A standardised approach to the treatment and management of significant acinetobacter species infection at academic complex hospitals in KwaZulu-Natal.

Doctoral Degree. University of KwaZulu-Natal, Durban.Introduction: Carbapenem-resistant Acinetobacter species (Acinetobacter spp.) are increasingly recognised as important pathogens, whose resistance patterns present a high-risk global challenge. However, there is limited scientific data and a lack of a standardised approach to help the clinician select optimal therapy in local setting. This study aimed to provide a standardised approach for the management of significant Acinetobacter spp. infection based on phenotypic and genotypic characterisation of local isolates, as well as clinical characteristics and outcomes of patients at academic complex hospitals in KwaZulu-Natal. Objectives: The significance of Acinetobacter spp. infections and the most effective drug combinations for optimal therapy were determined. Acinetobacter spp. isolates were phenotypically and genotypically characterised. This was followed by the development of a standard management guideline for local use, based on the data obtained in the different objectives. Methods: The research consisted of a retrospective and prospective observational and experimental laboratory component. The laboratory component included synergy testing of colistin, susceptibility to antimicrobial agents in use at local hospitals, polymerase chain reaction and sequencing for analysis of the resistant genes related to carbapenem, colistin and amikacin. Phenotypic, genotypic, and clinical characterisation were utilised to develop a standardised management approach of significant Acinetobacter spp. infection. Results: Acinetobacter spp. was identified as a significant cause of sepsis and mortality among patients in a surgical intensive care unit (ICU). Cases of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Acinetobacter spp. increased over seven years, together with the emergence of pandrug-resistant (PDR) isolates. The results of synergy testing of colistin combinations with amikacin, carbapemens (imipemen, meropenem), ciprofloxacin, tazocin, linezolid, rifampicin and vancomycin against Acinetobacter spp. was highly diverse and speciesdependent. Characterisation of Acinetobacter spp. isolates showed that oxacillinase β-lactamase (OXA-23)-producing MDR isolates correlated with their antibiogram. Pulsed field gel electrophoresis (PFGE) showed horizontal transfer between seven clusters, each containing two patients each, totalling 14 patients. However, the PFGE typing revealed a diverse collection of MDR Acinetobacter spp. clones, and that isolates from not more than two patients were related. This suggests, therefore, that no outbreak had occurred based on the PFGE typing interpretation. Further genetic investigation revealed that the aphA6 gene were associated with amikacin resistance and IpxA gene may be associated with colistin resistance in our local setting. Conclusion: The results highlighted the importance of antibiotic stewardship in the treatment of Acinetobacter spp. infection. Individual-specific antibiograms are recommended as the best 2 approach for treatment in KwaZulu-Natal (KZN) and synergy testing should be performed for individualised direct therapy. The clinical and microbiological indicators of significant infection are crucial when establishing the decision to treat. The study provided a valuable standardised approach, including a flow chart of criteria for sepsis and colonisation; a standardised algorithm for the management; and synergy test at academic complex hospitals, Medical Microbiology laboratory, National Health Laboratory Service (NHLS) in KZN

Antimicrobial susceptibility patterns of uropathogens isolated from pregnant women in KwaZulu-Natal Province: 2011 - 2016

Background. Urinary tract infection (UTI) is one of the most common infections during pregnancy, which can lead to significant maternal and perinatal morbidity and mortality if left untreated. Challenges when treating UTIs in pregnancy include fetal protection and resistance development of uropathogens. Currently, the Essential Medicines List recommends nitrofurantoin to treat cystitis and ceftriaxone to treat pyelonephritis in pregnant women.Objectives. To determine common pathogens causing UTI in pregnancy and their antibiotic susceptibility patterns.Methods. A retrospective analysis was performed of laboratory data for positive urine specimens from obstetric departments of 6 KwaZulu- Natal Province hospitals during 2011 - 2016. Identification and susceptibility testing were performed using the VITEK 2 system. Results were interpreted according to the breakpoints of the Clinical and Laboratory Standards Institute, USA.Results. From 5 971 positive urine specimens, the most common isolate was Escherichia coli (n=3 236; 54.2%), followed by Klebsiella pneumoniae (n=770; 12.9%). Group B streptococcus (GBS) (n=239; 4.0%) and Enterococcus faecalis (n=251; 4.2%) were the most common Gram-positive pathogens. E. coli displayed significant resistance to trimethoprim-sulfamethoxazole (65.1%), cephalothin (38.3%), cefuroxime (27.3%), ciprofloxacin (16.9%) and amoxicillin-clavulanic acid (17.1%). Resistance to ceftriaxone and nitrofurantoin remained low ‒ 9.1% and 7.7%, respectively. Among Gram-positive pathogens, GBS displayed 100% penicillin susceptibility and E. faecalis showed 92.9% susceptibility to ampicillin.Conclusions. E. coli is unsurprisingly the most common cause of UTI in pregnancy in KwaZulu-Natal. Susceptibility to ceftriaxone and nitrofurantoin remains good. Among Gram positives, GBS is prevalent and susceptible to penicillin, while E. faecalis is susceptible to ampicillin. As antimicrobial resistance evolves, routine surveillance is necessary to modify recommended empirical antibiotic use

