Utility of the BioFire® FilmArray® Pneumonia Panel plus assay for syndromic testing of lower respiratory tract infections in a low/middle-income setting.

Background: Determining lower respiratory tract infection (LRTI) aetiology is complex. Culture-based methods are laborious with poor sensitivity. Molecular assays improve detection of potential pathogens, but incorrect interpretation of results may lead to inappropriate antimicrobial therapy. Methods: The utility of the BioFire® FilmArray® Pneumonia Panel plus (FA-PP) to detect LRTI pathogens, and the potential impact on antimicrobial stewardship in a low-resource setting, were assessed. Routine LRT samples were included from adult patients with clinically suspected LRTI or with a concomitant blood culture at Groote Schuur Hospital and referring facilities. Culture and FA-PP results were compared, and pharmacy data analysed to determine appropriateness of antibiotic therapy. Results: There was an 80% correlation between cultured LRTI pathogens and the FA-PP bin ≥107 results. Compared with culture, the FA-PP detected substantially more pathogens (86.6% versus 17.9%) and produced a combined 100% positive percent agreement, and 88% negative percent agreement. The FA-PP detected bacterial/viral coinfections in 27% of samples. Correlation of FA-PP results with pharmacy data (n = 69) indicated a potential antibiotic change in 75% of cases, but this is difficult to accurately characterize without a 'gold standard' for treatment or complete clinical data. Conclusions: The FA-PP increased the number of positive samples with typical bacteria, but the semi-quantitative reporting algorithm does not describe the correlation between the different bin values and colonization versus infection. This complicates result interpretation and may lead to inappropriate antimicrobial treatment. This study highlights the potential positive impact of rapid molecular assays for routine care in lower-income settings, but also underscores the interpretive challenges associated with these tests.

Hydatid brain cyst: A delayed diagnosis in a rural setting during COVID-19.

A previously healthy 10-year-old girl, living in a sheep-farming community in South Africa with exposure to dogs, presented to her local hospital with generalised tonic-clonic seizures. The initial clinical assessment and laboratory work-up were unremarkable. When she presented with further seizures 6 months later, attempts to arrange neuroimaging and specialist assessment were unsuccessful owing to restrictions on routine healthcare services during the SARS-CoV-2 nationwide lockdown. Subsequently, 11 months after her first presentation, she developed focal neurological signs suggestive of raised intracranial pressure. A brain computed tomography scan revealed a left-sided cerebral cyst and imminent tonsillar herniation. An emergency burr-hole procedure was performed to relieve the raised intracranial pressure, followed by definitive neurosurgical excision of cysts. Hydatid protoscolices and hooklets were seen on microscopy of cyst fluid, and treatment with albendazole and praziquantel was initiated. While her infection was treated successfully, long-term sequelae including permanent blindness and hemiparesis could potentially have been prevented with early neuroimaging and surgical intervention.

Using ceftazidime-avibactam for persistent carbapenem-resistant Serratia marcescens infection highlights antimicrobial stewardship challenges with new beta-lactam-inhibitor combination antibiotics.

The newer beta-lactam-inhibitor combination (BLIC) antibiotics are available in South Africa (SA) for the treatment of carbapenem-resistant Enterobacterales infections. We describe the successful use of ceftazidime-avibactam (CA) for the treatment of a child with persistent carbapenem-resistant Serratia marcescens bacteraemia, and the challenges faced using this lifesaving antibiotic, including access to susceptibility testing, procurement process, cost and complexity of deciding when, how and for how long to use it. Furthermore, the burden of carbapenem resistance is increasing in SA, and inappropriate use of CA and other newer BLIC antibiotics, such as ceftolozane-tazobactam, will inevitably endanger their longevity. A careful balance must be struck between removing unnecessary obstacles and delays in initiating these antibiotics for life-threatening infections, and additional antimicrobial stewardship-guided interventions aimed at preserving their therapeutic use.

Implementing a multi-faceted framework for proprietorship of hand hygiene compliance in a network of South African hospitals: leveraging the Ubuntu philosophy.

