Browsing by Author "Nuttall, James"

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    A descriptive study of vancomycin usage at Red Cross War Memorial Children's Hospital, Cape Town
    (2023) Greybe, Leonore; Nuttall, James; Eley Brian
    Background: Antimicrobial stewardship principles guide the clinical use of vancomycin, but paediatric vancomycin prescribing practices have not been evaluated in South Africa. Objectives: To document the use, prescribing practices and monitoring of intravenous vancomycin and the spectrum of bacteria isolated on microbiological culture in children treated with intravenous vancomycin during a 12-month period at Red Cross War Memorial Children's Hospital (RCWMCH). Methods: A retrospective audit of intravenous vancomycin use in children admitted to RCWMCH during 2019. Results: All 158 vancomycin prescription episodes for 143 children were included. Overall usage of intravenous vancomycin was 63 days of therapy/1000 patient days (IQR 38–72). The median starting dose was 15 mg/kg/dose (IQR 14 ̶ 15) and median daily dose was 45 mg/kg/day (IQR 43–60). Vancomycin was prescribed as empiric (127/158, 80%) and directed (31/158, 20%) treatment. The median duration of treatment for the directed group was longer than the empiric group (p=0.001). Only 65/98 (66%) episodes where vancomycin treatment exceeded three days had vancomycin serum trough concentrations performed, and only 16/65 (25%) of these samples were obtained before the fourth dose. Prolonged antibiotic treatment of 14 days or more was not associated with gram positive bacteria on culture (OR 1.02, 95% CI 0.17 ̶ 4.2). Conclusion: Prolonged empiric treatment and inappropriate vancomycin monitoring were problems associated with vancomycin prescriptions. Contribution: Our study identified multiple opportunities for improved vancomycin prescribing and monitoring. Further research and implementation of improved prescribing practices could contribute to the preservation of vancomycin as an effective antibiotic.
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    A ten-year review of ESBL and non-ESBL Escherichia Coli Bloodstream infections among children at a tertiary referral hospital in South Africa
    (2019) Malande, Oliver Ombeva; Eley, Brian; Nuttall, James
    Introduction: Bloodstream infection (BSI) is an important cause of morbidity and mortality in children (1). There are few descriptions of Escherichia coli (E. coli) BSI in children, particularly in Africa, yet E. coli is increasing in importance as a cause of antibiotic-resistant infection in paediatric settings. Methods: In this retrospective, descriptive study aspects of E. coli BSI epidemiology are described over a 10-year period including incidence risk, risk factors for extended spectrum β-lactamase (ESBL)- producing E. coli BSI, antibiotic susceptibility of the bacterial isolates and outcome including risk factors for severe disease. Results: There were 583 new E. coli BSI episodes among 217,483 admissions, an overall incidence risk of 2.7 events/1,000 hospital admissions. Of 455 of these E. coli BSI episodes that were analysed, 136 (29.9%) were caused by ESBL-producing isolates. Risk factors for ESBL-producing E. coli BSI included hospitalization in the 28-day period preceding E. coli BSI episodes and having an underlying chronic illness other than HIV infection at the time of the E. coli BSI. None of the E. coli isolates were resistant to carbapenems or colistin. The mortality rate was 5.9% and admission to the intensive care unit was required in 12.3% of BSI episodes. Predictors of severe disease included age less than 1 month, hospitalization in the 28-day period preceding E. coli BSI and BSI without a definable focus. Conclusions: These findings extend our understanding of E. coli BSI in a sub-Saharan African setting, provide useful information that can guide empiric treatment choices for community- and hospitalacquired BSI and help inform prevention strategies.
