Potential for Maternally Administered Vaccine for Infant Group B Streptococcus.

BACKGROUND: Natural history studies have correlated serotype-specific anti-capsular polysaccharide (CPS) IgG in newborns with a reduced risk of group B streptococcal disease. A hexavalent CPS-cross-reactive material 197 glycoconjugate vaccine (GBS6) is being developed as a maternal vaccine to prevent invasive group B streptococcus in young infants. METHODS: In an ongoing phase 2, placebo-controlled trial involving pregnant women, we assessed the safety and immunogenicity of a single dose of various GBS6 formulations and analyzed maternally transferred anti-CPS antibodies. In a parallel seroepidemiologic study that was conducted in the same population, we assessed serotype-specific anti-CPS IgG concentrations that were associated with a reduced risk of invasive disease among newborns through 89 days of age to define putative protective thresholds. RESULTS: Naturally acquired anti-CPS IgG concentrations were associated with a reduced risk of disease among infants in the seroepidemiologic study. IgG thresholds that were determined to be associated with 75 to 95% reductions in the risk of disease were 0.184 to 0.827 µg per milliliter. No GBS6-associated safety signals were observed among the mothers or infants. The incidence of adverse events and of serious adverse events were similar across the trial groups for both mothers and infants; more local reactions were observed in the groups that received GBS6 containing aluminum phosphate. Among the infants, the most common serious adverse events were minor congenital anomalies (umbilical hernia and congenital dermal melanocytosis). GBS6 induced maternal antibody responses to all serotypes, with maternal-to-infant antibody ratios of approximately 0.4 to 1.3, depending on the dose. The percentage of infants with anti-CPS IgG concentrations above 0.184 µg per milliliter varied according to serotype and formulation, with 57 to 97% of the infants having a seroresponse to the most immunogenic formulation. CONCLUSIONS: GBS6 elicited anti-CPS antibodies against group B streptococcus in pregnant women that were transferred to infants at levels associated with a reduced risk of invasive group B streptococcal disease. (Funded by Pfizer and the Bill and Melinda Gates Foundation; C1091002 ClinicalTrials.gov number, NCT03765073.).

Surviving Sepsis in the Intensive Care Unit: The Challenge of Antimicrobial Resistance and the Trauma Patient.

Sepsis in the intensive care unit (ICU) presents a great challenge to any critical care clinician. Patients admitted to the ICU are especially vulnerable to sepsis due to the nature of the underlying pathology that warranted admission to the ICU and deranged physiological function coupled with invasive procedures. Nosocomial infections are common in patients admitted to the ICU, and with these infections come the burden of multidrug-resistant organisms. Antimicrobial resistance (AMR) is now a global emergency that warrants the attention of every health-care professional. AMR has escalated to epic proportions and solutions to this problem are now a matter of "life and death." The ICU also represents the "breeding ground" of antibiotic-resistant organisms due to the high broad-spectrum antibiotic consumption. Many would argue that broad-spectrum antimicrobials are overprescribed in this patient population, but do all patients admitted to the ICU warrant such therapy? Is there evidence that narrower-spectrum antimicrobial agents can be employed in specific ICU populations coupled with surveillance strategies? The aims of this review are to focus on strategies with the aim of optimizing antimicrobial use within ICUs, and to highlight the importance of differentiating ICU populations with regard to the use of antimicrobial agents.

Antimicrobial resistance and antimicrobial stewardship in South Africa: a survey of healthcare workers in academic and nonacademic hospitals.

