Medical Microbiology

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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.
Antibody responses to vaccination among South African HIV-exposed and unexposed uninfected infants during the first 2 years of life
(American Society for Microbiology, 2013-01) Reikie, Brian A.; Naidoo, Shalena; Ruck, Candice E.; Slogrove, Amy L.; De Beer, Corena; La Grange, Heleen; Adams, Rozanne C. M.; Ho, Kevin; Smolen, Kinga; Speert, David P.; Cotton, Mark F.; Preiser, Wolfgang; Esser, Monika; Kollmann, Tobias R.
HIV-exposed but uninfected (HEU) infants born to HIV-infected mothers from areas in the world with a high burden of infectious disease suffer higher infectious morbidity and mortality than their HIV unexposed uninfected (HUU) peers. Vaccination provides protection from infection. The possibility exists that altered response to vaccination contributes to the higher rate of infection in HEU than in HUU infants. While short-term, cross-sectional studies support this notion, it is unclear whether or not HEU infants develop long-term protective immune responses following theWHOextended program on immunization (EPI). Vaccine-specific antibody responses were compared between HEU and HUU infants from 2 weeks until 2 years of age in a longitudinal South African cohort. Total IgG and antibodies specific for Bordetella pertussis, Haemophilus influenzae type b (Hib), tetanus toxoid, hepatitis B virus (HepB), and measles virus were measured at multiple time points throughout the first 2 years of life. Prevaccine antibodies (maternal antibodies passively acquired) specific for tetanus were lower in HEU than in HUU infants, while prevaccine antibodies to HepB were higher in HEU than in HUU infants. Both groups responded similarly to tetanus, Hib, and HepB vaccination. HEU demonstrated stronger pertussis vaccine responses, developing protective titers 1 year earlier than HUU patients, and maintained higher anti-tetanus titers at 24 months of age. Vaccine-induced antibodies to measles virus were similar in both groups at all time points. Our results suggest that the current EPI vaccination program as practiced in South Africa leads to the development of vaccine-specific antibody responses that are equivalent in HEU and HUU infants. However, our data also suggest that a large fraction of both HEU and HUU South African infants have antibody titers for several infectious threats that remain below the level of protection for much of their first 2 years of life.
An appraisal of the uricult dip slide method in the diagnosis of urinary infections
(HMPG, 1973-05) Finlayson, M. H.; Coates, J. K.; Brede, H. D.; Mitchell, P.
Uricult dip slide urine cultures were compared with standard laboratory plate cultures. Good agreement of bacterial counts was obtained after incubation at 37°C but not at room temperature. Tests of therapeutic activity of various drugs on the commoner organisms producing urinary infections, were done. The results suggested that such tests had no positive value. Uricult dip slides should be of value as a suitable transport and diagnostic medium for the diagnosis of urinary tract infections.
Association between clinical and environmental factors and the gut microbiota profiles in young South African children
(Nature Research (part of Springer Nature), 2021) Nel Van Zyl, Kristien; Whitelaw, Andrew C.; Hesseling, Anneke C.; Seddon, James A.; Demers, Anne‑Marie; Newton‑Foot, Mae
ENGLISH ABSTRACT: Differences in the microbiota in populations over age and geographical locations complicate cross-study comparisons, and it is therefore essential to describe the baseline or control microbiota in each population. This includes the determination of the influence of demographic, clinical and environmental factors on the microbiota in a setting, and elucidates possible bias introduced by these factors, prior to further investigations. Little is known about the microbiota of children in South Africa after infancy. We provide a detailed description of the gut microbiota profiles of children from urban Cape Town and describe the influences of various clinical and environmental factors in different age groups during the first 5 years of life. Prevotella was the most common genus identified in the participants, and after infancy, the gut bacteria were dominated by Firmicutes and Bacteroidetes. In this setting, children exposed to antibiotics and indoor cooking fires were at the most risk for dysbiosis, showing significant losses in gut bacterial diversity.
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.
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.
The association between pathogen factors and clinical outcomes in patients with Staphylococcus aureus bacteraemia in a tertiary hospital, Cape Town
(Elsevier on behalf of International Society for Infectious Diseases, 2019-11-29) Abdulgadera, Shima M.; Van Rijswijk, Amike; Whitelawa, Andrew; Newton-Foota, 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 d-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.