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    Adherence to antiretroviral therapy in young children in Cape Town, South Africa, measured by medication return and caregiver self-report: a prospective cohort study
    (BioMed Central Ltd, 2008) Davies, Mary-Ann; Boulle, Andrew; Fakir, Tanzeem; Nuttall, James; Eley, Brian
    BACKGROUND:Antiretroviral therapy (ART) dramatically improves outcomes for children in Africa; however excellent adherence is required for treatment success. This study describes the utility of different measures of adherence in detecting lapses in infants and young children in Cape Town, South Africa. METHODS: In a prospective cohort of 122 HIV-infected children commenced on ART, adherence was measured monthly during the first year of treatment by medication return (MR) for both syrups and tablets/capsules. A questionnaire was administered to caregivers after 3 months of treatment to assess experience with giving medication and self-reported adherence. Viral and immune response to treatment were assessed at the end of one year and associations with measured adherence determined. RESULTS: Medication was returned for 115/122 (94%) children with median age (IQR) of 37 (16 - 61) months. Ninety-one (79%) children achieved annual average MR adherence [greater than or equal to] 90%. This was an important covariate associated with viral suppression after adjustment for disease severity (OR = 5.5 [95%CI: 0.8-35.6], p = 0.075), however was not associated with immunological response to ART. By 3 months on ART, 13 (10%) children had deceased and 11 (10%) were lost to follow-up. Questionnaires were completed by 87/98 (90%) of caregivers of those who remained in care. Sensitivity of poor reported adherence (missing [greater than or equal to] 1 dose in the previous 3 days) for MR adherence <90% was only 31.8% (95% CI: 10.7% - 53.0%). Caregivers of 33/87 (38.4%) children reported difficulties with giving medication, most commonly poor palatability (21.8%). Independent socio-demographic predictors of MR adherence [greater than or equal to] 90% were secondary education of caregivers (OR = 4.49; 95%CI: 1.10 - 18.24) and access to water and electricity (OR = 2.65; 95%CI: 0.93 - 7.55). Taking ritonavir was negatively associated with MR adherence [greater than or equal to] 90% (OR = 0.37; 95%CI: 0.13 - 1.02). CONCLUSION: Excellent adherence to ART is possible in African infants and young children and the relatively simple low technology measure of adherence by MR strongly predicts viral response. Better socio-economic status and more palatable regimens are associated with better adherence.
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    Antiretroviral treatment for children
    (Health and Medical Publishing Group, 2006) Eley, Brian; Davies, Mary-Ann; Apolles, Patti; Cowburn, Carol; Buys, Heloise; Zampoli, Marco; Finlayson, Heather; King, Spasina; Nuttall, James
    Objective: To describe the response of children during their first year on highly active antiretroviral therapy (HAART). Design: Retrospective, descriptive. Setting. Tertiary, referral hospital. Subjects: All HIV-infected children commenced on HAART from 1 August 2002 until 31 December 2004. Outcome measures: Children were retrospectively restaged using the WHO 4-stage clinical classification and CDC immunological staging system. After commencing HAART, patients were assessed at monthly intervals for the first 6 months and thereafter mostly 3-monthly. Baseline and 6- monthly CD4 counts and viral loads were performed. Results. Of 409 children commenced on HAART, 50.6% were < 2 years old, 62.7% had severe clinical disease and 76.6% had severe immune suppression. After 1 year, 65.8% were alive and continued HAART at the hospital, 11.2% had been transferred to another antiretroviral site, 15.4% had died, 4.6% were lost to follow-up and treatment had been discontinued in 2.9%. Kaplan-Meier survival estimate for 407 children at 1 year was 84% (95% confidence interval (CI) 80 - 87%). On multivariate analysis, survival was adversely affected in children with WHO stage 4 v. stage 2 and 3 disease (adjusted hazard ratio (HR): 5.26 (95% CI 2.25 - 12.32), p = 0.000), age < 12 months (adjusted HR: 2.46 (95% CI 1.48 - 4.09), p = 0.001) and CD4 absolute count (per 100 cell increase) (adjusted HR: 0.93 (95% CI 0.88 - 0.98), p = 0.013). In a separate multivariate model including only children with an initial viral load (N = 367), viral load r 1 million copies/ml (adjusted HR: 1.84 (95% CI 1.03 - 3.29)) and taking a protease inhibitor (PI)-based regimen (adjusted HR: 2.25 (95% CI 1.10 - 4.61)) were additionally independently associated with poorer survival; however, young age was not a significant predictor of mortality, after adjusting for viral load (p = 0.119). After 1 year of HAART 184/264 (69.7%) of children had a viral load < 400 copies/ml. Comparative analysis showed significant improvements in growth, immunological status and virological control. Conclusion: HAART can improve the health of many HIVinfected children with advanced disease, including those aged less than 2 years in resource-limited settings.
