Summary Background The available data on antimicrobial stewardship programmes in Africa are scarce. The aims of this study were to assess the implementation of an antimicrobial stewardship programme ...in a setting with limited infectious disease resources. Methods We implemented a pharmacist-driven, prospective audit and feedback strategy for antimicrobial stewardship on the basis of a range of improvement science and behavioural principles across a diverse group of urban and rural private hospitals in South Africa. The study had a pre-implementation phase, during which a survey of baseline stewardship activities was done. Thereafter, a stepwise implementation phase was initiated directed towards auditing process measures to reduce consumption of antibiotics (prolonged duration, multiple antibiotics, and redundant antibiotic coverage), followed by a post-implementation phase once the model was embedded in each hospital. The effect on consumption was assessed with the WHO index of defined daily doses per 100 patient–days, and the primary outcome (change in antibiotic consumption between phases) was assessed with a linear mixed-effects regression model. Findings We implemented and assessed the antimicrobial stewardship programme between Oct 1, 2009, and Sept 30, 2014. 116 662 patients receiving antibiotics at 47 hospitals during 104 weeks of standardised measurement and feedback, were reviewed, with 7934 interventions by pharmacists recorded for the five targeted measures, suggesting that almost one in 15 prescriptions required intervention. 3116 (39%) of 7934 pharmacist interventions were of an excessive duration. The antimicrobial stewardship programme led to a reduction in mean antibiotic defined daily doses per 100 patient–days from 101·38 (95% CI 93·05–109·72) in the pre-implementation phase to 83·04 (74·87–91·22) in the post-implementation phase (p<0·0001). Interpretation Health-care facilities with limited infectious diseases expertise can achieve substantial returns through pharmacist-led antimicrobial stewardship programmes and by focusing on basic interventions. Funding None.
A series of colistin-resistant Escherichia coli clinical isolates was recovered from hospitalized and community patients in South Africa. Seven clonally unrelated isolates harbored the mcr-1 gene ...located on different plasmid backbones. Two distinct plasmids were fully sequenced, and identical 2,600-bp-long DNA sequences defining a mcr-1 cassette were identified. Promoter sequences responsible for the expression of mcr-1, deduced from the precise identification of the +1 transcription start site for mcr-1, were characterized.
Summary In February, 2016, WHO released a report for the development of national action plans to address the threat of antibiotic resistance, the catastrophic consequences of inaction, and the need ...for antibiotic stewardship. Antibiotic stewardship combined with infection prevention comprises a collaborative, multidisciplinary approach to optimise use of antibiotics. Efforts to mitigate overuse will be unsustainable without learning and coordinating activities globally. In this Personal View, we provide examples of international collaborations to address optimal prescribing, focusing on five countries that have developed different approaches to antibiotic stewardship—the USA, South Africa, Colombia, Australia, and the UK. Although each country's approach differed, when nurtured, individual efforts can positively affect local and national antimicrobial stewardship programmes. Government advocacy, national guidelines, collaborative research, online training programmes, mentoring programmes, and social media in stewardship all played a role. Personal relationships and willingness to learn from each other's successes and failures continues to foster collaboration. We recommend that antibiotic stewardship models need to evolve from infection specialist-based teams to develop and use cadres of health-care professionals, including pharmacists, nurses, and community health workers, to meet the needs of the global population. We also recommend that all health-care providers who prescribe antibiotics take ownership and understand the societal burden of suboptimal antibiotic use, providing examples of how countries can learn, act globally, and share best antibiotic stewardship practices.
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.
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.
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.
Few data exist on the implementation of process measures to facilitate adherence to peri-operative antibiotic prophylaxis (PAP) guidelines in Africa.
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.
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.
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).
The implementation of process improvement initiatives and principles targeted to institutional needs utilizing pharmacists can effectively improve PAP guideline compliance and sustainable patient outcomes.
Given the complexity and resources required to determine paediatric age-specific and indication-specific antibiotic use, dosing, and duration determinants, and other outpatient prescribing quality ...indicators, without universal national electronic health records, in our opinion Hsia and colleagues have provided a comprehensible picture of the general trends of global community childhood antibiotic prescribing across different countries. Despite many limitations, including measuring sales volume reported in standard units rather than conventional population-based standardisation consumption, these three metrics together might serve as a simple index or measure of antibiotic selection pressure for resistance at the community level. The first laudable attempt to develop simple metrics of global child community antibiotic use, based on the WHO AWaRe classification, is a necessity that was until now a challenge in most lower-income and middle-income countries.7 We declare no competing interests.
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.
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.
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.
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.
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.
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.
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.
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