Antimicrobial Stewardship: Leveraging the "Butterfly Effect" of Hand Hygiene.

It is vital that there are coordinated, collaborative efforts to address the threat of antimicrobial resistance (AMR) and to prevent and control the spread of hospital-onset infections, particularly those due to multidrug-resistant (MDR) pathogens. The butterfly effect is a concept in which metaphorically speaking, small, seemingly trivial events ultimately cascade into something of far greater consequence, more specifically by having a non-linear impact on very complex systems. In this regard, antimicrobial stewardship programs (ASP), when implemented alongside infection prevention control (IPC) interventions in hospitals, particularly hand hygiene (HH), are significantly more effective in reducing the development and spread of AMR bacteria than implementation of ASP alone. In this perspective, we briefly review the evidence for the combined effect, and call for closer collaboration between institutional IPC and ASP leadership, and for well-functioning IPC programs to ensure the effectiveness of ASP.

Microbiology Assessments in Critically Ill Patients.

The prevalence of suspected or proven infections in critically ill patients is high, with a substantial attributable risk to in-hospital mortality. Coordinated guidance and interventions to improve the appropriate microbiological assessment for diagnostic and therapeutic decisions are therefore pivotal. Conventional microbiology follows the paradigm of "best practice" of specimen selection and collection, governed by laboratory processing and standard operating procedures, and informed by the latest developments and trends. In this regard, the preanalytical phase of a microbiological diagnosis is crucial since inadequate sampling may result in the incorrect diagnosis and inappropriate management. In addition, the isolation and detection of contaminants interfere with multiple intensive care unit (ICU) processes, which confound the therapeutic approach to critically ill patients. To facilitate bedside enablement, the microbiology laboratory should provide expedited feedback, reporting, and interpretation of results. Compared with conventional microbiology, novel rapid and panel-based diagnostic strategies have the clear advantages of a rapid turnaround time, the detection of many microorganisms including antimicrobial resistant determinants and thus promise substantial improvements in health care. However, robust data on the clinical evaluation of rapid diagnostic tests in presumed sepsis, sepsis and shock are extremely limited and more rigorous intervention studies, focusing on direct benefits for critically ill patients, are pivotal before widespread adoption of their use through the continuum of ICU stay. Advocating the use of these diagnostics without firmly establishing which patients would benefit most, how to interpret the results, and how to treat according to the results obtained, could in fact be counterproductive with regards to diagnostic "best practice" and antimicrobial stewardship. Thus, for the present, they may supplement but not yet supplant conventional microbiological assessments.

Clinical management of severe infections caused by carbapenem-resistant gram-negative bacteria: a worldwide cross-sectional survey addressing the use of antibiotic combinations.

OBJECTIVES: Optimal treatment of carbapenem-resistant Gram-negative bacteria (CR-GNB) infections is uncertain because of the lack of good-quality evidence and the limited effectiveness of available antibiotics. The aim of this survey was to investigate clinicians' prescribing strategies for treating CR-GNB infections worldwide. METHODS: A 36-item questionnaire was developed addressing the following aspects of antibiotic prescribing: respondent's background, diagnostic and therapeutic availability, preferred antibiotic strategies and rationale for selecting combination therapy. Prescribers were recruited following the snowball sampling approach, and a post-stratification correction with inverse proportional weights was used to adjust the sample's representativeness. RESULTS: A total of 1012 respondents from 95 countries participated in the survey. Overall, 298 (30%) of the respondents had local guidelines for treating CR-GNB at their facility and 702 (71%) had access to Infectious Diseases consultation, with significant discrepancies according to country economic status: 85% (390/502) in high-income countries versus 59% (194/283) in upper-medium-income countries and 30% (118/196) in lower-middle-income countries/lower-income-countries). Targeted regimens varied widely, ranging from 40 regimens for CR-Acinetobacter spp. to more than 100 regimens for CR-Enterobacteriaceae. Although the majority of respondents acknowledged the lack of evidence behind this choice, dual combination was the preferred treatment scheme and carbapenem-polymyxin was the most prescribed regimen, irrespective of pathogen and infection source. Respondents noticeably disagreed around the meaning of 'combination therapy' with 20% (150/783) indicating the simple addition of multiple compounds, 42% (321/783) requiring the presence of in vitro activity and 38% (290/783) requiring in vitro synergism. CONCLUSIONS: Management of CR-GNB infections is far from being standardized. Strategic public health focused randomized controlled trials are urgently required to inform evidence-based treatment guidelines.

Best practice: antibiotic decision-making in ICUs.

