Developing an antibiogram for empiric antibiotic prescribing for adult non-spinal orthopaedic infections in a developing world setting.

PURPOSE: Empiric antibiotic strategies in the treatment of fracture-related infections, chronic osteomyelitis, prosthetic joint infection, and septic arthritis should be based on local microbiological antibiograms. This study aims to describe the microbiology and review the antibiogram profiles of bacterial isolates from patients undergoing surgical treatment for non-spinal orthopaedic infections, to identify the most appropriate empiric antibiotic strategy. METHODS: A retrospective review was performed of all cases of non-spinal orthopaedic infections treated surgically from 1 January 2018 to 31 December 2018. The National Health Laboratory Service microbiology database was used to identify all intra-operative microbiological specimens obtained from orthopaedic patients, and data were correlated with the orthopaedic surgical database. Cases were divided into fracture-related infections, chronic osteomyelitis, prosthetic joint infection, and septic arthritis. Antibiotic susceptibility data were used to predict the efficacy of different empiric antibiotic regimens. RESULTS: A total of 107 cases were included in the study; 184 organisms were cultured. Overall, the most common organism cultured was Staphylococcus aureus (25%) followed by Acinetobacter baumannii (9%), Enterococcus faecalis (7%) and Enterobacter cloacae (5%). Across all categories the oral antibiotic combination with the highest effectiveness (81%) would have been a combination of co-trimoxazole, ciprofloxacin and amoxicillin. The most effective intravenous antibiotic combination would have been either piperacillin-tazobactam, amikacin and vancomycin or meropenem and vancomycin; 90% of tested isolates were susceptible to either of these combinations. CONCLUSION: Antibiogram profiles can serve to guide to empiric antibiotic choice in the management of different categories of non-spinal orthopaedic infections.

Epidemiology of Gram-negative bacteria during coronavirus disease 2019. What is the real pandemic?

PURPOSE OF REVIEW: Bacterial infections play a key role in hospital outcomes during the coronavirus disease 2019 (COVID-19) pandemic. Nonetheless, the global impact on the epidemiology of Gram-negative bacteria (GNB) and antibiotic resistance has not been clearly established. RECENT FINDINGS: Multiple limitations exist in the current literature, in that substantial variability was observed with regard to methodology. Notwithstanding the heterogeneity, the evidence suggests that the COVID-19 pandemic had a substantial negative impact on global epidemiology with an increase in hospital-onset infections, associated with GNB. Similarly, an alarming increase in resistant GNB compared to prepandemic rates, was apparent. This was most evident for carbapenemase-producing Klebsiella pneumoniae (bloodstream infections), carbapenem-resistant Pseudomonas aeruginosa (ventilator-associated pneumonia), and carbapenem-resistant Acinetobacter baumannii (all infections). Significant variations were most apparent in the large, system-wide regional or national comparative assessments, vs. single-centre studies. Categorizing concurrent bacteria as co- or secondary-infections may be paramount to optimize standard of care. SUMMARY: The data from most studies signal the probability that COVID-19 accelerated resistance. However, multiple limitations intrinsic to interpretation of current COVID-19 data, prevents accurately quantifying collateral damage on the global epidemiology and antibiotic resistance amongst GNB. It is likely to be substantial and renewed efforts to limit further increases is warranted.

The role of multidrug and extensive-drug resistant Gam-negative bacteria in skin and soft tissue infections.

PURPOSE OF REVIEW: Whereas Staphylococcus aureus remains the leading cause of skin and soft tissue infections (SSTI), Gram-negative bacilli (GNB) are increasingly reported as a cause of monomicrobial or polymicrobial infections. This review examines the expanding role of GNB in SSTI and discusses the risks for and the frequency of multidrug-resistance (MDR) and extensive drug-resistance (XDR) and the implications with regard to outcome and therapy. RECENT FINDINGS: Although the global epidemiology and role of GNB in SSTIs have not been studied systematically, complicated SSTIs caused by resistant GNB are increasing particularly in vulnerable patients with long-standing infections, those in long-term care facilities, and those with a history of recent hospitalization or prior antibiotic therapy. Mixed infections also occur in up to 25% of SSTIs, and inappropriate therapy occurs in 40% of cases. Prompt identification of the causative pathogen requires that patients with SSTI be risk stratified according to the likelihood of resistance to enable early recognition and swift initiation of appropriate therapy. SUMMARY: For individual treatment decisions in SSTIs, institutional diagnostic and treatment algorithms based on local epidemiology and risk factors are pivotal to reducing the incidence of treatment failure and improving outcomes associated with resistant GNB.

