testing in predicting the presence of carbapenemase genes in Enterobacteriaceae in South Africa

BackgroundCarbapenem-resistant Enterobacteriaceae (CRE) is a concern in South Africa and worldwide. It is therefore important that these organisms be accurately identified for infection prevention control purposes.MethodIn this study 1193 suspected CREs from 46 laboratories from seven provinces in South Africa were assessed to confirm the prevalence of carbapenemase genes from our referral diagnostic isolates for the period 2012 to 2015. We compared the antimicrobial susceptibility testing method used in the reference laboratory to the polymerase chain reaction (PCR) which is used as the gold standard. Organism identification and antimicrobial susceptibility testing were performed using automated systems and DNA was extracted using a crude boiling method. The presence of carbapenemase-producing genes (blaNDM,blaKPC,blaOXA-48&variants,blaGES,blaIMP and blaVIM) was screened for using a multiplex real-time PCR.ResultsSixty-eight percent (n = 812) of the isolates harboured a carbapenemase-producing gene; the three most common genes included: blaNDM,blaOXA-48&variants and blaVIM. Majority of the carbapenemase producing Enterobacteriaceae (CPE) isolates were Klebsiella species (71 %). The Microscan® Walkaway system used for the screening of carbapenemase production was 98 % sensitive with a minimal inhibitory concentration (MIC) breakpoint of less than 0.5 as susceptible for ertapenem and a low specificity (13 %).ConclusionFrom this study we can conclude that carbapenemase-producing Enterobacteriaceae is increasing in South Africa and the use of phenotypic methods for detection of CPEs showed good sensitivity but lacked specificity.

Serum 1,3-βD-Glucan assay in the diagnosis of invasive fungal disease in neonates

Invasive fungal disease is a significant cause of morbidity and mortality in the neonate. The current study aims to assess the 1, 3-βD-Glucan (BG) assay in a prospective analysis in neonates with suspected fungaemia. A multicentre, prospective cohort study was conducted in Johannesburg, South Africa. The study included 72 neonates with clinically suspected late onset sepsis who were at high risk of fungaemia. A BG assay was performed on each patient and correlated with a sepsis classification based on the full blood count, C-reactive protein and blood culture results as no fungaemia, possible fungaemia, probable fungaemia or definite fungaemia. Sensitivity and specificity of the BG assay at levels of 60 pg/mL are 73.2% and 71.0% respectively and at levels of 80 pg/mL are 70.7% and 77.4% respectively. Positive and negative predictive values at 60 pg/mL are 76.9% and 66.7% respectively and at 80 pg/mL are 80.6% and 66.7% respectively. The area under the receiver operating curve is 0.753. The BG assay is a useful adjunct to the diagnosis of invasive fungal disease in neonates. It does, however, need to be considered in the context of the clinical picture and supplementary laboratory investigations.

Clinical practice - the role of appropriate diagnostic testing in acute respiratory tract infections : an antibiotic stewardship strategy to minimise diagnostic uncertainty in primary care : in practice

Antibiotic resistance has increased worldwide to the extent that it is now regarded as a global public health crisis. Interventions to reduce excessive antibiotic prescribing to patients can reduce resistance and improve microbiological and clinical outcomes. Therefore, although improving outpatient antibiotic use is crucial, few data are provided on the key interventional components and the effectiveness of antibiotic stewardship in the primary care setting, in South Africa. The reasons driving the excessive prescription of antibiotics in the community are multifactorial but, perhaps most importantly, the overlapping clinical features of viral and bacterial infections dramatically reduce the ability of GPs to distinguish which patients would benefit from an antibiotic or not. As a consequence, the need for tools to reduce diagnostic uncertainty is critical. In this regard, besides clinical algorithms, a consensus of collaborators in European and UK consortia recently provided guidance for the use of C-reactive protein point-of-care testing in outpatients presenting with acute respiratory tract infections (ARTIs) and/or acute cough, if it is not clear after proper clinical assessment whether antibiotics should be prescribed or not. A targeted application of stewardship principles, including diagnostic stewardship as described in this review, to the ambulatory setting has the potential to affect the most common indications for systemic antibiotic use, in that the majority (80%) of antibiotic use occurs in the community, with ARTIs the most common indication.