B-cell and T-cell activation in South African HIV-1-positive non-Hodgkin’s lymphoma patients
(Medpharm Publications, 2018) Flepisi, Brian T.; Bouic, Patrick; Sissolak, Gerhard; Rosenkranz, Bernd
Background: Altered immune mechanisms play a critical role in the pathogenesis of non-Hodgkin’s lymphoma (NHL). HIV-1 (HIV) infection is associated with a state of excessive T-cell activation, which can lead to increased T-cell turnover and lymph node fibrosis. Objectives: This study aimed to determine the serum levels of circulating B-cell activation markers, and the expression of T-cell activation and regulatory markers in HIV-positive NHL patients. Method: The serum levels of circulating soluble(s) sCD20, sCD23, sCD27, sCD30 and sCD44 molecules, all of which are biomarkers of B-cell activation, were determined by enzyme-linked immunosorbent assays (ELISA), while biomarkers of T-cell activation (CD8+CD38+) and regulation (FoxP3) were determined by flow cytometry in 141 subjects who were divided into five groups: Combination antiretroviral therapy (ART)-naïve HIV-positive patients; ART-treated HIV-positive patients; HIV-negative NHL patients; HIV-positive NHL patients on ART; and healthy controls. Results: HIV-positive NHL patients had significantly higher serum levels of sCD20, sCD23, sCD30 and sCD44 than HIV-negative NHL patients, while all five biomarkers were significantly elevated in HIV-positive NHL patients when compared with ART-treated HIV-positive patients. HIV-positive NHL patients had higher CD8+CD38+ and lower FoxP3 expression than HIV-negative NHL and ART-treated HIV-positive patients. Conclusion: B-cell activation is increased in HIV-positive NHL patients and is associated with reduced regulatory T-cell populations and increased CD8+ T-cell activation.
Bacterial infection, antibiotic use and COVID-19 : lessons from the intensive care unit
(Health & Medical Publishing Group, 2021-04-14) Moolla, M. S.; Reddy, K.; Fwemba, I.; Nyasulu, P. S.; Taljaard, J. J.; Parker, A.; Lalla, U.; Koegelenberg, C. F. N.; Allwood, B. W.
Background. Empirical broad-spectrum antibiotics are frequently prescribed to patients with severe COVID-19, motivated by concern about bacterial coinfection. There is no evidence of benefit from such a strategy, while the dangers of inappropriate antibiotics are well described. Objectives. To investigate the frequency, profile and related outcomes of infections by bacterial pathogens in patients admitted to an intensive care unit (ICU) with severe COVID-19 pneumonia. Methods. This was a prospective, descriptive study in a dedicated COVID-19 ICU in Cape Town, South Africa, involving all adult patients admitted to the ICU with confirmed COVID-19 pneumonia between 26 March and 31 August 2020. We collected data on patient comorbidities, laboratory results, antibiotic treatment, duration of admission and in-hospital outcome. Results. We included 363 patients, who collectively had 1 199 blood cultures, 308 tracheal aspirates and 317 urine cultures performed. We found positive cultures for pathogens in 20 patients (5.5%) within the first 48 hours of ICU admission, while 73 additional patients (20.1%) had positive cultures later during their stay. The most frequently isolated pathogens at all sites were Acinetobacter baumannii (n=54), Klebsiella species (n=13) and coagulase-negative staphylococci (n=9). Length of ICU stay (p<0.001) and intubation (p<0.001) were associated with positive cultures on multivariate analysis. Disease severity (p=0.5), early antibiotic use (p=0.5), diabetes mellitus (p=0.1) and HIV (p=0.9) were not associated with positive cultures. Positive cultures, particularly for tracheal aspirates (p<0.05), were associated with longer ICU length of stay and mortality. Early empirical antibiotic use was not associated with mortality (odds ratio 2.5; 95% confidence interval 0.95 - 6.81). Conclusions. Bacterial coinfection was uncommon in patients at the time of admission to the ICU with severe COVID-19. Avoiding early empirical antibiotic therapy is therefore reasonable. Strategies to avoid coinfection and outbreaks in hospital, such as infection prevention and control, as well as the strict use of personal protective equipment, are important to improve outcomes.