Antimicrobial susceptibility of bacterial uropathogens in a South African regional hospital

Background: Urinary tract infections are common bacterial infections affecting millions worldwide. Although treatment options for urinary tract infections are well established, with ciprofloxacin long considered one of the antibiotics of choice, increasing antibiotic resistance may delay the initiation of appropriate therapy. While this increase in antimicrobial resistance has been demonstrated in multiple studies around the world, there is a dearth of information from developing countries. Objective: This study aimed to describe the antimicrobial susceptibility patterns of commonly isolated bacterial uropathogens in a South African hospital. Methods: Antimicrobial susceptibility data of isolates obtained from urine specimens at the RK Khan Hospital, a regional hospital in KwaZulu-Natal, South Africa, between January 2018 and December 2020 were retrieved from the hospital’s laboratory information system and analysed to determine the differences in resistance rates between the most frequently isolated bacterial uropathogens. Results: Of the 3048 bacterial urinary pathogens isolated between 2018 and 2020, Escherichia coli (1603; 53%) was the most common, followed by Klebsiella spp. (437; 14%). Both E. coli and Klebsiella spp. showed high rates of resistance to amoxicillin/clavulanic acid (29.8% and 42.3%) and ciprofloxacin (37.7% and 30.4%). Nitrofurantoin resistance was low among E. coli (6.2%) but high among Klebsiella spp. (61.3%). Conclusion: E. coli and Klebsiella spp. in this study were highly resistant to amoxicillin/clavulanic acid and ciprofloxacin, two of the frequently prescribed oral treatment options. What this study adds: This study highlights the importance of regular local antimicrobial resistance surveillance to inform appropriate empiric therapy

Surveillance and comparison of antimicrobial susceptibility patterns of ESKAPE organisms isolated from patients with bacteraemia in South Africa, 2016 - 2017

Background. In South Africa (SA), the National Department of Health has developed an Antimicrobial Resistance National Strategy Framework document to manage antimicrobial resistance (AMR). One of the strategic objectives is to optimise surveillance and early detection of AMR. At the National Institute for Communicable Diseases (NICD), an analysis of selected organisms and antimicrobial agents from both the public and the private sectors was conducted.Objectives. The relevance of surveillance for AMR is increasingly recognised in the light of global action plans to combat resistance. In this report, we present an overview of ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp.) organisms and Escherichia coli reported from public and private sector laboratories in SA for the period 2016 - 2017.Methods. Antimicrobial susceptibility testing (AST) profiles on selected ESKAPE organisms and E. coli isolated from blood cultures from the public and private sectors in 2016 and 2017 were analysed. AST data were extracted from a web-based electronic platform created by the NICD. Drug-bug combinations following the World Health Organization’s Global Antimicrobial Surveillance System guidelines were included in the analysis.Results. A total of 28 920 ESKAPE organisms and E. coli were reported in 2016 and 32 293 in 2017 across the two health sectors. Proportions of some organisms differed between the two health sectors, such as E. coli (19% in the public sector and 36% in the private sector), A. baumannii (14% public and 4% private), P. aeruginosa (7% public and 11% private) and S. aureus (27% public and 17% private). Susceptibility data indicated changing patterns in both sectors towards an increase in non-susceptibility to carbapenems in K. pneumoniae (p<0.01). However, we demonstrated an increase in susceptibility to cloxacillin in S. aureus (p<0.01) in both sectors.Conclusions. The key clinically important finding is the rapidly decreasing carbapenem susceptibility among Enterobacteriaceae reported in SA, irrespective of sector. In addition, the analysis provides information that could be used to monitor the effectiveness of interventions implemented at a national level under the guidance and direction of the national AMR framework.