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    Bloodstream infections at a tertiary level paediatric hospital in South Africa
    (BioMed Central, 2017-12-06) Lochan, Harsha; Pillay, Vashini; Bamford, Colleen; Nuttall, James; Eley, Brian
    Background: Bloodstream infection (BSI) in children causes significant morbidity and mortality. There are few studies describing the epidemiology of BSI in South African children. Methods: A retrospective descriptive cohort study was conducted at a paediatric referral hospital in Cape Town, South Africa. The National Health Laboratory Service (NHLS) microbiology database was accessed to identify positive blood culture specimens during the period 2011–2012. Demographic and clinical details, antimicrobial management and patient outcome information were extracted from medical and laboratory records. Antibiotic susceptibility results of identified organisms were obtained from the NHLS database. Results: Of the 693 unique bacterial and fungal BSI episodes identified during the study period, 248 (35.8%) were community-acquired (CA), 371 (53.5%) hospital-acquired (HA) and 74 (10.7%) healthcare-associated (HCA). The overall risk was 6.7 BSI episodes per 1000 admissions. Escherichia coli, Staphylococcus aureus and Streptococcus pneumoniae were the most frequent causes of CA-BSI and Klebsiella pneumoniae, Acinetobacter baumanii and S. aureus were most commonly isolated in HA-BSI. On multivariable analysis, severe underweight, severe anaemia at the time of BSI, admission in the ICU at the time of BSI, and requiring ICU admission after BSI was diagnosed were significantly associated with 14-day mortality. Conclusion: This study adds to the limited literature describing BSI in children in Africa. Further studies are required to understand the impact that BSI has on the paediatric population in sub-Saharan Africa.
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    Candida bloodstream infection among children hospitalized in three public sector hospitals in the Metro West region of Cape Town, South Africa
    (2022) Gebremicael, Mulugeta Naizgi; Eley, Brian; Nuttall, James
    Introduction Candida bloodstream infection (BSI) causes appreciable mortality in children. There are few studies describing the epidemiology of Candida BSI in children living in the Western Cape province of South Africa. Methods A retrospective descriptive study was conducted at three public sector hospitals in Cape Town from January 2015 to December 2019. Demographic, clinical, antifungal management and patient outcome data were obtained by medical record review. Candida species and antifungal susceptibility results were extracted from the National Health Laboratory Service microbiology database Results Of the 97 Candida BSI episodes identified during the study period, 48/97 (49.5%) were C. albicans, 49/97 (50.5%) non-C. albicans species. The overall incidence risk was 0.84 Candida BSI episodes per 1000 admissions at Red Cross War Memorial Children's Hospital. Of the 77 Candida BSI episodes with available clinical information, median age (interquartile range) at the time of BSI was 6.8 (1.3-24.7) months, 46.8% were associated with moderate or severe underweight-for-age and vasopressor therapy was administered to 22 (28.6%) participants. Fluconazole resistance was documented among 25% and 0% of non-C. albicans and C. albicans isolates respectively. All Candida isolates tested were susceptible to amphotericin B and the echinocandins. The mortality rate within 30 days of BSI diagnosis was 17.3% (13/75). On multivariable analysis, concomitant bacterial infection during Candida BSI was associated with 30-day mortality, adjusted OR 5.7, 95% confidence interval: 1.4-24.0. Conclusion The study adds to the limited number of studies describing paediatric Candida BSI in sub Saharan Africa. Concomitant bacterial infection was associated with 30-day mortality.