The Epidemiology of Meningitis among Adults in a South African Province with a High HIV Prevalence, 2009-2012.

Introduction Meningitis is a major cause of mortality in southern Africa. We aimed to describe the aetiologies and frequencies of laboratory-confirmed fungal and bacterial meningitis among adults in a South African province with an 11% HIV prevalence, over 4 years. Methods We conducted a retrospective, observational study of secondary laboratory data, extracted on all cerebrospinal fluid (CSF) specimens submitted to public-sector laboratories in Gauteng province from 2009 through 2012. We calculated cause-specific incidence rates in the general and HIV-infected populations and used Poisson regression to determine if trends were significant. Results We identified 11,891 (10.7%) incident cases of meningitis from 110,885 CSF specimens. Cryptococcal meningitis, tuberculous meningitis and pneumococcal meningitis accounted for 62.3% (n = 7,406), 24.6% (n = 2,928) and 10.1% (n = 1,197) of cases over the four-year period. The overall incidence (cases per 100,000 persons) of cryptococcal meningitis declined by 23% from 24.4 in 2009 to 18.7 in 2012 (p <0.001) and decreased by 19% among HIV-infected persons from 178.2 to 144.7 (p <0.001). Tuberculous meningitis decreased by 40% from 11.3 in 2009 to 6.8 in 2012 (p <0.001) and decreased by 36% among HIV-infected persons from 54.4 to 34.9 (p <0.001). Pneumococcal meningitis decreased by 41% from 4.2 in 2009 to 2.5 in 2012 (p <0.001) and decreased by 38% among HIV-infected persons from 28.0 to 17.5 (p <0.001). Among cases of other bacterial meningitis (248/11,891, 2.1%), Neisseria meningitidis (n = 93), Escherichia coli (n = 72) and Haemophilus influenzae (n = 20) were the most common organisms identified. Conclusions In this high HIV-prevalence province, cryptococcal meningitis was the leading cause of laboratory-confirmed meningitis among adults. Over a 4-year period, there was a significant decrease in incidence of cryptococcal, tuberculous and pneumococcal meningitis. This coincided with expansion of the national antiretroviral treatment programme, enhanced tuberculosis control programme and routine childhood immunisation with pneumococcal conjugate vaccines.

Molecular detection of carbapenemase-producing genes in referral Enterobacteriaceae in South Africa: A short report

Molecular confirmation of carbapenemase-producing Enterobacteriaceae (CPE) was introduced in South Africa (SA) at the end of 2011. We report on the detection of these resistance genes based on referral isolates. Enterobacteriaceae with non-susceptibility to any of the carbapenems according to defined criteria for antimicrobial susceptibility testing results were sent to a reference laboratory. A proportion of isolates had limited demographic, epidemiological and clinical data available. Organism identification was reconfirmed using reference laboratory methods, and the presence of carbapenemases was confirmed with a real-time polymerase chain reaction. We analysed 1 503 significant isolates received for confirmation from the National Health Laboratory Service and some private laboratories during 2012 - 2015 and confirmed one or more carbapenemase-producing genes in 68% of isolates, the most common organism being Klebsiella pneumoniae (60%). The most common carbapenemase genes were blaNDM, followed by blaOXA-48 and its variants. BlaOXA-48 and its variants demonstrated non-susceptibility to ertapenem in 89% of the isolates when analysed by the phenotypic method, and to ceftazidime in 34%. Overall, the detection rate for carbapenemases in K. pneumoniae blood isolates in the public sector was 1.9% during the 4-year period. This report indicates the presence of CPE in SA, and it is important for all healthcare workers to be aware of this major public health threat so that infection prevention and control measures can be implemented to prevent the spread of CPE in healthcare facilities.