Bedaquiline, moxifloxacin, pretomanid, and pyrazinamide during the first 8 weeks of treatment of patients with drug-susceptible or drug-resistant pulmonary tuberculosis: a multicentre, open-label, partially randomised, phase 2b trial
(Elsevier, 2019) Tweed, Conor D.; Dawson, Rodney; Burger, Divan A.; Conradie, Almari; Crook, Angela M.; Mendel, Carl M.; Conradie, Francesca; Diacon, Andreas H.; Ntinginya, Nyanda E.; Everitt, Daniel E.; Haraka, Frederick; Li, Mengchun; Van Niekerk, Christo H.; Okwera, Alphonse; Rassool, Mohammed S.; Reither, Klaus; Sebe, Modulakgotla A.; Staples, Suzanne; Variava, Ebrahim; Spigelman, Melvin
Background: New anti-tuberculosis regimens that are shorter, simpler, and less toxic than those that are currently available are needed as part of the global effort to address the tuberculosis epidemic. We aimed to investigate the bactericidal activity and safety profile of combinations of bedaquiline, pretomanid, moxifloxacin, and pyrazinamide in the first 8 weeks of treatment of pulmonary tuberculosis. Methods: In this multicentre, open-label, partially randomised, phase 2b trial, we prospectively recruited patients with drug-susceptible or rifampicin-resistant pulmonary tuberculosis from seven sites in South Africa, two in Tanzania, and one in Uganda. Patients aged 18 years or older with sputum smear grade 1+ or higher were eligible for enrolment, and a molecular assay (GeneXpert or MTBDR plus ) was used to confirm the diagnosis of tuberculosis and to distinguish between drug-susceptible and rifampicin-resistant tuberculosis. Patients who were HIV positive with a baseline CD4 cell count of less than 100 cells per uL were excluded. Patients with drug-susceptible tuberculosis were randomly assigned (1:1:1) using numbered treatment packs with sequential allocation by the pharmacist to receive 56 days of treatment with standard tuberculosis therapy (oral isoniazid, rifampicin, pyrazinamide, and ethambutol; HRZE), or pretomanid (oral 200 mg daily) and pyrazinamide (oral 1500 mg daily) with either oral bedaquiline 400 mg daily on days 1–14 then 200 mg three times per week (B load PaZ) or oral bedaquiline 200 mg daily (B 200 PaZ). Patients with rifampicin-resistant tuberculosis received 56 days of the B 200 PaZ regimen plus moxifloxacin 400 mg daily (BPaMZ). All treatment groups were open label, and randomisation was not stratified. Patients, trial investigators and staff, pharmacists or dispensers, laboratory staff (with the exception of the mycobacteriology laboratory staff), sponsor staff, and applicable contract research organisations were not masked. The primary efficacy outcome was daily percentage change in time to sputum culture positivity (TTP) in liquid medium over days 0–56 in the drug-susceptible tuberculosis population, based on non-linear mixed-effects regression modelling of log 10 (TTP) over time. The efficacy analysis population contained patients who received at least one dose of medication and who had efficacy data available and had no major protocol violations. The safety population contained patients who received at least one dose of medication. This study is registered with ClinicalTrials.gov , NCT02193776 , and all patients have completed follow-up. Findings: Between Oct 24, 2014, and Dec 15, 2015, we enrolled 180 patients with drug-susceptible tuberculosis (59 were randomly assigned to B load PaZ, 60 to B 200 PaZ, and 61 to HRZE) and 60 patients with rifampicin-resistant tuberculosis. 57 patients in the B load PaZ group, 56 in the B 200 PaZ group, and 59 in the HRZE group were included in the primary analysis. B 200 PaZ produced the highest daily percentage change in TTP (5·17% [95% Bayesian credibility interval 4·61–5·77]), followed by B load PaZ (4·87% [4·31–5·47]) and HRZE group (4·04% [3·67–4·42]). The bactericidal activity in B 200 PaZ and B load PaZ groups versus that in the HRZE group was significantly different. Higher proportions of patients in the B load PaZ (six [10%] of 59) and B 200 PaZ (five [8%] of 60) groups discontinued the study drug than in the HRZE group (two [3%] of 61) because of adverse events. Liver enzyme elevations were the most common grade 3 or 4 adverse events and resulted in the withdrawal of ten patients (five [8%] in the B load PaZ group, three [5%] in the B 200 PaZ group, and two [3%] in the HRZE group). Serious treatment-related adverse events affected two (3%) patients in the B load PaZ group and one (2%) patient in the HRZE group. Seven (4%) patients with drug-susceptible tuberculosis died and four (7%) patients with rifampicin-resistant tuberculosis died. None of the deaths were considered to be related to treatment. Interpretation: B 200 PaZ is a promising regimen to treat patients with drug-susceptible tuberculosis. The bactericidal activity of both these regimens suggests that they have the potential to shorten treatment, and the simplified dosing schedule of B 200 PaZ could improve treatment adherence in the field. However, these findings must be investigated further in a phase 3 trial assessing treatment outcomes. Funding: TB Alliance, UK Department for International Development, Bill & Melinda Gates Foundation, US Agency for International Development, Directorate General for International Cooperation of the Netherlands, Irish Aid, Australia Department of Foreign Affairs and Trade, and the Federal Ministry for Education and Research of Germany.