Epidemiology of carbapenem-resistant Gram-negative infections globally.

PURPOSE OF REVIEW: The spread of carbapenem-resistant Gram-negative bacteria (GNB) with changes in institutional epidemiology continues to evolve worldwide. The purpose of this review is to evaluate new data with regard to the epidemiology, mechanisms of resistance and the impact of carbapenem resistance on mortality. RECENT FINDINGS: The rapid expansion of acquired carbapenem resistance is increasingly propagated by mobile genetic elements such as epidemic plasmids that transfer carbapenemase genes within and between GNB. The risk of acquisition of carbapenem-resistant Acinetobacter baumannii increases four-fold with carbapenem exposure and new meta-analyses have confirmed excess mortality associated with carbapenem-resistant Pseudomonas aeruginosa. Carbapenemase-producing Klebsiella pneumoniae, the most commonly encountered carbapenemase-producing Enterobacterales (CPE) and a major cause of high-mortality hospital-related infections, represents the most rapidly growing global threat. Carbapenem use in patients colonized with such genotypes, leads to an increase in CPE abundance in the gastrointestinal tract, which in turn increases the risk of blood-stream infections four-fold. SUMMARY: High-resistance rates in carbapenem-resistant GNB in many countries will inevitably complicate treatment of serious infections in vulnerable patient groups and should accelerate global attempts to overcome the impediments we face with regard to effective antimicrobial stewardship and infection prevention and control programs.

From guidelines to practice: a pharmacist-driven prospective audit and feedback improvement model for peri-operative antibiotic prophylaxis in 34 South African hospitals.

Background: Few data exist on the implementation of process measures to facilitate adherence to peri-operative antibiotic prophylaxis (PAP) guidelines in Africa. Objectives: To implement an improvement model for PAP utilizing existing resources, in order to achieve a reduction in surgical site infections (SSIs) across a heterogeneous group of 34 urban and rural South African hospitals. Methods: A pharmacist-driven, prospective audit and feedback strategy involving change management and improvement principles was utilized. This 2.5 year intervention involved a pre-implementation phase to test a PAP guideline and a 'toolkit' at pilot sites. Following antimicrobial stewardship committee and clinician endorsement, the model was introduced in all institutions and a survey of baseline SSI and compliance rates with four process measures (antibiotic choice, dose, administration time and duration) was performed. The post-implementation phase involved audit, intervention and monthly feedback to facilitate improvements in compliance. Results: For 70 weeks of standardized measurements and feedback, 24 206 surgical cases were reviewed. There was a significant improvement in compliance with all process measures (composite compliance) from 66.8% (95% CI 64.8-68.7) to 83.3% (95% CI 80.8-85.8), representing a 24.7% increase ( P < 0.0001). The SSI rate decreased by 19.7% from a mean group rate of 2.46 (95% CI 2.18-2.73) pre-intervention to 1.97 post-intervention (95% CI 1.79-2.15) ( P = 0.0029). Conclusions: The implementation of process improvement initiatives and principles targeted to institutional needs utilizing pharmacists can effectively improve PAP guideline compliance and sustainable patient outcomes.

Therapeutic drug monitoring: linezolid too?

Numerous factors interfere with the ability to achieve optimal pharmacokinetic and pharmacodynamic targets and this has been associated with greater mortality and lower cure rates. The recent study by Zoller and colleagues examining linezolid levels in critically ill patients emphasises this point. Their study is unique in the description of the intra-patient and inter-patient variability that occurs and in the degree to which therapy is inadequate; 63% of patients had insufficient levels and only 17% maintained optimal trough values (between 2 and 10 mg/l) throughout the 4 study days. Precisely why this result occurred is uncertain because albumin levels, free linezolid pharmacokinetics and the presence of augmented renal clearance were not recorded in the current study. The extent of this variability makes the case for therapeutic drug monitoring since an area under the inhibitory curve greater than 80 to 120 and the time above the minimum inhibitory concentration over the entire dosing interval strongly correlate with linezolid treatment efficacy. Accordingly, therapeutic drug monitoring where available or, if not available, alternative approaches to drug delivery such as continuous infusion or a dose increase--but particularly the former--may be the answer.