BACKGROUND: Given the lack of hospital-wide ownership and shortage of nurses, the ideal model for large-scale implementation of hand hygiene (HH) behaviour change in low- and middle-income countries is unknown. AIM: The aim of the multi-modal strategy was to engender hospital accountability for HH compliance. METHODS: The quasi-experimental study was conducted in 50 South African hospitals (November 2015 to July 2017) and involved five overlapping phases: executive governance and corporate behaviour change; group-wide systematic situational analysis; development of an electronic-assisted direct-observed data collection and analysis application; launch and implementation; and accountable governance. Measurement of intra- and inter-hospital variance to six HH opportunities was calculated and data compliance dashboards were e-mailed weekly to hospital leadership teams to provide feedback of recorded HH compliance and behaviour to frontline teams. Baseline comparison (July 2016) of compliance was compared versus post-implementation (July 2017). FINDINGS: Baseline HH compliance of ≤60% was documented for 16% (8/50) of hospitals, whereas overall, 48% (24/50) of hospitals demonstrated a significant improvement (P < 0.01). Over the 13-month observation period, 523,422 observations were recorded with a mean rate of 277 ± 223 observations per 1000 patient-days. The group mean composite compliance improved by 7.8% (P < 0.01) from 77.4% ± 12.8 to 85.2% ± 8.8 between July 2016 and July 2017, respectively. CONCLUSION: Implementation of a multi-faceted HH model in a large, diverse group of South African hospitals translated into changes in the organizational systems and accountability, standardized HH compliance management and feedback that led to HH proprietorship.

Rational use of the fluoroquinolones.

The systemic fluoroquinolones (FQs) have recently been reported to be associated with significant side-effects in susceptible individuals. This has prompted the Food and Drug Administration (FDA) in the USA and the European Medicines Agency (EMA) to issue warnings regarding their use. The FQs should not be used for common bacterial infections, such as urinary tract infections, travellers' diarrhoea and upper and lower respiratory tract infections, unless it is not possible to use another oral agent. There are situations, however, in which these agents are not only effective, but their benefit outweighs the risk. These include the management of conditions such as acute prostatitis, typhoid fever, prosthetic joint infections, multidrug-resistant tuberculosis, certain hospital-acquired infections and situations where the organism is susceptible to FQs, which could then be administered orally. Alternatively, the patient would have to be admitted to hospital for parenteral therapy.

Opportunities to optimise colistin stewardship in hospitalised patients in South Africa: Results of a multisite utilisation audit

Background. Colistin is an old antibiotic that has been reintroduced as salvage therapy in hospitalised patients because it is frequently the only agent active against Gram-negative bacteria. Various guidelines for colistin administration have led to confusion in establishing the appropriate dose, which has potential for adverse consequences including treatment failure or toxicity. The emergence and spread of colistin resistance has been documented in South Africa (SA), but no local information exists on how and why colistin is used in hospitals, and similarly, compliance with current dosing guidelines is unknown.Objectives. To evaluate the current utilisation of colistin in SA hospitals, in order to identify stewardship opportunities that could enhance the appropriate use of this antibiotic.Methods. Electronic patient records of adult patients on intravenous (IV) colistin therapy for >72 hours in four private hospitals were retrospectively audited over a 10-month period (1 September 2015 - 30 June 2016). The following data were recorded: patient demographics, culture and susceptibility profiles, diagnosis, and indication for use. Compliance with six colistin process measures was audited: obtaining a culture prior to initiation, administration of a loading dose, administration of the correct loading dose, adjustments to maintenance dose according to renal function, whether colistin was administered in combination with another antibiotic, and whether de-escalation following culture and sensitivity results occurred. Outcome measures included effects on renal function, overall hospital mortality, intensive care unit length of stay (LoS), and hospital LoS.Results. Records of 199 patients on IV colistin were reviewed. There was 99.0% compliance with obtaining a culture prior to antibiotic therapy, 93.5% compliance with prescription of a loading dose, and 98.5% compliance regarding prescription of colistin in combination with another agent. However, overall composite compliance with the six colistin stewardship process measures was 82.0%. Non-compliance related to inappropriate loading and maintenance doses, lack of adjustment according to renal function and lack of de-escalation following culture sensitivity was evident. Significantly shorter durations of treatment were noted in patients who received higher loading doses (p=0.040) and in those who received maintenance doses of 4.5 MU twice daily v. 3 MU three times daily (p=0.0027). In addition, compared with patients who survived, more patients who died received the 3 MU three times daily maintenance dose (p=0.0037; phi coefficient 0.26).Conclusions. The study identified multiple stewardship opportunities to optimise colistin therapy in hospitalised patients. Urgent implementation of a stewardship bundle to improve colistin utilisation is warranted

Opportunities to optimise colistin stewardship in hospitalised patients in South Africa: Results of a multisite utilisation audit.