PURPOSE OF REVIEW: A major challenge in the ICU is optimization of antibiotic use. This review assesses current understanding of core best practices supporting and promoting astute antibiotic decision-making. RECENT FINDINGS: Limiting exposure to the shortest effective duration is the cornerstone of antibiotic decision-making. The decision to initiate antibiotics should include assessment of risk for resistance. This requires synthesis of patient-level data and environmental factors to determine whether delayed initiation could be considered in some patients with suspected sepsis until sensitivity data is available. Until improved stratification scores and clinically meaningful cut-off values to identify MDR are available and externally validated, decisions as to which empiric antibiotic is used should rely on syndromic antibiograms and institutional guidance. Optimization of initial and maintenance doses is another enabler of enhanced outcome. Stewardship practices must be streamlined by re-assessment to minimize negative effects, such as a potential increase in duration of therapy and increased risk of collateral damage from exposure to multiple, sequential antibiotics that may ensue from de-escalation. SUMMARY: Multiple challenges and research priorities for antibiotic optimization remain; however, the best stewardship practices should be identified and entrenched in daily practice. Reducing unnecessary exposure remains a vital strategy to limit resistance development.

The role of appropriate diagnostic testing in acute respiratory tract infections: An antibiotic stewardship strategy to minimise diagnostic uncertainty in primary care.

Antibiotic resistance has increased worldwide to the extent that it is now regarded as a global public health crisis. Interventions to reduce excessive antibiotic prescribing to patients can reduce resistance and improve microbiological and clinical outcomes. Therefore, although improving outpatient antibiotic use is crucial, few data are provided on the key interventional components and the effectiveness of antibiotic stewardship in the primary care setting, in South Africa. The reasons driving the excessive prescription of antibiotics in the community are multifactorial but, perhaps most importantly, the overlapping clinical features of viral and bacterial infections dramatically reduce the ability of GPs to distinguish which patients would benefit from an antibiotic or not. As a consequence, the need for tools to reduce diagnostic uncertainty is critical. In this regard, besides clinical algorithms, a consensus of collaborators in European and UK consortia recently provided guidance for the use of C-reactive protein point-of-care testing in outpatients presenting with acute respiratory tract infections (ARTIs) and/or acute cough, if it is not clear after proper clinical assessment whether antibiotics should be prescribed or not. A targeted application of stewardship principles, including diagnostic stewardship as described in this review, to the ambulatory setting has the potential to affect the most common indications for systemic antibiotic use, in that the majority (80%) of antibiotic use occurs in the community, with ARTIs the most common indication.

Emergence of plasmid-mediated colistin resistance (MCR-1) among Escherichia coli isolated from South African patients.

The polymyxin antibiotic colistin is an antibiotic of last resort for the treatment of extensively drug-resistant Gram-negative bacteria, including carbapenemase-producing Enterobacteriaceae. The State of the World's Antibiotics report in 2015 highlighted South Africa (SA)'s increasing incidence of these 'superbugs' (3.2% of Klebsiella pneumoniae reported from SA were carbapenemase producers), and in doing so, underscored SA's increasing reliance on colistin as a last line of defence. Colistin resistance effectively renders such increasingly common infections untreatable.

Updated recommendations for the management of upper respiratory tract infections in South Africa.

BACKGROUND: Inappropriate use of antibiotics for non-severe upper respiratory tract infections (URTIs), most of which are viral, significantly adds to the burden of antibiotic resistance. Since the introduction of pneumococcal conjugate vaccines in 2009 in South Africa, the relative frequency of the major bacterial pathogens causing acute otitis media (AOM) and acute bacterial rhinosinusitis (ABRS) has changed. RECOMMENDATIONS: Since URTIs are mostly viral in aetiology and bacterial AOM and ABRS frequently resolve spontaneously, the guideline includes diagnostic criteria to separate viral from bacterial causes and hence, those patients not requiring antibiotics. Penicillin remains the drug of choice for tonsillopharyngitis. Amoxicillin remains the drug of choice for both AOM and ABRS. A dose of 90 mg/kg/day is recommended for children, which should be effective for pneumococci with high-level penicillin resistance and will also cover most infections with H. influenzae. Amoxicillin-clavulanate (in high-dose amoxicillin formulations available for both children and adults) should be considered initial treatment of choice in patients with recent antibiotic therapy with amoxicillin (previous 30 days) and with resistant H.influenzae infections pending the results of studies of local epidemiology (ß-lactamase production ≥15%). The macrolide/azalide class of antibiotics are not recommended routinely for URTIs and are reserved for ß-lactam allergic patients. CONCLUSION: The guideline should facilitate rational antibiotic prescribing for URTIs as a component of antibiotic stewardship. However, it requires updating when new information becomes available particularly from randomised controlled trials and surveillance studies of local etiology and antibiotic susceptibility patterns.