Emergence of OXA-48 and OXA-181 carbapenemases among Enterobacteriaceae in South Africa and evidence of in vivo selection of colistin resistance as a consequence of selective decontamination of the gastrointestinal tract.

This study reports on the emergence of OXA-48-like carbapenemases among isolates of Enterobacteriaceae in South Africa. In addition, the emergence during therapy of a colistin-resistant OXA-181-producing Klebsiella pneumoniae isolate was documented following selective digestive tract decontamination with oral colistin, which is therefore strongly discouraged.

Doxycycline post-exposure prophylaxis for sexually transmitted infections in South Africa.

South Africa has a large burden of bacterial sexually transmitted infections (STIs) with high rates among men who have sex with men (MSM). Randomised controlled trials have recently demonstrated high effectiveness of doxycycline post-exposure prophylaxis (PEP) for prevention of bacterial STIs in MSM, with 70% - 85% reductions in Chlamydia trachomatis infection and syphilis, and approximately 50% reduction in Neisseria gonorrhoeae infection. Doxycycline PEP was not demonstrated to be effective in reducing C. trachomatis and N. gonorrhoeae infection among Kenyan cisgender women. Although no worrisome trends in antimicrobial resistance (AMR) were observed in the trials, important concerns remain about doxycycline PEP and AMR development in STIs, other pathogens, commensals, and the microbiome. Tetracycline resistance in N. gonorrhoeae is already widespread in South Africa, but emergence of AMR in other STIs would be concerning. Larger sample sizes of doxycycline PEP users with longer follow-up time are needed to understand the impact that doxycycline PEP may have on AMR at individual and population level. In this opinion article, we weigh the benefits of doxycycline PEP for prevention of bacterial STIs against the existing AMR concerns and data gaps in the South African context. Based on the current evidence, we conclude that it would be reasonable to offer doxycycline PEP to high-risk MSM on a case-by-case basis, provided that it is offered by experienced sexual health clinicians in settings that have access to diagnostic STI testing and ongoing AMR surveillance.

Emergence of New Delhi metallo-beta-lactamase (NDM-1) and Klebsiella pneumoniae carbapenemase (KPC-2) in South Africa.

This report documents emergence of New Delhi metallo-beta-lactamase (NDM-1) and Klebsiella pneumoniae carbapenemase (KPC-2) in K. pneumoniae and Enterobacter cloacae in South Africa. NDM-1 producers have not been described in South Africa, and this is the first instance that KPC producers have been identified in Africa. The two patients infected with these carbapenemase-producing bacteria demised.

Does resistance in severe infections caused by methicillin-resistant Staphylococcus aureus give you the 'creeps'?

PURPOSE OF REVIEW: The clinical implications of reduced vancomycin susceptibility amongst methicillin-resistant Staphylococcus aureus (MRSA) are controversial, and crossresistance to daptomycin amongst such strains has been reported. As a consequence of 'MIC creep', higher trough levels were recommended for serious infections. This review focusses on the new data published in the past 18 months that pertain to these issues. RECENT FINDINGS: Heteroresistant vancomycin-intermediate Staphylococcus aureus reduces the clinical response rates to vancomycin in bacteraemic MRSA patients without impacting on mortality as opposed to 'MIC creep' with vancomycin minimum inhibitory concentration (MIC) levels of ≥1.5 mg/l that are significantly associated with mortality. Although daptomycin resistance is rare, 'concomitant MIC creep' amongst MRSA isolates with increasing vancomycin MICs may occur or exist concurrently amongst such strains. The aggressive vancomycin dosing regimens are still associated with unacceptable high microbiological failure rates and it is not currently possible to achieve probability of target attainment at higher vancomycin MICs of 2 mg/l. The nephrotoxic impact of high-dose vancomycin therapy has been confirmed. SUMMARY: Continued monitoring of patients on aggressive vancomycin dosing schedules is advised. Unless alternative dosing strategies prove otherwise efficacious, an alternative antibiotic should be considered for severe MRSA infections with vancomycin MICs greater than 1 mg/l. The utility of vancomycin may be waning but will depend on the prevalence of resistant MRSA phenotypes in a specific ICU.