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    Colonisation with extended spectrum beta-lactamase producing and carbapenem-resistant enterobacterales in children admitted to a paediatric referral hospital in South Africa
    (2020) Ogunbosi, Babatunde Oluwatosin; Eley, Brian; Nuttall, James
    Introduction: There are few studies describing colonisation with extended spectrum beta-lactamase-producing Enterobacterales (ESBL-PE) and carbapenem-resistant Enterobacterales (CRE) among children in subSaharan Africa. Colonisation often precedes infection and multi-drug-resistant Enterobacterales are important causes of invasive infection. Methods: In this prospective cross-sectional study, conducted between April and June 2017, 200 children in a tertiary academic hospital were screened by rectal swab for EBSL-PE and CRE. The resistance-conferring genes were identified using polymerase chain reaction technology. Risk factors for colonisation were also evaluated. Results: Overall, 48% (96/200) of the children were colonised with at least one ESBL-PE, 8 of these with 2 ESBLPE, and one with a CRE (0.5%, 1/200). Common colonising ESBL-PE were Klebsiella pneumoniae (62.5%, 65/104) and Escherichia coli (34.6%, 36/104). The most frequent ESBL-conferring gene was blaCTX-M in 95% (76/80) of the isolates. No resistance- conferring gene was identified in the CRE isolate (Enterobacter cloacae). Most of the Klebsiella pneumoniae isolates were susceptible to piperacillin/tazobactam (86.2%) and amikacin (63.9%). Similarly, 94.4% and 97.2% of the Escherichia coli isolates were susceptible to piperacillin/tazobactam and amikacin, respectively. Hospitalisation for more than 7 days before study enrolment was associated with ESBL-PE colonisation. Conclusion: Approximately half of hospitalised children in this study were colonised with ESBL-PE. This highlights the need for improved infection prevention and control practices to limit the dissemination of these microorganisms.
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    Epidemiology of Staphylococcus aureus bacteraemia at a tertiary children's hospital in Cape Town, South Africa
    (Public Library of Science, 2013) Naidoo, Reené; Nuttall, James; Whitelaw, Andrew; Eley, Brian
    BACKGROUND: Staphylococcus aureus is an important pathogen in paediatric patients with bloodstream infections. The epidemiology of S. aureus bacteraemia, however, has not been well documented in children in South Africa. METHODS: A retrospective study was conducted at a children's hospital in Cape Town, South Africa, to investigate the epidemiology of S. aureus bacteraemia from 2007-2011. The incidence, clinical presentation, risk factors, management and outcomes of methicillin sensitive S. aureus (MSSA) and methicillin resistant S. aureus (MRSA) bacteraemia were compared. RESULTS: Over the five year study period, 365 episodes of S. aureus bacteraemia were identified. The annual incidence was 3.28 cases per 1000 hospital admissions. MRSA was responsible for 26% of S. aureus bacteraemia and 72% of nosocomial infections. Only six possible cases of community-acquired MRSA infections were described. MSSA bacteraemia was more likely to present as pulmonary and bone or joint infections, while bacteraemia without a source was the most common presentation with MRSA.  Infants, children with malnutrition, and residents of long-term care facilities were at highest risk for MRSA bacteraemia. The overall case fatality rate for S. aureus bacteraemia was 8.8% over five years, with MRSA being the only significant risk factor for mortality. CONCLUSION: The incidence of S. aureus bacteraemia and MRSA bacteraemia in children has remained stable over the past five years. MRSA is a predominantly nosocomial pathogen in children with S. aureus bacteraemia in Cape Town, South Africa.
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    Epidemiology of Staphylococcus aureus bacteraemia at a tertiary children's hospital in Cape Town, South Africa
    (2012) Naidoo, Reené; Eley, Brian; Nuttall, James
    Includes abstract. Includes bibliographical references.
