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This study describes ceftazidime-avibactam use in 17 young children from a resource-constrained country, where intra-abdominal infection was common. All-cause mortality was 53%. Earlier initiation, dose optimization, recording infusion times, and reviewing the need for additional antibiotics were identified as easy-to-implement-antimicrobial-stewardship interventions. [ABSTRACT FROM AUTHOR]

Background: Sexually transmitted infections are among the most commonly occurring infections globally, with countries in sub-Saharan Africa exhibiting disproportionately higher prevalence rates. Numerous reports indicate the need for accurate detection, epidemiological characterisation, and appropriate management of these infections. This prospective observational laboratory study sought to determine the occurrence of STI, using a validated molecular assay as a diagnostic and surveillance tool in our setting. Methods: Urogenital swabs from symptomatic and asymptomatic patients, submitted to the National Health Laboratory Service, at Groote Schuur Hospital, from 04 August 2021–03 February 2022, for routine microbiological investigations, were subjected to the Allplex™ STI Essential Assay (Seegene Inc, South Korea) to determine the distribution of STI pathogens in our setting. This multiplex assay includes C. trachomatis, Mycoplasma genitalium, Mycoplasma hominis, N. gonorrhoeae, Trichomonas vaginalis, Ureaplasma parvum, and Ureaplasma urealyticum. Correlations between detected organisms and participant age and clinical indications for testing were determined using Stata® software. Results: A total of 148 urogenital swabs (91.2% from women) were included in the analysis, of which 56/148 (37.84%) were from symptomatic patients. Up to 83.8% of the samples tested positive for ≥1 organism, with all seven target organisms detected in at least one sample. Ureaplasma parvum was the most common organism detected, followed by N. gonorrhoeae, M. hominis, U. urealyticum, T. vaginalis, C. trachomatis, with M. genitalium being the least detected. All 25 samples submitted for routine antenatal Group B Streptococcal screening were positive for at least one STI organism, and one sample from sexual non-accidental injury tested positive for five different organisms. Conclusions: STIs comprise a variety of organisms in our setting, with many patients exhibiting coinfection with multiple organisms. This suggests the need for a critical evaluation of current syndromic testing and treatment guidelines so as to stem inadvertent spread of STI organisms and the development of resistance. The use of molecular testing methods may improve detection, especially in resource limited settings, providing speedy results, and thus allowing for guided therapy in only infected patients. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial stewardship principles guide the clinical use of antimicrobials, including 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). Method: A retrospective audit of intravenous vancomycin use in children admitted to RCWMCH during 2019 was performed. Results: All 158 vancomycin prescription episodes for 143 children were included. Overall usage of intravenous vancomycin was 63 days of therapy per 1000 patient days (interquartile range [IQR]: 38–72). The median starting dose was 15 mg/kg per dose (IQR: 14–15) and median daily dose was 45 mg/kg per 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 (7 days) was longer than the empiric group (4 days) (p = 0.001). Vancomycin serum trough concentrations were performed in 65/98 (66%) episodes where vancomycin treatment exceeded 3 days, with only 16/65 (25%) of these samples obtained before the fourth dose. Prolonged antibiotic treatment of 14 days or more was not associated with Gram-positive bacteria on culture (odds ratio [OR]: 1.02, 95% confidence interval [CI]: 0.17–4.2). Conclusion: Dosing errors, prolonged empiric treatment and inappropriate vancomycin monitoring were problems associated with vancomycin prescriptions. Contribution: The 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. [ABSTRACT FROM AUTHOR]

We report the first case of Balamuthia mandrillaris granulomatous amoebic encephalitis definitively acquired in Africa. Our case emphasizes initial nonspecific dermatological features, delays in confirmation of the diagnosis, difficulties accessing recommended medication, and uncertainty about optimal treatment of a disease with a frequently fatal outcome. [ABSTRACT FROM AUTHOR]

The increased incidence and absence of antibiotic treatment options for New Delhi metalloβ-lactamase (NDM)-producing carbapenem-resistant Enterobacterales (CRE) infection are concerning. Recent reports have highlighted NDM-producing Serratia marcescens, as a specific concern, as it is an organism which is intrinsically resistant to colistin. In this study, a descriptive analysis of NDM-producing CRE infections was performed at the Red Cross War Memorial Children’s Hospital. [ABSTRACT FROM AUTHOR]