Treating bacterial infections with bacteriophages in the 21st century.

Bacteriophages (phages) were discovered in the early part of the 20th century, and their ability to eliminate bacterial infections as bacterial viruses gathered interest almost immediately. Bacteriophage therapy was halted in the Western world due to inconclusive results in early experiments and the concurrent discovery of antibiotics. The spread of antibiotic-resistant bacteria has elicited renewed interest in bacteriophages as a natural alternative to conventional antibiotic therapy. Interest in the application of bacteriophages has also expanded to include the environment, such as wastewater treatment, agriculture and aquaculture. Although the complete phage is important in bacteriophage therapy, the focus is shifting to purified phage enzymes. These enzymes are an attractive option for pharmaceutical companies with their patent potential. They can be bio-engineered for enhanced adjuvant properties, such as a broadened spectrum of activity or binding capability. Enzymes also eliminate the concern that the prophage might integrate resistance genes into the bacterial genome. From a clinical perspective, the first randomised clinical controlled phage therapy trial was conducted with more pioneering phase I/II clinical studies on the horizon. In this opinion paper, the authors outline bacteriophages as naturally occurring bactericidal entities, their therapeutic potential against antibiotic-resistant bacteria and compare them to antibiotics. Their potential multipurpose application in the medical field is also addressed, including the use of bacteriophages for vaccination, and utilisation of the antimicrobial enzymes that they produce.

Using mystery shoppers to determine practices pertaining to antibiotic dispensing without a prescription among community pharmacies in South Africa-a pilot survey.

BACKGROUND: Inappropriate use of antimicrobials is a key factor increasing antimicrobial resistance, a major global public health problem including in South Africa. Key drivers include antibiotics being dispensed without a prescription. OBJECTIVES: To determine the accessibility of antibiotics without a prescription in community pharmacies in urban areas in South Africa and determine whether counselling was provided when antibiotics were dispensed. PATIENTS AND METHODS: Prospective, observational study, employing simulated patients (SPs), presenting with upper respiratory tract infections (URTIs) and urinary tract infections (UTIs), undertaken to establish whether antibiotics can be obtained without a valid prescription in South Africa. This pilot study was conducted in privately owned (n = 20) and corporate (franchised, n = 14) community pharmacies in three regions in Gauteng Province. RESULTS: Antibiotics were sold in privately owned pharmacies without a prescription in 80% (16/20) of cases while no antibiotics were dispensed in corporate (franchised) pharmacies. Of the 16 pharmacies selling antibiotics without a prescription, pharmacist assistants were involved in 37.5% (n = 6) and counselling was not provided to 19% of SPs. Ciprofloxacin (42.9%) and metronidazole (28.6%) were the most common antibiotics dispensed. No antibiotics were dispensed for URTIs, only UTIs. CONCLUSIONS: Dispensing antibiotics without prescriptions can be common among privately owned pharmacies in urban areas in South Africa. Corporate pharmacies, which probably have a greater income, appear to follow current legislation banning such activities. To limit selling with no prescription, community pharmacists and assistants especially in urban areas should be educated on appropriate patient care and legal requirements, with dispensing electronically monitored.

Descriptive analysis of infections due to New Delhi metallo-ß-lactamase-producing Enterobacterales in children at Red Cross War Memorial Children's Hospital.

The increased incidence and absence of antibiotic treatment options for New Delhi metallo-ß-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.

Erratum: Southern African HIV Clinicians Society 2022 guideline for the management of sexually transmitted infections: Moving towards best practice.

[This corrects the article DOI: 10.4102/sajhivmed.v23i1.1450.].

Best practices: Appropriate use of the new ß-lactam/ß-lactamase inhibitor combinations, ceftazidime-avibactam and ceftolozane-tazobactam in South Africa.

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 ß-lactam/ß-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.

Tackling antimicrobial resistance across sub-Saharan Africa: current challenges and implications for the future.

