ICU-Associated Acinetobacter baumannii Colonisation/Infection in a High HIV-Prevalence Resource-Poor Setting

BACKGROUND: There are hardly any data about the incidence, risk factors and outcomes of ICU-associated A.baumannii colonisation/infection in HIV-infected and uninfected persons from resource-poor settings like Africa. METHODS: We reviewed the case records of patients with A.baumannii colonisation/infection admitted into the adult respiratory and surgical ICUs in Cape Town, South Africa, from January 1 to December 31 2008. In contrast to colonisation, infection was defined as isolation of A.baumannii from any biological site in conjunction with a compatible clinical picture warranting treatment with antibiotics effective against A.baumannii . RESULTS: The incidence of A.baumannii colonisation/infection in 268 patients was 15 per 100 person-years, with an in-ICU mortality of 26.5 per 100 person-years. The average length of stay in ICU was 15 days (range 1-150). A.baumannii was most commonly isolated from the respiratory tract followed by the bloodstream. Independent predictors of mortality included older age (p = 0.02), low CD4 count if HIV-infected (p = 0.038), surgical intervention (p = 0.047), co-morbid Gram-negative sepsis (p = 0.01), high APACHE-II score (p = 0.001), multi-organ dysfunction syndrome (p = 0.012), and a positive blood culture for A.baumannii (p = 0.017). Of 21 A.baumannii colonised/infected HIV-positive persons those with clinical AIDS (CD4<200 cells/mm 3 ) had significantly higher in-ICU mortality and were more likely to have a positive blood culture. Conclusion In this resource-poor setting A.baumannii infection in critically ill patients is common and associated with high mortality. HIV co-infected patients with advanced immunosuppression are at higher risk of death

A retrospective descriptive analysis of non-physician-performed prehospital endotracheal intubation practices and performance in South Africa

Introduction Prehospital advanced airway management, including endotracheal intubation (ETI), is one of the most commonly performed advanced life support skills. In South Africa, prehospital ETI is performed by non-physician prehospital providers. This practice has recently come under scrutiny due to lower first pass (FPS) and overall success rates, a high incidence of adverse events (AEs), and limited evidence regarding the impact of ETI on mortality. The aim of this study was to describe non-physician ETI in a South African national sample in terms of patient demographics, indications for intubation, means of intubation and success rates. A secondary aim was to determine what factors were predictive of first pass success. Methods This study was a retrospective chart review of prehospital ETIs performed by non-physician prehospital providers, between 01 January 2017 and 31 December 2017. Two national private Emergency Medical Services (EMS) and one provincial public EMS were sampled. Data were analysed descriptively and summarised. Logistic regression was performed to evaluate factors that affect the likelihood of FPS. Results A total of 926 cases were included. The majority of cases were adults (n = 781, 84.3%) and male (n = 553, 57.6%). The most common pathologies requiring emergency treatment were head injury, including traumatic brain injury (n = 328, 35.4%), followed by cardiac arrest (n = 204, 22.0%). The mean time on scene was 46 minutes (SD = 28.3). The most cited indication for intubation was decreased level of consciousness (n = 515, 55.6%), followed by cardiac arrest (n = 242, 26.9%) and ineffective ventilation (n = 96, 10.4%). Rapid sequence intubation (RSI, n = 344, 37.2%) was the most common approach. The FPS rate was 75.3%, with an overall success rate of 95.7%. Intubation failed in 33 (3.6%) patients. The need for ventilation was inversely associated with FPS (OR = 0.42, 95% CI: 0.20–0.88, p = 0.02); while deep sedation (OR = 0.56, 95% CI: 0.36–0.88, p = 0.13) and no drugs (OR = 0.47, 95% CI: 0.25–0.90, p = 0.02) compared to RSI was less likely to result in FPS. Increased scene time (OR = 0.99, 95% CI: 0.985–0.997, p < 0.01) was inversely associated FPS. Conclusion This is one of the first and largest studies evaluating prehospital ETI in Africa. In this sample of ground-based EMS non-physician ETI, we found success rates similar to those reported in the literature. More research is needed to determine AE rates and the impact of ETI on patient outcome. There is an urgent need to standardise prehospital ETI reporting in South Africa to facilitate future research

Antimicrobial susceptibility of gram-negative pathogens isolated from patients with complicated intra-abdominal infections in South African hospitals (SMART Study 2004-2009) : impact of the new carbapenem breakpoints