Objective: Antimicrobial stewardship programmes (ASPs) facilitate appropriate antimicrobial use and require contextualization for optimal functioning. We aimed to investigate perceptions of and antimicrobial resistance (AMR) and ASPs among healthcare workers in academic and nonacademic hospitals. Design: Cross-sectional survey. Setting: Three academic (Charlotte Maxeke Johannesburg Academic, Inkosi Albert Luthuli, Tygerberg) and three nonacademic hospitals (Leratong, Prince Mshiyeni Memorial, and Paarl) in South Africa from January to June 2022. Participants: Doctors, nurses, and pharmacists. Methods: Voluntary questionnaire using Google Forms, encompassing AMR, ASPs, and selected discipline-specific components. Results: Participants comprised 79 doctors (50 academic), 178 nurses (169 academic), and 21 pharmacists (18 academic) and were female predominant. AMR was a problem in academic hospitals (74.7% vs 51.2%, p 0.004); 73.5% overall reported inappropriate antimicrobial use as a major contributor. Adequate education on antimicrobials occurred in only 36.4% overall. Microbiological testing guided therapy more often in nonacademic settings (80.0% vs 50.2%, p <0.001). In both settings, antimicrobial availability drove selection in 48.2%. Overall, ASPs improved patient care (89.8%) and reduced antimicrobial use (86.9%), although felt to override prescriber autonomy in academic settings (29.4% vs 7.5%, p 0.007), mainly among nurses. Only 50.2% reported successful local ASPs. A minority of pharmacists (20.0%) reported sufficient hospital support for ASPs. Education, involvement of infection control staff, and inclusion of nurses in ASPs were most impactful on AMR. Conclusion: Selected healthcare worker perspectives differ by category and setting and can be targeted to improve ASPs. Further studies should target a higher number of clinical staff in both settings.

Antimicrobial Stewardship in Public-Sector Hospitals in KwaZulu-Natal, South Africa.

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.

Mobile genetic elements-mediated Enterobacterales-associated carbapenemase antibiotic resistance genes propagation between the environment and humans: A One Health South African study.

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 blaOXA-181, blaOXA-48, blaOXA-484, blaNDM-1, and blaGES-5 genes. Multiple species/clones carried blaOXA-48 and blaNDM-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 ß-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.

First genome sequence of Aeromonas hydrophilia novel sequence type 658 strain isolated from livestock in South Africa.

OBJECTIVES: The underlying resistance mechanisms, defence systems, mobilome, virulome, clonality and global phylogenetic relationship of a novel sequence type (ST) 658 Aeromonas hydrophilia (A34a) isolated from a pig abattoir in South Africa was determined using whole-genome sequence (WGS) technology. METHODS: Following isolation on chromogenic agar (CHROMID® CARBA SMART), microbial identification and antibiotic susceptibility testing were performed using a VITEK®2 platform. Genotyping involved WGS performed with an Illumina MiSeq platform. RESULTS: The antibiotic resistome agreed with the resistance phenotype of the isolate and included antibiotic resistance determinants for ß-lactams (blaCPHA3 and blaOXA-724). BLASTn analysis of resistome-encoding contigs affirmed chromosomally-mediated resistance. BURST algorithmic analysis identified the novel ST658 as a satellite variant. Virulome analysis predicted virulence genes of Aeromonas whose expression are critical for establishing infection in the host. Global phylogenomic analyses showed strain A34a is closely related to two international isolates from Sri Lanka (Ae25) and the USA (RU34A), although there is little to suggest that it was imported from abroad. CONCLUSION: This is the first report on the genomic analysis of a novel ST658 A. hydrophilia, offering useful insights into its pathogenicity and global phylogenetics.

Serum Cryptococcal Antigen Testing in Immunosuppressed HIV-positive Children and Adolescents.

OBJECTIVES: Describe the epidemiology of immunocompromised HIV-infected pediatric (children and adolescents ≤ 19 years) and adults (> 19 years) with positive serum cryptococcal antigen lateral flow assay (CrAg-LFA) in KwaZulu-Natal. DESIGN: Retrospective review of laboratory-based database and clinical charts. METHODS: A review of the National Health Laboratory Services database of all serum CrAg-LFA performed in KwaZulu-Natal between June 2015 and December 2016 and comparison of the epidemiology of pediatric and adult patients was conducted. A reflex serum CrAg-LFA (IMMY CrAg-LFA) was performed on samples with CD4 counts < 100 cells/µL. Charts of all pediatric patients with a positive CrAg-LFA at Prince Mshiyeni Memorial Hospital were reviewed and 1-year outcome assessed. RESULTS: A total of 22,741 laboratory records were retrieved, and 1140 records were removed because of duplicate entries (1074) and insufficient data (64). There was a statistically significant difference in the incidence of positive CrAg-LFA in pediatrics and adults, respectively [40 (3.5%) versus 1194 (5.8%), P = 0.001]. The incidence of positive CrAg-LFA in Ethekwini district was 59 and 56 cases per 100,000 persons in adolescents 10-14 years and 15-19 years, respectively. Six of the 8 patients with available treatment history were on antiretroviral treatment (ART) with immune failure at the time of CrAg-LFA testing. CONCLUSIONS: Severe immune suppression in adolescents on ART is a risk factor for cryptococcal antigenemia. A concerted effort to timeously manage ART failure in adolescents with appropriate changing of ART regimens is urgently warranted.