Biofilm formation and adherence characteristics of an Elizabethkingia meningoseptica isolate from Oreochromis mossambicus
(BioMed Central, 2011-05-05) Jacobs, Anelet; Chenia, Hafizah Y.
ABSTRACT: Background. Elizabethkingia spp. are opportunistic pathogens often found associated with intravascular device-related bacteraemias and ventilator-associated pneumonia. Their ability to exist as biofilm structures has been alluded to but not extensively investigated. Methods. The ability of Elizabethkingia meningoseptica isolate CH2B from freshwater tilapia (Oreochromis mossambicus) and E. meningoseptica strain NCTC 10016T to adhere to abiotic surfaces was investigated using microtiter plate adherence assays following exposure to varying physico-chemical challenges. The role of cell-surface properties was investigated using hydrophobicity (bacterial adherence to hydrocarbons), autoaggregation and coaggregation assays. The role of extracellular components in adherence was determined using reversal or inhibition of coaggregation assays in conjunction with Listeria spp. isolates, while the role of cell-free supernatants, from diverse bacteria, in inducing enhanced adherence was investigated using microtitre plate assays. Biofilm architecture of isolate CH2B alone as well as in co-culture with Listeria monocytogenes was investigated using flow cells and microscopy. Results E. meningoseptica isolates CH2B and NCTC 10016T demonstrated stronger biofilm formation in nutrient-rich medium compared to nutrient-poor medium at both 21 and 37°C, respectively. Both isolates displayed a hydrophilic cell surface following the bacterial adherence to xylene assay. Varying autoaggregation and coaggregation indices were observed for the E. meningoseptica isolates. Coaggregation by isolate CH2B appeared to be strongest with foodborne pathogens like Enterococcus, Staphylococcus and Listeria spp. Partial inhibition of coaggregation was observed when isolate CH2B was treated with heat or protease exposure, suggesting the presence of heat-sensitive adhesins, although sugar treatment resulted in increased coaggregation and may be associated with a lactose-associated lectin or capsule-mediated attachment. Conclusions. E. meningoseptica isolate CH2B and strain NCTC 10016T displayed a strong biofilm-forming phenotype which may play a role in its potential pathogenicity in both clinical and aquaculture environments. The ability of E. meningoseptica isolates to adhere to abiotic surfaces and form biofilm structures may result from the hydrophilic cell surface and multiple adhesins located around the cell.