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    HIV-infected infants born to women who tested HIV-negative during pregnancy
    (2004) Nuttall, James; Eley, Brian; Honikman, Simone
    The prevention of mother-to-child transmission (PMTCT) programme in the Western Cape is said to have achieved 100% coverage.1 This implies that all pregnant women who attend an antenatal health care facility in the public sector are offered voluntary counselling and testing (VCT). Uptake varies but has been reported to be as high as 90% in the Guguletu district.1 Currently, women who test HIV-positive qualify for the nevirapine-based PMTCT programme. Transmission rates below 10% have been achieved in some health districts (Médecins sans Frontières — unpublished research). Mothers of several perinatally infected infants recently diagnosed in our institution have indicated that they tested HIV-negative during their pregnancy. In some cases we have verified their statements with clinical and laboratory documentation. There is a need to determine the frequency of this phenonomen. Pregnant women are encouraged to book at their nearest antenatal clinic before 5 months’ gestation, although this frequently does not occur. We are concerned about women who do book early and test HIV-negative. Some may be in the ‘window period’ of the infection or become infected from a sexual partner during the latter stages of pregnancy. At present, there is no provision within the PMTCT programme for repeat HIV testing during pregnancy. Some women may, therefore, be denied the benefits of prevention measures including counselling on infant feeding options.
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    Initial experience of a public sector antiretroviral treatment programme for HIV-infected children and their infected parents
    (2004) Eley, Brian; Nuttall, James; Davies, Mary-Ann; Smith, Lara; Cowburn, Carol; Buys, Heloise; Hussey, Gregory
    Objective. To describe the initial experience of treating HIVinfected children and their infected parents with antiretroviral therapy. Design. Prospective, cohort study. Setting. Tertiary, referral hospital. Patients. HIV-infected children and their parents. Methods. This report focuses on the early response of children to highly active antiretroviral therapy (HAART). Children were followed up at 4-weekly intervals. Monitoring included initial and yearly viral load measurements, baseline and 6- monthly CD4 counts and 4-weekly adherence checks. Results. Between August 2002 and June 2003, 80 children were enrolled in the programme, representing a follow-up period of 23.9 patient-years. Seventy-five children had severe clinical disease, severe immune suppression, or a combination of the two. The response of children who had received HAART for ≥ 6 months (N = 17) was assessed. There was no change in mass z-score (p = 0.11) or length z-score (p = 0.37), but a significant increase in CD4 percentage (p < 0.0001) during the first 6 months of therapy. Six-month viral loads were available for 12 children. There was a significant drop in viral load (p = 0.001) and 9 achieved undetectable levels by 6 months. Most children achieved ≥ 85% adherence. By June 2002, 67 children (84%) were relatively well, 1 had B-cell lymphoma, 7 (8.8%) had died, 4 (5%) were lost to follow-up and 1 was withdrawn from the programme. Of 57 children who completed 3 months of HAART, 12 were admitted a total of 17 times for infectious complications. There were no severe drug reactions. Three of 7 mothers on HAART received treatment through the programme. Conclusion. These initial results suggest that many HIVinfected children in the public sector will benefit from antiretroviral therapy. However, both ambulatory and inpatient facilities are required to manage children on HAART comprehensively
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    It is time to consider third-line options in antiretroviral-experienced paediatric patients?
    (BioMed Central Ltd, 2011) van Zyl, Gert; Rabie, Helena; Nuttall, James; Cotton, Mark
    BACKGROUND: The historic use of full-dose ritonavir as part of an unboosted protease inhibitor (PI)-based antiretroviral therapy regimen in some South African children contributes to the frequent accumulation of major PI resistance mutations. METHODS: In order to describe the prevalence of major PI resistance in children failing antiretroviral therapy and to investigate the clinical, immunological and virological outcomes in children with PI resistance, we conducted a cross-sectional study, with a nested case series, following up those children with major PI resistance. The setting was public health sector antiretroviral clinics in the Western Cape province of South Africa, and the subjects were children failing antiretroviral therapy. The following outcome measures were investigated: CD4 count, viral load and resistance mutations. RESULTS: Fourteen (17%) of 82 patients, referred from tertiary hospitals, had major PI resistance. All these patients were exposed to regimens that included ritonavir as a single PI. Immune reconstitution and clinical benefit were achieved when using a lopinavir/ritonavir-based treatment regimen in these children with prior PI resistance. At first HIV-1 viral load follow up after initial resistance testing (n = 11), only one patient had a viral load of less than 400 copies/ml; at a subsequent follow up (n = 9), the viral loads of five patients were less than 400 copies/ml. Patients retained on LPV/r had lower viral loads than those switched to a non-nucleoside reverse transcriptase inhibitor (NNRTI). However, two of three patients with follow-up resistance tests accumulated additional PI resistance. CONCLUSIONS: In children with pre-existing PI resistance, although initially effective, the long-term durability of a lopinavir/ritonavir-based treatment regimen can be compromised by the accumulation of resistance mutations. Furthermore, a second-line NNRTI regimen is often not durable in these patients. As genotypic resistance testing and third-line treatment regimens are costly and limited in availability, we propose eligibility criteria to identify patients with high risk for resistance and guidance on drug selection for children who would benefit from third-line therapy.
