We, (1) studied carbapenem-resistant Enterobacterales (CRE) in the environment, humans, and animals, within the same geographical area and, (2) delineated the isolates' resistome, mobilome, virulome, and phylogeny. Following ethical approval, 587 samples (humans = 230, pigs = 345, and water = 12) were collected and cultured on CRE selective media. Confirmatory identification and antibiotic susceptibility testing were performed using the VITEK 2 automated platform. The resistomes, virulomes, mobilomes, and phylogenies were ascertained by whole genome sequencing. Nineteen (3.2%), i.e., 15/19 humans and 4/19 environmental, but no pig, CRE were obtained. CREs included Klebsiella pneumoniae 9/19 (47%), Enterobacter hormaechei 6/19 (32%), Klebsiella quasipneumoniae 2/19 (11%), a novel ST498 Citrobacter freundii 1/19 (5%) and Serratia marcescens 1/19 (5%). Eleven isolates were extensively drug-resistant; eight were multidrug-resistant. Sixteen CRE harbored the bla_OXA-181, bla_OXA-48, bla_OXA-484, bla_NDM-1, and bla_GES-5 genes. Multiple species/clones carried bla_OXA-48 and bla_NDM-1 carbapenemase-encoding genes with respective mobile genetic elements (MGEs). The IncFIB(K) plasmid replicon was found in most human K. pneumoniae strains (7/9) and all environmental K. quasipneumoniae isolates; most K. pneumoniae produced OXA-181 (5/9). The (Col440I) plasmid replicon, identified in 11 (26.82%) isolates, mainly E. hormaechei (n = 6), predominated both sectors. Most β-lactamase-encoding genes were associated with class 1 integrons IntI1, insertion sequences (IS) (IS91, IS5075, IS30, IS3000, IS3, IS19, ISKpn19, IS5075) and transposons (Tn3). The IncL/M(pMU407) and IncL/M(pOXA48) plasmid replicons were found exclusively in K. pneumoniae; all but one of these strains produced OXA-181. Also, the Klebsiella spp. harbored 80 virulence genes. Phylogenomic clustered identified isolates with other carbapenemase-producing K. pneumoniae, E. hormaechei, S. marcescens, and C. freundii from different South African sources (animals, environment, and humans). We delineated the resistome, mobilome, virulome, and phylogeny of carbapenemase-producing Enterobacterales in humans and environment, highlighting antibiotic resistance genes propagation via MGEs across sectors, emphasizing a One Health approach to AMR.

The African Journal of Laboratory Medicine focuses on the role of the laboratory and its professionals in the clinical and public healthcare sectors, and is specifically based on an African frame of reference.

Whole-genome sequence (WGS) analyses were employed to investigate the genomic epidemiology of extensively drug-resistant Klebsiella pneumoniae strains, focusing on the carbapenem resistance-encoding determinants, mobile genetic support, clonal and epidemiological relationships. A total of ten isolates were obtained from patients admitted to the intensive care unit (ICU) in a public hospital in South Africa. Five isolates were from rectal swabs of colonized patients and five from blood cultures of patients with invasive carbapenem-resistant infections. Following microbial identification and antibiotic susceptibility tests, the isolates were subjected to WGS on the Illumina MiSeq platform. All the isolates showed genotypic resistance to tested β-lactams (NDM-1, OXA-1, CTX-M-15, TEM-1B, SHV-1) and other antibiotics. All but one isolate belonged to the ST152 with a novel sequence type, ST3136, differing by a single-locus variant. The isolates had the same plasmid multilocus sequence type (IncF[K12:A-:B36]) and capsular serotype (KL149), supporting the epidemiological linkage between the clones. Resistance to carbapenems in the 10 isolates was conferred by the bla_NDM-1 mediated by the acquisition of multi-replicon [ColRNAI, IncFIB(pB171), Col440I, IncFII, IncFIB(K) and IncFII(Yp)] p18-43_01 plasmid. These findings suggest that the acquisition of bla_NDM-1-bearing plasmid structure (p18-43_01), horizontal transfer and clonal dissemination facilitate the spread of carbapenemases in South Africa. This emphasizes the importance of targeted infection control measures to prevent dissemination.