BACKGROUND: The Study for Monitoring Antimicrobial Resistance Trends (SMART) follows trends in resistance among aerobic and facultative anaerobic gram-negative bacilli (GNB) isolated from complicated intra-abdominal infections (cIAIs) in patients around the world. METHODS: During 2004–2009, three centralized clinical microbiology laboratories serving 59 private hospitals in three large South African cities collected 1,218 GNB from complicated intra-abdominal infections (cIAIs) and tested them for susceptibility to 12 antibiotics according to the 2011 Clinical Laboratory Standards Institute (CLSI) guidelines. RESULTS: Enterobacteriaceae comprised 83.7% of the isolates. Escherichia coli was the species isolated most commonly (46.4%), and 7.6% of these were extended-spectrum b-lactamase (ESBL)-positive. The highest ESBL rate was documented for Klebsiella pneumoniae (41.2%). Overall, ertapenem was the antibiotic most active against susceptible species for which it has breakpoints (94.6%) followed by amikacin (91.9%), piperacillin-tazobactam (89.3%), and imipenem-cilastatin (87.1%), whereas rates of resistance to ceftriaxone, cefotaxime, ciprofloxacin, and levofloxacin were documented to be 29.7%, 28.7%, 22.5%, and 21.1%, respectively. Multi-drug resistance (MDR), defined as resistance to three or more antibiotic classes, was significantly more common in K. pneumoniae (27.9%) than in E. coli (4.9%; p < 0.0001) or Proteus mirabilis (4.1%; p < 0.05). Applying the new CLSI breakpoints for carbapenems, susceptibility to ertapenem was reduced significantly in ESBL-positive E. coli compared with ESBL-negative isolates (91% vs. 98%; p < 0.05), but this did not apply to imipenem-cilastatin (95% vs. 99%; p = 0.0928). A large disparity between imipenem-cilastatin and ertapenem susceptibility in P. mirabilis and Morganella morganii was documented (24% vs. 96% and 15% vs. 92%, respectively), as most isolates of these two species had imipenem-cilastatin minimum inhibitory concentrations in the 2–4 mcg/mL range, which is no longer regarded as susceptible. CONCLUSIONS: This study documented substantial resistance to standard antimicrobial therapy among GNB commonly isolated from cIAIs in South Africa. With the application of the new CLSI carbapenem breakpoints, discrepancies were noted between ertapenem and imipenem-cilastatin with regard to the changes in their individual susceptibilities. Longitudinal surveillance of susceptibility patterns is useful to guide recommendations for empiric antibiotic use in cIAIs.Merck & Co., Inc.http://www.liebertpub.com/overview/surgical-infections/53/am2013ay201

Starch safety in resuscitation

This correspondence is in response to the article: Parrish A, Blockman M, Starch safety in resuscitation − when will we ever learn? S Afr Med J 2013;103(6):365-367. [http://dx.doi.org/10.7196/samj.6969] in three parts:1. Starch safety in resuscitation: Withdrawal of hydroxyethyl starch solutions − a plea for evidence. R E Hodgson, G A Richards, A C Lundgren, M G L Spruyt, J P Pretorius, L R Mathiva, R Dickerson, P D Gopalan 2. Starch safety in resuscitation: Plea for evidence. M F M James, I A Joubert, J L Piercy3. Starch safety in resuscitation: Response from A Parrish and M Blockma

Large-scale genome-wide association studies and meta-analyses of longitudinal change in adult lung function.

BACKGROUND: Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function. METHODS: We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis. RESULTS: The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P  =  5.71 × 10(-7)). In addition, meta-analysis using the five cohorts with ≥3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P  =  2.18 × 10(-8)) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively. CONCLUSIONS: In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function

Protein-altering germline mutations implicate novel genes related to lung cancer development

Few germline mutations are known to affect lung cancer risk. We performed analyses of rare variants from 39,146 individuals of European ancestry and investigated gene expression levels in 7,773 samples. We find a large-effect association with an ATM L2307F (rs56009889) mutation in adenocarcinoma for discovery (adjusted Odds Ratio = 8.82, P = 1.18 × 10−15) and replication (adjusted OR = 2.93, P = 2.22 × 10−3) that is more pronounced in females (adjusted OR = 6.81 and 3.19 and for discovery and replication). We observe an excess loss of heterozygosity in lung tumors among ATM L2307F allele carriers. L2307F is more frequent (4%) among Ashkenazi Jewish populations. We also observe an association in discovery (adjusted OR = 2.61, P = 7.98 × 10−22) and replication datasets (adjusted OR = 1.55, P = 0.06) with a loss-of-function mutation, Q4X (rs150665432) of an uncharacterized gene, KIAA0930. Our findings implicate germline genetic variants in ATM with lung cancer susceptibility and suggest KIAA0930 as a novel candidate gene for lung cancer risk

Large-Scale Genome-Wide Association Studies and Meta-Analyses of Longitudinal Change in Adult Lung Function

BackgroundGenome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function.MethodsWe performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis.ResultsThe overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P  =  5.71 × 10-7). In addition, meta-analysis using the five cohorts with ≥3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P  =  2.18 × 10-8) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively.ConclusionsIn this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function