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    Prevalence and Determinants of Vitamin D Deficiency in 1825 Cape Town Primary Schoolchildren: A Cross-Sectional Study
    (Multidisciplinary Digital Publishing Institute, 2022-03-16) Middelkoop, Keren; Walker, Neil; Stewart, Justine; Delport, Carmen; Jolliffe, David A.; Nuttall, James; Coussens, Anna K.; Naude, Celeste E.; Tang, Jonathan C. Y.; Fraser, William D.; Wilkinson, Robert J.; Bekker, Linda-Gail; Martineau, Adrian R.
    Vitamin D deficiency (25-hydroxyvitamin D[25(OH)D] <50 nmol/L) is common among adults in Cape Town, South Africa, but studies investigating vitamin D status of children in this setting are lacking. We conducted a cross-sectional study to determine the prevalence and determinants of vitamin D deficiency in 1825 Cape Town schoolchildren aged 6–11 years. Prevalence of vitamin D deficiency was 7.6% (95% Confidence Interval [CI] 6.5% to 8.9%). Determinants of vitamin D deficiency included month of sampling (adjusted odds ratio [aOR] for July–September vs. January–March 10.69, 95% CI 5.02 to 22.77; aOR for October–December vs. January–March 6.73, 95% CI 2.82 to 16.08), older age (aOR 1.25 per increasing year, 95% CI: 1.01–1.53) and higher body mass index (BMI; aOR 1.24 per unit increase in BMI-for-age Z-score, 95% CI: 1.03–1.49). In a subset of 370 participants in whom parathyroid hormone (PTH) concentrations were measured; these were inversely related to serum 25(OH)D concentrations (p < 0.001). However, no association between participants with hyperparathyroidism (PTH >6.9 pmol/L) and vitamin D deficiency was seen (p = 0.42). In conclusion, we report that season is the major determinant of vitamin D status among Cape Town primary schoolchildren, with prevalence of vitamin D deficiency ranging from 1.4% in January–March to 22.8% in July–September.
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    Pseudomonas aeruginosa bloodstream infection at a tertiary referral hospital for children
    (2020-10-07) Dame, Joycelyn A; Beylis, Natalie; Nuttall, James; Eley, Brian
    Background This study describes the disease burden, clinical characteristics, antibiotic management, impact of multidrug resistance and outcome of Pseudomonas aeruginosa bloodstream infection (PABSI) among children admitted to a tertiary referral hospital for children in Cape Town, South Africa. Methods A retrospective descriptive study was conducted at a paediatric referral hospital in Cape Town, South Africa. Demographic and clinical details, antibiotic management and patient outcome information were extracted from medical and laboratory records. Antibiotic susceptibility results of identified organisms were obtained from the National Health Laboratory Service database. Results The incidence risk of PABSI was 5.4 (95% CI: 4.34–6.54) PABSI episodes / 10,000 hospital admissions and the most common presenting feature was respiratory distress, 34/91 (37.4%). Overall, 69/91 (75.8%) of the PA isolates were susceptible to all antipseudomonal antibiotic classes evaluated. Fifty (54.9%) of the PABSI episodes were treated with appropriate empiric antibiotic therapy. The mortality rate was 24.2% and in multivariable analysis, empiric antibiotic therapy to which PA isolates were not susceptible, infections present on admission, and not being in the intensive care unit at the time that PABSI was diagnosed were significantly associated with 14-day mortality. Conclusions PABSI caused appreciable mortality, however, appropriate empiric antibiotic therapy was associated with reduced 14-day mortality.