Background. Nosocomial infections are a major cause of morbidity in the critically injured, and the incidence of resistant strains of bacteria is increasing. Management requires a strategy that achieves accurate empiric cover without antibiotic overuse − a goal that may be achieved by surveillance and antibiotic stewardship. Objectives. With the aim of minimising the use of empirical ultrabroad-spectrum combination antimicrobial prescriptions and reducing bacterial resistance, the level I Trauma Intensive Care Unit (TICU) at Inkosi Albert Luthuli Central Hospital (IALCH) in Durban employs stewardship and an antimicrobial policy based on surveillance. This study was undertaken with three aims: (i) to describe the spectrum and sensitivities of nosocomial pathogens in a level I TICU; (ii) to ascertain, based on surveillance data, how frequently initial empiric choice of antimicrobials was correct; and (iii) to determine how frequently ultrabroad-spectrum antimicrobials were prescribed and were actually necessary. Methods. Over a 12-month period, all critically injured patients who underwent mechanical ventilation in the TICU were identified from a prospectively gathered database. Information regarding every specimen submitted to the National Health Laboratory Services (NHLS) situated at IALCH was extracted from the laboratory computer database. For each patient, bacterial isolates and antimicrobial susceptibility were identified using standard laboratory techniques. Empiric prescriptions for presumed nosocomial sepsis were identified from the hospital’s computerised patient record system and compared with culture results. Acinetobacter species were regarded as colonisers and treatment not offered unless this was the sole isolate in the presence of signs of severe sepsis. Results. Of 227 patients, 106 (46.6%) had 136 culture-positive isolates with a total of 323 pathogens (201 Gram-negative, 119 Gram-positive, 3 Candida albicans). There were 19 species of Gram-negative pathogens, of which 56% comprised Enterobacteriaceae. Extended spectrum beta-lactamase (ESBL) production was found in 6/31 (19%) Escherichia coli coli and 6/24 (25%) Klebsiella isolates. Staphyloccocal species accounted for 60% of the Gram-positive isolates, of which 18 were methicillin-resistant Staphylococcus aureus (MRSA). All Candida isolates were sensitive to fluconazole. One hundred and one empiric and 14 directed prescriptions were issued. Despite positive cultures, antimicrobials were not prescribed for 21 patients who had no evidence of sepsis. Excluding multidrug-resistant Acinetobacter isolates, there were 87 (93.5%) appropriate and 6 (6.5%) incorrect prescriptions. Ultrabroad-spectrum combination therapy (U-bSCT) was employed for 11 patients but was necessary in only 2. Conclusions. When combined with regular bacterial surveillance, antimicrobial stewardship allows accurate empiric antimicrobial prescription with minimal need for ultrabroad-spectrum combination therapy. This policy can potentially reduce the emergence of multidrug-resistant pathogens, precluding the need for broad-spectrum antimicrobials and the attendant problems of overuse.

Antimicrobial resistance (AMR) is a serious global public-health threat. Evidence suggests that antimicrobial stewardship (AMS) is a valuable tool to facilitate rational antibiotic use within healthcare facilities. A cross-sectional situational analysis using a questionnaire was conducted to determine the current status of antimicrobial stewardship (AMS) activities in all public-sector hospitals in KwaZulu-Natal (KZN). The survey had a 79% (57, N = 72) response rate. A total of 75% of hospitals had an antimicrobial stewardship committee (AMSC), 47% (20, N = 43) had a formal written statement of support from leadership, and 7% (3, N = 43) had budgeted financial support. Only 37% (16, N = 43) had on-site or off-site support from a clinical microbiologist, and 5% (2, N = 43) had an on-site infectious disease (ID) physician. Microbiologist input on pathogen surveillance data (aOR: 5.12; 95% CI: 4.08–22.02; p-value = 0.001) and microbiological investigations prior to the commencement of antibiotics (aOR: 5.12; 95% CI: 1.08–42.01; p-value = 0.041) were significantly associated with having either on- or off-site microbiology support. Respondents that had a representative from microbiology on the AMSC were significantly associated with having and interrogating facility-specific antibiograms (P = 0.051 and P = 0.036, respectively). Those facilities that had access to a microbiologist were significantly associated with producing an antibiogram (aOR: 4.80; 95% CI: 1.25–18.42; p-value = 0.022). Facilities with an ID physician were significantly associated with having a current antibiogram distributed to prescribers within the facility (P = 0.010) and significantly associated with sending prescribers personalized communication regarding improving prescribing (P = 0.044). Common challenges reported by the facilities included suboptimal hospital management support; a lack of clinicians, pharmacists, nurses, microbiologists, and dedicated time; the lack of a multidisciplinary approach; low clinician buy-in; inadequate training; a lack of printed antibiotic guidelines; and financial restrictions for microbiological investigations. The survey identified the need for financial, IT, and management support. Microbiology and infectious disease physicians were recognized as scarce human resources.

Background. Ventilator-associated pneumonia (VAP) has recently been classified as possible or probable. Although direct attributable mortality has been difficult to prove, delay in instituting appropriate therapy has been reported to increase morbidity and mortality. Recent literature suggests that in possible VAP, instituting directed therapy while awaiting microbiological culture does not prejudice outcome compared with best-guess empirical therapy. Objectives. To ascertain outcomes of directed v. empirical therapy in possible and probable VAP, respectively. Methods. Endotracheal aspirates were obtained from patients with suspected VAP. Those considered to have possible VAP were given directed therapy following culture results, whereas patients with more convincing evidence of VAP were classed as having probable VAP and commenced on empirical antimicrobials based on microbiological surveillance. Results. Pneumonia was suspected in 106 (36.8%) of 288 patients admitted during January - December 2014. Of these, 13 did not fulfil the criteria for VAP. Of the remaining 93 (32.2%), 31 (33.3%) were considered to have probable and 62 (66.7%) possible VAP. The former were commenced on empirical antimicrobials, with 28 (90.3%) receiving appropriate therapy. Of those with possible VAP, 34 (54.8%) were given directed therapy and in 28 (45.2%) no antimicrobials were prescribed. Of the latter, 24 recovered without antimicrobials and 4 died, 3 from severe traumatic brain injury and 1 due to overwhelming intra-abdominal sepsis. No death was directly attributable to failure to treat VAP. No significant difference in mortality was found between the 34 patients with possible VAP who were commenced on directed therapy and the 31 with probable VAP who were commenced on empirical antimicrobials (p=0.75).Conclusions. Delaying antimicrobial therapy for VAP where clinical doubt exists does not adversely affect outcome. Furthermore, this policy limits the use of antimicrobials in patients with possible VAP following improvement in their clinical condition despite no therapy.