Biofilm formation in invasive Staphylococcus aureus isolates is associated with the clonal lineage
(Stellenbosch : Stellenbosch University, 2016-01) Hoek, Kim G. P.; Harvey, Justin; Wasserman, Elizabeth; Naicker, Preneshni Rochelle; Karayem, Karayem
ENGLISH ABSTRACT: Objectives: The ability to form biofilms contributes significantly to the virulence of Staphylococcus aureus. Virulence factors may be associated with certain S. aureus lineages. However, the contribution of the genetic background of S. aureus to biofilm formation is poorly understood. This study investigated the association between the genetic background and the biofilm forming ability of clinical invasive S. aureus isolates. Secondary objectives included investigating any correlation with biofilm formation and methicillin resistance or the source of bacteraemia. Methods: The study was conducted at a 1300-bed tertiary hospital in Cape Town, South Africa. S. aureus isolates obtained from blood cultures between January 2010 and January 2012 were included. Genotypic characterization was performed by PFGE, spa typing, SCCmec typing and MLST. Thirty genotypically unique strains were assessed for phenotypic biofilm formation with the microtitre plate assay. All isolates were tested in triplicate and an average optical density, measured at a wavelength of 490nm, was determined. The biofilm forming ability of isolates with A490 > 0.17 was considered ‘weak positive’ and A490 > 0.34 ‘strong positive’. Isolates with A490 ≤ 0.17 were considered non-adherent. ANOVA with Bonferroni-adjusted post-hoc tests and t-tests were used for statistical analysis of the association between biofilm forming ability and strain characteristics. Results: Fifty seven percent of isolates were capable of forming biofilms. Weak biofilm formation occurred in 40% (n=12) and strong biofilm formation in 17% (n=5) of isolates. Thirteen (43%) of the isolates were classified as non-adherent. All 5 isolates capable of strong biofilm formation belong to one spa clonal complex (spa-CC 064). Strains from spa-CC 064 were capable of higher biofilm formation than other spa clonal complexes (p=0.00002). These 5 strains belonged to MLST CC5 and CC8. Biofilm formation did not correlate with methicillin resistance and was not related to the source of bacteraemia. Conclusion: Biofilm formation correlates with the spa clonal lineage in our population of invasive S. aureus strains. High biofilm formation was associated with spa-CC 064. MLST CC5 and CC8 strains are capable of strong biofilm formation.
Biomarkers of HIV-associated cancer
(Libertas Academica, 2014) Flepisi, Brian Thabile; Bouic, Patrick; Sissolak, Gerhard; Rosenkranz, Bernd
Cancer biomarkers have provided great opportunities for improving the management of cancer patients by enhancing the efficiency of early detection, diagnosis, and efficacy of treatment. Every cell type has a unique molecular signature, referred to as biomarkers, which are identifiable characteristics such as levels or activities of a myriad of genes, proteins, or other molecular features. Biomarkers can facilitate the molecular definition of cancer, provide information about the course of cancer, and predict response to chemotherapy. They offer the hope of early detection as well as tracking disease progression and recurrence. Current progress in the characterization of molecular genetics of HIV-associated cancers may form the basis for improved patient stratification and future targeted or individualized therapies. Biomarker use for cancer staging and personalization of therapy at the time of diagnosis could improve patient care. This review focuses on the relevance of biomarkers in the most common HIV-associated malignancies, namely, Kaposi sarcoma, non-Hodgkin’s lymphoma, and invasive cervical cancer.
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.
Carbapenemase-producing Enterobacteriaceae colonisation in adult inpatients : a point prevalence study
(AOSIS, 2019) Nel, Pieter; Paterson, Lauren A.; Hoffmann, Rena
Background: Infections caused by carbapenemase-producing Enterobacteriaceae (CPE) have been increasing worldwide in recent years, but data regarding the prevalence and clinical significance of CPE colonisation in South Africa is not well documented. Local private hospital groups have implemented routine screening programmes for selected high-risk patients as endorsed by the South African Society for Clinical Microbiology. This practice is not routinely performed in the public sector. Methods: A point prevalence study was performed at Tygerberg Hospital (TBH) by screening patients of all the adult inpatient wards to investigate the current prevalence of CPE colonisation. Common risk factors associated with CPE colonisation were also investigated. Results: From a total of 439 patient samples collected, only one patient was colonised with a Klebsiella pneumoniae organism harbouring blaNDM-1. The identified patient had none of the common risk factors associated with CPE colonisation. Conclusion: Based on these findings, screening for CPE colonisation in adults on admission to TBH is currently not recommended.