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    Pseudomonas aeruginosa bloomstream infection at a tertiary referral hospital for children
    (2020) Dame, Joycelyn Assimeng; Eley, Brian; Nuttall, James
    Introduction This study describes the disease burden, clinical characteristics, antibiotic management, impact of multidrug resistance and outcome of Pseudomonas aeruginosa bloodstream infection (PABSI) among children admitted to a tertiary referral hospital for children in Cape Town, South Africa. Methods A retrospective descriptive study was conducted at a paediatric referral hospital in Cape Town, South Africa. Demographic and clinical details, antibiotic management and patient outcome information were extracted from medical and laboratory records. Antibiotic susceptibility results of identified organisms were obtained from the National Health Laboratory Service database. Results The overall incidence risk of PABSI was 5.4 PABSI episodes / 10,000 hospital admissions and the most common presenting feature was respiratory distress, 34/91 (37%). Overall, 69/91 (76%) of the PA isolates were susceptible to all antipseudomonal antibiotic classes evaluated. Fifty (55%) of the PABSI episodes were treated with appropriate empiric antibiotic therapy. The mortality rate was 24% and in multivariable analysis, empiric antibiotic therapy to which PA isolate was not susceptible to, infections present on admission, and not being in the intensive care unit at the time that PABSI was diagnosed were significantly associated with 14-day mortality. Conclusion The study provided insight into factors associated with PABSI in a tertiary hospital in SubSaharan Africa. Empiric antipseudomonal antibiotic therapy was associated with a decrease in 14-day mortality.
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    Urinary tract infection in children at Victoria Hospital, a district hospital in Cape Town, South Africa
    (2023) Shepherd, Danielle; Nuttall, James
    Background: Urinary tract infections (UTI) are one of the most common bacterial infections in childhood, with the potential to cause acute and long-term complications. Diagnosing UTI in children is often challenging due to non-specific symptoms, difficulty in collecting sterile specimens, and culture results only becoming available after 24-48 hours, necessitating initiation of empiric antibiotic therapy. Recent data on the epidemiology and antibiotic susceptibility profile of community-acquired bacterial UTI in children in Cape Town is lacking. Objectives: To describe the clinical profile and organisms including antibiotic susceptibility testing (AST) results in children <10 years of age with community-acquired, culture-confirmed bacterial UTI attending Victoria Hospital, Cape Town. To compare the AST findings with the current South African (SA) Hospital Level Paediatric Standard Treatment Guidelines (STG) which recommend oral or parenteral amoxicillin/clavulanic acid as first-line empiric treatment for children with UTI, with ceftriaxone included as an alternative for neonates or acutely ill infants. Methods: A retrospective review of medical records and laboratory results of children <10 years of age who had a urine specimen submitted for culture and AST to the National Health Laboratory Service from Victoria Hospital between 1 February 2016 – 31 July 2019 was performed. The study definition of a culture-confirmed bacterial UTI is modified from the SA STG guidelines: (1) any culture from a suprapubic aspirate, (2) culture of >104 colony forming units (CFU)/mL of a single organism from a catheter urine specimen, (3) culture of >105 CFU/mL of a single organism from a mid-stream clean catch specimen or if the urine sampling technique was not indicated in the laboratory or medical records. Descriptive statistics were used to analyse the data. Results: From 528 urine specimens submitted, 89 specimens met the study definition of bacterial UTI and were included in the microbiological analysis. Seventy-eight children with available medical records were included in the demographic and clinical analysis. Median (interquartile range) age was 25 (0;117) months and 58% were female. One or more nonspecific features of systemic illness were reported in 65% of children, and 51% had at least one symptom specific to the urinary system. Enterobacterales accounted for 99% of the organisms cultured (85% were Escherichia coli) and their susceptibility was amoxicillin/clavulanic acid (58%), cefuroxime (84%), third and fourth generation cephalosporins (88%), ciprofloxacin (94%), gentamicin (86%) and nitrofurantoin (90%). Eleven (12%) isolates were extended spectrum beta lactamase-producing organisms but no carbapenem-resistant organisms were isolated. Conclusion: Although this study did not evaluate clinical outcomes of children, the AST finding that only 58% of Enterobacterales isolates were susceptible to the recommended empiric treatment with amoxicillin/clavulanic acid raises the concern that children may not be receiving appropriate treatment for UTI. Further research is needed on the antibiotic susceptibility profile and clinical outcome of children treated for UTI in order to inform appropriate empiric antibiotic treatment recommendations.