BACKGROUND: Colistin is an old antibiotic that has been reintroduced as salvage therapy in hospitalised patients because it is frequently the only agent active against Gram-negative bacteria. Various guidelines for colistin administration have led to confusion in establishing the appropriate dose, which has potential for adverse consequences including treatment failure or toxicity. The emergence and spread of colistin resistance has been documented in South Africa (SA), but no local information exists on how and why colistin is used in hospitals, and similarly, compliance with current dosing guidelines is unknown. OBJECTIVES: To evaluate the current utilisation of colistin in SA hospitals, in order to identify stewardship opportunities that could enhance the appropriate use of this antibiotic. METHODS:  Electronic patient records of adult patients on intravenous (IV) colistin therapy for >72 hours in four private hospitals were retrospectively audited over a 10-month period (1 September 2015 - 30 June 2016). The following data were recorded: patient demographics, culture and susceptibility profiles, diagnosis, and indication for use. Compliance with six colistin process measures was audited: obtaining a culture prior to initiation, administration of a loading dose, administration of the correct loading dose, adjustments to maintenance dose according to renal function, whether colistin was administered in combination with another antibiotic, and whether de-escalation following culture and sensitivity results occurred. Outcome measures included effects on renal function, overall hospital mortality, intensive care unit length of stay (LoS), and hospital LoS. RESULTS: Records of 199 patients on IV colistin were reviewed. There was 99.0% compliance with obtaining a culture prior to antibiotic therapy, 93.5% compliance with prescription of a loading dose, and 98.5% compliance regarding prescription of colistin in combination with another agent. However, overall composite compliance with the six colistin stewardship process measures was 82.0%. Non-compliance related to inappropriate loading and maintenance doses, lack of adjustment according to renal function and lack of de-escalation following culture sensitivity was evident. Significantly shorter durations of treatment were noted in patients who received higher loading doses (p=0.040) and in those who received maintenance doses of 4.5 MU twice daily v. 3 MU three times daily (p=0.0027). In addition, compared with patients who survived, more patients who died received the 3 MU three times daily maintenance dose (p=0.0037; phi coefficient 0.26). CONCLUSIONS:  The study identified multiple stewardship opportunities to optimise colistin therapy in hospitalised patients. Urgent implementation of a stewardship bundle to improve colistin utilisation is warranted.

Erratum to: Antimicrobials: a global alliance for optimizing their rational use in intra-abdominal infections (AGORA).

[This corrects the article DOI: 10.1186/s13017-016-0089-y.].

Stepwise introduction of the 'Best Care Always' central-line-associated bloodstream infection prevention bundle in a network of South African hospitals.

BACKGROUND: Healthcare-associated infection (HCAI) remains a major international problem. AIM: The 'Best Care Always!' (BCA) campaign was launched in South Africa to reduce preventable HCAI, including central-line-associated bloodstream infection (CLABSI). METHODS: The intervention took place in 43 Netcare Private Hospitals, increasing later to 49 with 958 intensive care units (ICUs) and 439 high-care (HC) beds and 1207 ICUs and 493 HC beds, respectively. Phase 1, April 2010 to March 2011, ICU infection prevention and control (IPC) nurse-driven change: commitment from management and doctors and training of IPC nurses. Bundle compliance and infections per 1000 central-line-days were incorporated as standard IPC measures and captured monthly. Phase 2, April 2011 to March 2012, breakthrough collaborative method: multiple regional learning sessions for nursing leaders, IPC nurses and unit managers. Phase 3, April 2012 to May 2016: sustained goal-setting, benchmarks, ongoing audits. FINDINGS: A total of 1,119,558 central-line-days were recorded. Bundle compliance improved significantly from a mean of 73.1% [standard deviation (SD): 11.2; range: 40.6-81.7%] in Phase 1 to a mean of 90.5% (SD: 4.7; range: 76.5-97.2%) in Phase 3 (P = 0.0004). The CLABSI rate declined significantly from a mean of 3.55 (SD: 0.82; range: 2.54-5.78) per 1000 central-line-days in Phase 1 to a mean of 0.13 (SD: 0.09; range: 0-0.33) (P < 0.0001). CONCLUSION: This intervention, the first of its kind in South Africa, through considerable motivation and education, and through competition between hospitals resulted in significant decreases in CLABSI.