Carriage of colistin-resistant Gram-negative bacteria in children from communities in Cape Town (Tuberculosis child multidrug-resistant preventive therapy trial sub-study)
(AOSIS, 2021) Snyman, Yolandi; Whitelaw, Andrew C.; Maloba, Motlatji R. B.; Hesseling, Anneke C.; Newton-Foot, Mae
ENGLISH ABSTRACT: Colistin is a last-resort antibiotic against multidrug-resistant, Gram-negative bacteria. Colistin resistance has been described in the clinical settings in South Africa. However, information on carriage of these bacteria in communities is limited. This study investigated gastrointestinal carriage of colistin-resistant Escherichia coli and Klebsiella spp. and mcr genes in children from communities in Cape Town. Colistin-resistant E. coli was isolated from two participants (4%, 2/50), and mcr-1-mcr-9 genes were not detected. Gastrointestinal carriage of colistin-resistant Enterobacterales was rare; however, continuous extensive surveillance is necessary to determine the extent of carriage and its contribution to resistance observed in clinical settings.
Characterisation of mcr-4.3 in a colistin-resistant Acinetobacter nosocomialis clinical isolate from Cape Town, South Africa
(Elsevier, 2021) Snyman, Yolandi; Reuter, Sandra; Whitelaw, Andrew Christopher; Stein, Lisa; Maloba, Motlatji Reratilwe Bonnie; Newton-Foot, Mae
Objectives: Colistin resistance in Acinetobacter spp. is increasing, resulting in potentially untreatable noso- comial infections. Plasmid-mediated colistin resistance is of particular concern due to its low fitness cost and potential transferability to other bacterial strains and species. This study investigated the colistin resistance mechanism in a clinical Acinetobacter nosocomialis isolate from Cape Town, South Africa. Methods: A colistin-resistant A. nosocomialis isolate was identified from a blood culture in 2017. PCR and Illumina whole-genome sequencing (WGS) were performed to identify genes and mutations conferring resistance to colistin. Plasmid sequencing was performed on an Oxford Nanopore platform. mcr function- ality was assessed by broth microdilution after cloning the mcr gene into pET-48b( + ) and expressing it in SHuffle®T7 Escherichia coli and after curing the plasmid using 62.5 mg/L acridine orange. Results: The colistin minimum inhibitory concentration (MIC) of the A. nosocomialis isolate was 16 mg/L. The mcr-4.3 gene was detected by PCR and WGS. No other previously described colistin resistance mech- anism was found by WGS. The mcr-4.3 gene was identified on a 24 024-bp RepB plasmid (pCAC13a). Functionality studies showed that recombinant mcr-4.3 did not confer colistin resistance in E. coli. How- ever, plasmid curing of pCAC13a restored colistin susceptibility in A. nosocomialis . Conclusion: We describe the first detection of a plasmid-mediated mcr-4.3 gene encoding colistin re- sistance in A. nosocomialis and the first detection of mcr-4.3 in a clinical isolate in Africa. Recombinant expression of mcr-4.3 did not confer colistin resistance in E. coli , suggesting that its functionality may be RepB plasmid-dependent or species-specific.
Characterisation of mobile colistin resistance genes (mcr‑3 and mcr‑5) in river and storm water in regions of the Western Cape of South Africa
(BMC (part of Springer Nature), 2021) Snyman, Yolandi; Whitelaw, Andrew C.; Barnes, Jo M.; Maloba, Motlatji R. B.; Newton‑Foot, Mae
Background: Colistin is regarded as a last-resort antimicrobial against multi-drug resistant Gram-negative bacteria (GNB), therefore the dissemination of colistin resistance in the environment is of great concern. Horizontal transfer of mobile colistin resistance (mcr) genes to potential pathogens poses a serious problem. This study aimed to describe the presence of colistin resistant GNB and mcr genes in river and storm water in regions of the Western Cape. Methods: Water samples were collected from three rivers during May 2019 and January 2020 and two storm water samples were collected in November 2019. Colistin resistant GNB were cultured on MacConkey agar containing colistin and identified by MALDI-TOF. Colistin resistance was confirmed using broth microdilution (BMD). mcr-1-5 genes were detected by PCR performed directly on the water samples and on the colistin resistant isolates. mcr functionality was assessed by BMD after cloning the mcr genes into pET-48b(+) and expression in SHuffle T7 E. coli. Results: mcr-5.1 and various mcr-3 gene variants were detected in the Plankenburg-, Eerste- and Berg rivers and in storm water from Muizenberg, and only mcr-5.1 was detected in storm water from Fish Hoek. Colistin resistant GNB were isolated from all of the water sources. Aeromonas spp. were the most common colistin resistant organisms detected in the water sources; 25% (6/24) of colistin resistant Aeromonas spp. isolated from the Berg river contained novel mcr-3 variants; mcr-3.33 (n = 1), mcr-3.34 (n = 1) mcr-3.35 (n = 1) mcr-3.36 (n = 2) and mcr-3.37 (n = 1), which were confirmed to confer colistin resistance. Conclusions: The mcr-5.1 and mcr-3 colistin resistance gene variants were present in widely dispersed water sources in regions of the Western Cape. The mcr genes were only detected in water sampled downstream of and alongside communities, suggesting that their presence is driven by human influence/contamination. This is the first documentation of mcr-3 and mcr-5 gene variants in any setting in South Africa. Spill-over of these genes to communities could result in horizontal gene transfer to pathogenic bacteria, exacerbating the challenge of controlling multidrug resistant GNB infections.