INTRODUCTION: Antimicrobial resistance (AMR) is a concern as this increases morbidity, mortality, and costs, with sub-Saharan Africa having the highest rates globally. Concerns with rising AMR have resulted in international, Pan-African, and country activities including the development of national action plans (NAPs). However, there is variable implementation across Africa with key challenges persisting. AREAS COVERED: Consequently, there is an urgent need to document current NAP activities and challenges across sub-Saharan Africa to provide future guidance. This builds on a narrative review of the literature. EXPERT OPINION: All surveyed sub-Saharan African countries have developed their NAPs; however, there is variable implementation. Countries including Botswana and Namibia are yet to officially launch their NAPs with Eswatini only recently launching its NAP. Cameroon is further ahead with its NAP than these countries; though there are concerns with implementation. South Africa appears to have made the greatest strides with implementing its NAP including regular monitoring of activities and instigation of antimicrobial stewardship programs. Key challenges remain across Africa. These include available personnel, expertise, capacity, and resources to undertake agreed NAP activities including active surveillance, lack of focal points to drive NAPs, and competing demands and priorities including among donors. These challenges are being addressed, with further co-ordinated efforts needed to reduce AMR.

Driving antibiotic stewardship awareness through the minibus-taxi community across the Tshwane District, South Africa-a baseline evaluation.

BACKGROUND: The minibus-taxi community plays an integral role within society, and for years this community has been neglected. Of late, studies on minibus-taxi operators' health and their perceptions of HIV have emerged. Antibiotic resistance is a global problem and to help curb its spread studies have looked into the knowledge, attitude and perceptions amongst students and healthcare professionals, and yet little to nothing is known about the minibus-taxi community. OBJECTIVES: To assess the knowledge and understanding of the minibus-taxi community on antibiotics and antibiotic resistance, and document indigenous antibiotic terminology used across the Tshwane District in Gauteng, South Africa. METHODS: A semi-structured questionnaire was adopted from WHO, translated into commonly spoken languages and administered to 83 minibus-taxi community members: 27 minibus-taxi operators and 56 commuters. A convenience sampling method was utilized in selecting the minibus-taxi ranks and routes. The questionnaire was later adapted to the minibus-taxi community's busy lifestyle and a section added to document antibiotic terms. RESULTS: Seventy-one percent (n = 59) of the participants knew the importance of taking antibiotics as directed, while 64% (n = 53) believed it's correct to share antibiotics. Seventy-five percent (n = 62) thought antibiotic resistance occurred in the human body. One misconception noted was that the minibus-taxi community thought antibiotics treated cold/flu and fever. Over 80% of the community were unfamiliar with antibiotic terminology. CONCLUSIONS: Several misconceptions were documented amongst the minibus-taxi community and, whilst highlighting the linguistic barriers for the term antibiotic resistance, we identified several enablers for public awareness and empowerment. Further studies are required to define appropriate indigenous terms for future educational antibiotic campaigns.

First confirmed case of infant botulism in Africa, caused by a dual-toxin-producing Clostridium botulinum strain.

Botulism, a rare life-threatening toxemia, is probably underdiagnosed in all of its forms in Africa. This study reports the first laboratory-supported case of infant botulism on the African continent. A 10-week-old, previously well infant presented with progressive global weakness, feeding difficulty, and aspiration pneumonia. During a lengthy hospitalization, a rare bivalent Clostridium botulinum strain, producing subtype B3 and F8 toxins and with a new multilocus sequence type, was isolated from stool. The infant was successfully treated with a heptavalent botulinum antitoxin infusion and pyridostigmine. Despite the relative rarity of infant botulism, this case illustrates the importance of maintaining a high level of clinical suspicion when assessing hypotonic infants. The value of modern diagnostic modalities in identifying and characterizing this under-recognized condition is also demonstrated.

South African Society of Clinical Microbiology Clostridioides difficile infection diagnosis, management and infection prevention and control guideline.

Clostridioides difficile infection (CDI) is a problem in both developed and developing countries and is a common hospital-acquired infection. This guideline provides evidence-based practical recommendations for South Africa and other developing countries. The scope of the guideline includes CDI diagnostic approaches; adult, paediatric and special populations treatment options; and surveillance and infection prevention and control recommendations.