Albumin concentration significantly impacts on free teicoplanin plasma concentrations in non-critically ill patients with chronic bone sepsis.

The impact of decreased serum albumin concentrations on free antibiotic concentrations in non-critically ill patients is poorly described. This study aimed to describe the pharmacokinetics of a high-dose regimen of teicoplanin, a highly protein-bound antibiotic, in non-critically ill patients with hypoalbuminaemia. Ten patients with chronic bone sepsis and decreased serum albumin concentrations (<35 g/L) receiving teicoplanin 12 mg/kg 12-hourly intravenously for 48 h followed by 12 mg/kg once daily were enrolled. Surgical debridement was performed on Day 3. Samples of venous blood were collected pre-infusion and post-infusion during the first 4 days of therapy. Total and free teicoplanin concentrations were assayed using validated chromatographic methods. The median serum albumin concentration for the cohort was 18 (IQR 15-24) g/L. After 48 h, the median (IQR) free trough (fC(min)) and total trough (tC(min)) concentrations were 2.90 (2.67-3.47) mg/L and 15.54 (10.28-19.12) mg/L, respectively, although trough concentrations declined thereafter. Clearance of the free concentrations was significantly high relative to the total fraction at 38.6 (IQR 29.9-47.8) L/h and 7.0 (IQR 6.8-9.8) L/h, respectively (P<0.001). Multiple linear regression analysis demonstrated that whereas total teicoplanin concentration did not impact on free concentrations (P=0.174), albumin concentration did (P<0.001). This study confirms the significant impact of hypoalbuminaemia on free concentrations of teicoplanin in non-critically ill patients, similar to that in critically ill patients. Furthermore, the poor correlation with total teicoplanin concentration suggests that therapeutic drug monitoring of free concentrations should be used in these patients.

Guideline summary: appropriate use of tigecycline.

Tigecycline, the first of a new class of broad-spectrum antibiotics (the glycylcyclines), has been licensed in South Africa for the parenteral treatment of adult patients with complicated intra-abdominal infections (cIAIs) and complicated skin and soft-tissue infections (cSSTIs). This article serves as a summary of the guideline on the appropriate use of tigecycline, published in mid-2010 as a collaborative effort by representatives of the Association of Surgeons of South Africa, the Critical Care Society of Southern Africa, the Federation of Infectious Diseases Societies of Southern Africa, the South African Thoracic Society and the Trauma Society of South Africa.

Guideline: appropriate use of tigecycline.

INTRODUCTION: Tigecycline, the first of a new class of antibiotics, the glycylcyclines, was licensed in South Africa for the parenteral treatment of adult patients with complicated intra-abdominal infections (cIAIs) and complicated skin and soft-tissue infections (cSSTIs). METHODS: A multidisciplinary meeting representative of the Association of Surgeons of South Africa, the Critical Care Society of Southern Africa, the Federation of Infectious Diseases Societies of Southern Africa, the South African Thoracic Society and the Trauma Society of South Africa was held to draw up a national guideline for the appropriate use of tigecycline. Background information reviewed included randomised controlled trials, other relevant publications and local antibiotic susceptibility patterns. The initial document was drafted at the meeting. Subsequent drafts were circulated to members of the working group for modification. OUTPUT: The guideline addresses several important aspects of the new agent, summarising key clinical data and highlighting important considerations with the use of the drug. The recommendations in this guideline are based on currently available scientific evidence together with the consensus opinion of the authors. CONCLUSION: This statement was written out of concern regarding the widespread misuse of antibiotics. Its primary intention is to facilitate heterogeneous use of antibiotics as a component of antibiotic stewardship and to highlight the appropriate use of tigecycline in particular.