Characteristics and outcome of children with juvenile dermatomyositis in Cape Town: a cross-sectional study
(BioMed Central, 2016-11-11) Okongo, Lawrence Owino; Esser, Monika; Wilmshurst, Jo; Scott, Christiaan
Background: Juvenile dermatomyositis (JDM) is a rare idiopathic inflammatory childhood myopathy of uncertain aetiology. The demographic and clinical presentation of JDM may differ by race and geographic regions. Few studies have described the characteristics of JDM patients from Africa. Methods: We conducted a retrospective observational study to determine clinical characteristics and outcomes of patients satisfying the Bohan and Peter criteria for probable JDM seen between 2004 and 2013 in three hospitals in Cape Town, South Africa. Results: Twenty five cases were identified: 16 female and 9 male; thirteen (52 %) were of indigenous African, eleven (44 %) mixed and one (4 %) European ancestry. The median ages at disease onset and diagnosis were 6.75 (range 2.0–9.7) and 7.9 (range 3.4–9.75) years respectively. Eleven patients had calcinosis while the mortality was 2/ 25 (8 %). Only 40 % of the patients had clinically inactive disease by PRINTO criteria (modified) at last review. There was no statistically significant difference in racial distribution (p-value = 1), age at disease onset (p-value = 0.87) and disease duration prior to treatment initiation (p-value = 0.75) between patients who had clinically active and inactive disease. Conclusion: The demographic characteristics of children with JDM were similar to that from most other regions of the world with female predominance and similar age at onset. Majority of the patients remained with clinically active disease, which put them at risk of further disease complications. Long term follow up and use of appropriate treatment guidelines may be indicated in management of JDM patients for optimum treatment outcomes.
Clonal expansion of colistin-resistant Acinetobacter baumannii isolates in Cape Town, South Africa
(Elsevier, 2020) Snyman, Yolandi; Whitelaw, Andrew Christopher; Reuter, Sandra; Dramowski, Angela; Maloba, Motlatji Reratilwe Bonnie; Newton-Foot, Mae
Objectives: To describe colistin-resistant Acinetobacter baumannii isolates in Cape Town, South Africa. Methods: A. baumannii isolates identified on Vitek 2 Advanced Expert System were collected from Tygerberg Hospital referral laboratory between 2016 and 2017. Colistin resistance was confirmed using broth microdilution and SensiTest. mcr-1–5 were detected using PCR and strain typing was performed by rep-PCR. Whole genome sequencing (WGS) was performed on a subset of isolates to identify chromosomal colistin resistance mechanisms and strain diversity using multilocus sequence typing (MLST) and pairwise single nucleotide polymorphism analyses. Results: Twenty-six colistin-resistant and six colistin-susceptible A. baumannii were collected separately based on Vitek susceptibility; 20/26 (77%) were confirmed colistin-resistant by broth microdilution. Four colistin-resistant isolates were isolated in 2016 and 16 in 2017, from five healthcare facilities. Thirteen colistin-resistant isolates and eight colistin-susceptible isolates were identical by rep-PCR and MLST (ST1), all from patients admitted to a tertiary hospital during 2017. The remaining colistin-resistant isolates were unrelated. Conclusions: An increase in colistin-resistant A. baumannii isolates from a tertiary hospital in 2017 appears to be clonal expansion of an emerging colistin-resistant strain. This strain was not detected in 2016 or from other hospitals. Identical colistin-susceptible isolates were also isolated, suggesting relatively recent acquisition of colistin resistance.

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