Pathogenomic Analysis of a Novel Extensively Drug-Resistant Citrobacter freundii Isolate Carrying a blaNDM-1 Carbapenemase in South Africa.

Pathogenomic analysis was performed on a novel carbapenem-resistant Citrobacter freundii isolate (H2730R) from a rectal swab of an adult male patient admitted to a tertiary hospital, Durban, South Africa. H2730R was identified using selective media and API 20e kit. Confirmatory identification and antibiotic susceptibility testing were performed using the VITEK II. H2730R was whole-genome sequenced on the Illumina MiSeq platform. H2730R was resistant to all tested antibiotics except tigecycline and was defined as ST498 by the C. freundii multilocus sequence typing (MLST) database. The estimated pathogenic potential predicted a higher probability (Pscore ≈ 0.875), supporting H2730R as a human pathogen. H2730R harbored 25 putative acquired resistance genes, 4 plasmid replicons, 4 intact prophages, a class 1 integron (IntI1), 2 predominant insertion sequences (IS3 and IS5), numerous efflux genes, and virulome. BLASTn analysis of the blaNDM-1 encoding contig (00022) and its flanking sequences revealed the blaNDM-1 was located on a plasmid similar to the multireplicon p18-43_01 plasmid reported for the spread of carbapenem resistance in South Africa. Phylogenomic analysis showed clustering of H2730R with CF003/CF004 strains in the same clade, suggesting a possible association between C. freundii strains/clones. Acquiring the p18-43_01 plasmid containing blaNDM-1, the diversity, and complex resistome, virulome, and mobilome of this pathogen makes its incidence very worrying regarding mobilized resistance. This study presents the background genomic information for future surveillance and tracking of the spread of carbapenem-resistant Enterobacteriaceae in South Africa.

Comparative Pathogenomics of Aeromonas veronii from Pigs in South Africa: Dominance of the Novel ST657 Clone.

The pathogenomics of carbapenem-resistant Aeromonas veronii (A. veronii) isolates recovered from pigs in KwaZulu-Natal, South Africa, was explored by whole genome sequencing on the Illumina MiSeq platform. Genomic functional annotation revealed a vast array of similar central networks (metabolic, cellular, and biochemical). The pan-genome analysis showed that the isolates formed a total of 4349 orthologous gene clusters, 4296 of which were shared; no unique clusters were observed. All the isolates had similar resistance phenotypes, which corroborated their chromosomally mediated resistome (blaCPHA3 and blaOXA-12) and belonged to a novel sequence type, ST657 (a satellite clone). Isolates in the same sub-clades clustered according to their clonal lineages and host. Mobilome analysis revealed the presence of chromosome-borne insertion sequence families. The estimated pathogenicity score (Pscore ≈ 0.60) indicated their potential pathogenicity in humans. Furthermore, these isolates carried several virulence factors (adherence factors, toxins, and immune evasion), in different permutations and combinations, indicating a differential ability to establish infection. Phylogenomic and metadata analyses revealed a predilection for water environments and aquatic animals, with more recent reports in humans and food animals across geographies, making A. veronii a potential One Health indicator bacterium.

Genomic Analysis of Carbapenemase-Producing Extensively Drug-Resistant Klebsiella pneumoniae Isolates Reveals the Horizontal Spread of p18-43_01 Plasmid Encoding blaNDM-1 in South Africa.

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 ß-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 blaNDM-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 blaNDM-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.