Antibiotic stewardship of hospital-acquired infections because of difficult-to-treat resistant (DTR) Gram-negative bacteria is a global challenge. Their increasing prevalence in South Africa has required a shift in prescribing in recent years towards colistin, an antibiotic of last resort. High toxicity levels and developing resistance to colistin are narrowing treatment options further. Recently, two new β-lactam/β-lactamase inhibitor combinations, ceftazidime-avibactam and ceftolozane-tazobactam were registered in South Africa, bringing hope of new options for management of these life-threatening infections. However, with increased use in the private sector, increasing levels of resistance to ceftazidimeavibactam are already being witnessed, putting their long-term viability as treatment options of last resort, in jeopardy. This review focuses on how these two vital new antibiotics should be stewarded within a framework that recognises the resistance mechanisms currently predominant in South Africa’s multi-drug and DTR Gram-negative bacteria. Moreover, the withholding of their use for resistant infections that can be treated with currently available antibiotics is a critical part of stewardship, if these antibiotics are to be conserved in the long term. [ABSTRACT FROM AUTHOR]

Culture remains the diagnostic standard for Streptococcus pneumoniae bacteraemia but is limited by time to identification, prior antibiotics and bacterial autolysis. Culture-independent methods for detecting S. pneumoniae include PCR and antigen tests. We evaluated an antigen test on blood culture broth for the rapid detection of S. pneumoniae bacteraemia. We collected 212 signal-positive blood cultures, with gram-positive cocci in pairs, chains or with uncertain morphology. The BinaxNOW S. pneumoniae urinary antigen test, Gram stain, culture and lytA PCR were performed on all samples. Diagnostic accuracy of the antigen test and Gram stain with gram-positive cocci in pairs were compared with culture, polymerase chain reaction (PCR) and the composite of culture and PCR. Streptococcus pneumoniae was isolated in 26% of samples, 66% cultured other gram-positive organisms and 8% of samples had no growth. Sensitivity and negative predictive values of the antigen test were 100%, specificity and positive predictive values were 87% – 88% and 76% – 81%, but increased to 93% – 96% and 96% – 98% when applied to subsets with gram-positive cocci in pairs, or history compatible with respiratory illness or meningitis. Sensitivity (69% – 75%) and specificity (81%) of Gram stain (gram-positive cocci in pairs) were lower than the antigen test even when applied to the same subsets. Accurate and rapid diagnosis of S. pneumoniae bacteraemia is challenging. Specificity of this antigen test is limited by cross-reactivity with other gram-positive organisms, but could be improved if Gram stain morphology and clinical history are available. The antigen test is a useful adjunct for rapid diagnosis of S. pneumoniae bacteraemia. [ABSTRACT FROM AUTHOR]

Antibiotic stewardship of hospital-acquired infections because of difficult-to-treat resistant (DTR) Gram-negative bacteria is a global challenge. Their increasing prevalence in South Africa has required a shift in prescribing in recent years towards colistin, an antibiotic of last resort. High toxicity levels and developing resistance to colistin are narrowing treatment options further. Recently, two new β-lactam/β-lactamase inhibitor combinations, ceftazidime-avibactam and ceftolozane-tazobactam were registered in South Africa, bringing hope of new options for management of these life-threatening infections. However, with increased use in the private sector, increasing levels of resistance to ceftazidime-avibactam are already being witnessed, putting their long-term viability as treatment options of last resort, in jeopardy. This review focuses on how these two vital new antibiotics should be stewarded within a framework that recognises the resistance mechanisms currently predominant in South Africa's multi-drug and DTR Gram-negative bacteria. Moreover, the withholding of their use for resistant infections that can be treated with currently available antibiotics is a critical part of stewardship, if these antibiotics are to be conserved in the long term., Competing Interests: The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article., (© 2022. The Authors.)

In vitro MICs and in vivo pharmacodynamics of ceftazidime and cefepime human-simulated regimens (HSR) against modified carbapenem inactivation method (mCIM)-positive Pseudomonas aeruginosa isolates harboring different OXA-10-like subtypes were described. The murine thigh model assessed ceftazidime (2 g every 8 h [q8h] HSR) and cefepime (2 g and 1 g q8h HSR). Phenotypes were similar despite possessing OXA-10-like subtypes with differing spectra. Ceftazidime produced ≥1-log 10 killing in all isolates. Cefepime activity was dose dependent and MIC driven. This approach may be useful in assessing the implications of β-lactamase variants.