Difficult to quit smoking beyond “nicotine dependence”: a preliminary survey among adult male smokers in Felda Bukit Goh,Kuantan Pahang, Malaysia

Background: The vast majority of smokers want to quit and most make repeated attempts to do so. Although, effective treatment for nicotine dependence (ND) is present now, repeatedly fail to quit is still a common issue among smokers because of beyond nicotine addiction. Objective: To measure nicotine dependence (ND) level among adult male smokers and influences of socio-economic (SE) characteristics on ND and failing to quit smoking. Methods: A cross-sectional descriptive and analytical study was conducted in 2015 among 156 current adult male smokers in Kuantan, Malaysia. Socio-demographic and economic status, history of smoking and quitting attempt within 12 months and reasons for failing quit were identified by using a self-administered questionnaire. Level of nicotine dependence was assessed by validated Malay version of Fagerstrom Test for Nicotine Dependence questionnaires. Influence of socio-demographic and economic status on attempt to quit smoking and level of ND was analyzed. Results: Prevalence of low, moderate and high nicotine dependence level were 69.9%, 28.2% and 1.9% respectively. Among them, 55.1% were tried to quit smoking during 12 months. The most of reasons to fail quit attempt were nicotine addiction (69.8%) followed by uncomfortable/ tension/ not alert (10.5%), peer smoking/ social (10.5%), feel sleepy (7.9%) and desire to eat a lot (1.3%). Married smokers (56.6%) aged 31-40 years old (66%) with secondary education (52.9%) , private employee (68.3%), 1000-3000 RM family income per month (58.1%), and low ND score (59.6%) were tried to quit attempt and failed to quit. Smokers with low mean ND score (2.93) were attempted to quit significantly than those with high mean ND score (3.73). Conclusion: Nicotine dependence as a main reason for failing to quit smoking was confirmed in the study; however, influence of socio-demographic and economic characteristics was highlighted to consider in plan for successful quit smoking

Mental health assessment among staff working in an institution in Kuantan, Pahang, Malaysia: does designation of workplace determine it

The prevalence of work-related mental health problem is increasing trends in Malaysia. Among adult population, 12% suffered mental illness such as anxiety, stress,depression and schizophrenia. Majority of them are still working. Mental health assessment among staff is an entry point in providing appropriate mental health care to reduce mental health illness and its related social and behavior problems

A meta-analysis on the accuracy of dengue diagnostic tests used for point-of-care testing (POCT) in ASEAN patients

Introduction: ASEAN countries are included in the 30 most highly dengue endemic countries in the world. Evaluation of the accuracy of dengue diagnostic tests is essential for clinical management, surveillance, control activities and vaccine development. Aim of this study is to review the accuracy of diagnosis tests used for POCT for dengue infection. Methods: The accuracy results of 31 dengue diagnosis tests in 5308 ASEAN patients except Brunei were extracted from 14 articles published within 2007 and 2014. Rapid diagnosis tests (RDT) and WHO-Clinical criteria were considered for POCT. ELISA tests with/without WHO-Clinical criteria were included in meta-analysis. Pooled sensitivity (SN) and specificity (SP) were computed. Egger-bias was analysed for publication bias. Results: Pooled (range) SN of NS1(RDT) , IgM/IgG(RDT) , NS1+IgM/IgG (RDT) and WHO-Clinical criteria were 65% (44-79), 14% (3-50) ,80% (69-86) and 93% (80-97) while SP (range) of those tests were 99% (96-100), 97% (93-99), 96% (84-98) and 34% (20-57 )respectively. Pooled (range) of SN and SP of NS1 (ELISA) were 64% (45-82) and 99% (93-100. SN /SP (95% CI) of IgM/IgG (ELISA) were 50% (40-60) / 100% (96-100) and those of NS1+IgM/IgG (ELISA) were 94% (89-97)/92 % (81-97) and those of NS1+IgM/IgG (ELISA) with WHO -Clinical criteria were 91% (86-95)/ 94 % (84-98) respectively. Egger-bias was significant (p<0.0001). Discussion and conclusion: Both RDT and ELISA tests have high SP to rule in dengue diagnosis. Wide range of SN value (WHO-Clinical Criteria vs IgM/IgG RDT) highlighted to improve SN of the tests for ruling out. Added value of dengue epidemic information in the accuracy of the tests should be verified. A multi-centred study with a standardized protocol should be conducted for diagnostic test accuracy variation for POCT among ASEAN patients