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    Xpert MTB/RIF Ultra and mycobacterial culture in routine clinical practice at a Tertiary Paediatric Hospital
    (2021) Enimil, Anthony Kwame; Eley, Brian; Nuttall, James
    Introduction World Health Organization approved the use of Xpert MTB/RIF Ultra (Ultra) in children due to quick turn-around time, improved yield over smear microscopy, and ability to detect rifampicin resistance despite culture being the “gold standard”. This study reviewed published literature on current childhood tuberculosis diagnostic modalities. It also retrospectively compared demographic, clinical, and radiological features of children with confirmed and unconfirmed PTB, reviewed criteria for microbiologically unconfirmed PTB, and assessed incremental microbiological yield on second and third Ultra and/or mycobacterial culture results in routine clinical care at a tertiary paediatric hospital. Method For the review on childhood TB diagnostic modalities, PubMed was searched using Boolean terms OR/AND between childhood tuberculosis and words such as diagnosis, polymerase chain reaction, molecular, histology, imaging, and cultures. All abstracts were read after which selected articles that met the objectives of the thesis were fully reviewed and referenced appropriately. The retrospective study was conducted in children (0 to 13 years) treated for Pulmonary TB (PTB) between 1 February 2018 and 31 January 2019 and who had at least one respiratory specimen investigated by Ultra and/or mycobacterial culture before TB treatment was commenced. Relevant demographic, clinical information, tuberculin skin test results and laboratory results were abstracted from paper-based medical records and electronic database. Baseline chest radiographic findings were obtained from the radiology digital imaging database. All data was entered anonymously into a Microsoft Excel spreadsheet and exported to R-statistical software for statistical analysis. Descriptive and inferential statistics were used in the analysis. Incremental yield of Ultra and/or mycobacterial cultures on sequential respiratory specimens was determined. Results Ultra is an important diagnostic method for confirming TB in children even though mycobacterial culture, molecular, and histology tests are also available. Other modalities such as imaging and immunologic tests support the diagnosis of microbiologically unconfirmed TB. 174 children with PTB ± EPTB were included in the retrospective study. The median age was 2.5 years. Tuberculosis was microbiologically confirmed in 93 (53.4%). Yield on Ultra in first respiratory specimens was 39.1%. When the results of Ultra and mycobacterial culture on first respiratory specimens were combined, 47.1% (82/174) had microbiologically confirmed TB. Microcytic anaemia and pulmonary pathology were more common in confirmed TB. Of 81 children with microbiologically unconfirmed TB, 31 (38.3%) met a consensus definition of unconfirmed intrathoracic TB formulated by an international expert committee. In the subset of children (n=70) who were screened by Ultra on two sequential respiratory specimens, the incremental yield was 30.3%. When the results of Ultra and mycobacterial culture were combined the incremental yield in children who had 2 sequential respiratory specimens tested was 24.4% and 3.1% on Ultra and mycobacterial culture, respectively. Conclusion Ultra and/or mycobacterial culture on single respiratory specimens resulted in high microbiological yield. Ultra on second sequential respiratory specimens increased microbiological confirmation. The value of additional Ultra and/or mycobacterial culture testing in routine clinical practice requires further study.