Strategies for heart disease in sub-Saharan Africa.

The commonest forms of heart disease in sub-Saharan Africa are chronic rheumatic heart disease, dilated cardiomyopathy, pulmonary heart disease, infectious forms of heart disease including chronic, constrictive and infective endocarditis, genetic forms of heart disease and arrhythmias. Malnutrition, with cardiac manifestations such as beriberi, and alcoholism also play a part. Ischaemic heart disease in sub-Saharan Africa at present affects mainly the small, Westernised white population. Heart disease is a less important cause of morbidity and mortality than many other infectious diseases but is likely to escalate in the next generation(s). The changing demographic picture dictates the way in which funds for research, prevention and treatment must be channelled to best advantage. A concerted effort must be made by cardiologists of African countries to arrest the advance of heart disease, and a declaration outlining these strategies has been endorsed by the Pan-African Society of Cardiology (PASCAR).

Pharmacokinetics of once-daily dosing of ertapenem in critically ill patients with severe sepsis.

Adequate data on the pharmacokinetics of once-daily administration of ertapenem in critically ill patients are largely lacking. This single-centre, prospective, open-label study was performed on a cohort of eight critically ill patients with severe sepsis with normal renal function treated with 1g of ertapenem once daily. Samples of venous blood and urine were collected before infusion and at specific time points in the 24-h post-infusion period. Plasma and urine ertapenem levels were determined by reverse-phase high-performance liquid chromatography (HPLC) with ultraviolet detection. The non-protein-bound fraction was determined in the filtrate by HPLC using a Centrifree device. The current study showed a lower maximum plasma concentration (C(max)) (52.3.0mg/L vs. 253 mg/L) and area under the concentration-time curve from 0 h to infinity (AUC(0-infinity)) (188 mg h/L vs. 817 mg h/L) but higher volume of distribution at steady state (V(ss)) (26.8L vs. 5.7 L) compared with those observed in young healthy volunteers. For unbound ertapenem, geometric means of C(max) and AUC(0-infinity) were 29.5mg/L and 103.5 mg h/L, respectively, and correlated negatively with hypoalbuminaemia. Unbound levels failed to exceed a minimum inhibitory concentration of 1mg/L for more than 7.1h (30%) of the dosing interval in two patients. The highly variable and unpredictable intersubject pharmacokinetic parameters documented in this study resulted in suboptimal unbound concentrations in some patients. This raises the question as to whether ertapenem is an appropriate agent for initial use in critically ill patients with severe sepsis.

Recommendations to achieve rapid therapeutic teicoplanin plasma concentrations in adult hospitalised patients treated for sepsis.

The optimum teicoplanin loading dose and duration of therapy required for rapid attainment of a therapeutic trough plasma concentration (C(min)) (> or = 10mg/L for serious Gram-positive infections and > or = 20mg/L for deep-seated infections) are not known. In this open-label, multicentre, observational study, teicoplanin levels were determined following administration of loading doses of 6 mg/kg every 12h on Day 1 followed by 6 mg/kg once or twice daily to hospitalised patients with suspected or diagnosed Gram-positive infections. C(min) levels for the first 4 days of treatment were collected 15min prior to drug administration. Levels were determined with an Abbott TDx/FLx Analyzer and Seradyn Teicoplanin Innofluor Assay Kit. The two target trough values (> or = 10mg/L and > or = 20mg/L) were only achieved by Day 4 in the once-daily group (n=34; mean 9.55 mg/L, 95% confidence interval (CI) 8.17-10.94 mg/L) and in the twice-daily group (n=40; mean 21.8 mg/L, 95% CI 17.21-26.39 mg/L), respectively. However, the mean C(min) in the twice-daily group was > or = 10mg/L (11.03 mg/L) by Day 2. To achieve rapid therapeutic C(min) concentrations targeted for the majority of serious Gram-positive infections, we recommend teicoplanin loading doses of 6 mg/kg every 12h for 48h followed by once-daily for infections other than infective endocarditis, septic arthritis and osteomyelitis. Regarding the latter infections, higher loading doses might be warranted to reach rapid steady-state concentrations.