Antimicrobial stewardship in South Africa: a scoping review of the published literature.

OBJECTIVES: To map published data of antimicrobial stewardship (AMS) interventions that are currently being carried out in hospitals and clinics in the public and private health sectors of South Africa in line with the antimicrobial resistance (AMR) strategy of South Africa. METHODS: A systematic scoping review was conducted to identify AMS initiatives in the public and private health sectors of South Africa for the period 1 January 2000 to 31 March 2019. An electronic search of databases was made including PubMed, Scopus, a key medical journal (South African Medical Journal), University of KwaZulu-Natal (UKZN) WorldCat iCatalogue and AMR networks: Federation of Infectious Diseases Societies in South Africa (FIDSSA). Reference lists of published articles were also reviewed for inclusion. Keywords included 'antimicrobial antibiotic stewardship South Africa'. FINDINGS: Of a total of 411 articles, using a stepwise screening process, 18 articles were selected for inclusion in the review. The interventions/initiatives were divided into four broad categories: (i) AMS intervention: prescription audits and usage; (ii) AMS intervention: education and its impact; (iii) other AMS interventions; and (iv) the role of different healthcare professionals in AMS. CONCLUSIONS: The data identifies a need for and the value of AMS in both the public and private health sectors of South Africa. Initiatives are carried out across both sectors but more attention needs to be focused on AMS implementation in line with the National AMR Strategy of South Africa. Collaboration between the different sectors will aid in overcoming the AMR challenge.

Antibiotic resistance trends of ESKAPE pathogens in Kwazulu-Natal, South Africa: A five-year retrospective analysis.

BACKGROUND: To combat antimicrobial resistance, the World Health Organization developed a global priority pathogen list of antibiotic-resistant bacteria for prioritisation of research and development of new, effective antibiotics. OBJECTIVE: This study describes a five-year resistance trend analysis of the ESKAPE pathogens: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp., from Kwazulu-Natal, South Africa. METHODS: This retrospective study used National Health Laboratory Services data on 64 502 ESKAPE organisms isolated between 2011 and 2015. Susceptibility trends were ascertained from minimum inhibitory concentrations and interpreted using Clinical and Laboratory Standards Institute guidelines. RESULTS: S. aureus was most frequently isolated (n = 24, 495, 38%), followed by K. pneumoniae (n = 14, 282, 22%). Decreasing rates of methicillin-resistant S. aureus (28% to 18%, p < 0.001) and increasing rates of extended spectrum beta-lactamase producing K. pneumoniae (54% to 65% p < 0.001) were observed. Carbapenem resistance among K. pneumoniae and Enterobacter spp. was less than 6% during 2011-2014, but increased from 4% in 2014 to 16% in 2015 (p < 0.001) among K. pneumoniae. P. aeruginosa increased (p = 0.002), but resistance to anti-pseudomonal antimicrobials decreased from 2013 to 2015. High rates of multi-drug resistance were observed in A. baumanni (> 70%). CONCLUSION: This study describes the magnitude of antimicrobial resistance in KwaZulu-Natal and provides a South African perspective on antimicrobial resistance in the global priority pathogen list, signalling the need for initiation or enhancement of antimicrobial stewardship and infection control measures locally.

Whole-Genome Sequence of a Novel Sequence Type 3136 Carbapenem-Resistant Klebsiella pneumoniae Strain Isolated from a Hospitalized Patient in Durban, South Africa.

Here, we describe the genome sequence of a novel sequence type 3136 (ST3136) Klebsiella pneumoniae strain isolated in South Africa. The 5,574,236-bp genome harbored 23 resistance determinants and 12 virulence factors that are of cardinal importance to infections. The genomics of Klebsiella pneumoniae offer valuable insights into its pathogenicity.

Empirical antimicrobial therapy for probable v. directed therapy for possible ventilator-associated pneumonia in critically injured patients.

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.

Microbiological surveillance and antimicrobial stewardship minimise the need for ultrabroad-spectrum combination therapy for treatment of nosocomial infections in a trauma intensive care unit: an audit of an evidence-based empiric antimicrobial policy.

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.