Clinical Efficacy and Safety of a Novel Antifungal, Fosmanogepix, in Patients with Candidemia Caused by Candida auris: Results from a Phase 2 Trial.

Fosmanogepix (FMGX), a novel antifungal available in intravenous (IV) and oral formulations, has broad-spectrum activity against pathogenic yeasts and molds, including fungi resistant to standard of care antifungals. This multicenter, open-label, single-arm study evaluated FMGX safety and efficacy for treatment of candidemia and/or invasive candidiasis caused by Candida auris. Eligible participants were ≥18 years, with established candidemia and/or invasive candidiasis caused by C. auris, (cultured within 120 h [for candidemia] or 168 h [for invasive candidiasis without candidemia] with accompanying clinical signs) and limited treatment options. Participants were treated with FMGX (≤42 days; loading dose: 1000 mg IV twice daily [Day 1], followed by 600 mg IV once daily [QD]). Switching to oral FMGX 800 mg QD was permitted from Day 4. Primary endpoint was treatment success (survival and clearance of C. auris from blood/tissue cultures without additional antifungals) at the end of the study treatment (EOST), assessed by an independent data review committee (DRC). Day 30 survival was a secondary endpoint. In vitro susceptibility of Candida isolates was assessed. Nine participants with candidemia (male:6, female:3; 21 to 76 years) in intensive care units in South Africa were enrolled; all received IV FMGX only. DRC-assessed treatment success at EOST and Day 30 survival were 89% (8/9). No treatment related adverse events or study drug discontinuations were reported. FMGX demonstrated potent in vitro activity against all C. auris isolates (MIC range: 0.008 to 0.015 µg/mL [CLSI]; 0.004-0.03 µg/mL [EUCAST]), with the lowest MICs compared to other antifungals tested. Thus, the results showed that FMGX was safe, well-tolerated, and efficacious in participants with candidemia caused by C. auris.

Development and internal validation of the HIV In-hospital Mortality Prediction (HIV-IMP) risk score.

BACKGROUND: Despite advances in availability and access to antiretroviral therapy (ART), HIV still ranks as a major cause of global mortality. Hence, the aim of this study was to develop and internally validate a risk score capable of accurately predicting in-hospital mortality in HIV-positive patients requiring hospital admission. METHODS: Consecutive HIV-positive patients presenting to the Charlotte Maxeke Johannesburg Academic Hospital adult emergency department between 7 July 2017 and 18 October 2018 were prospectively enrolled. Multivariate logistic regression was used to determine parameters for inclusion in the final risk score. Discrimination and calibration were assessed by means of the area under the receiver operating curve (AUROC) and the Hosmer-Lemeshow goodness-of-fit test, respectively. Internal validation was conducted using the regular bootstrap technique. RESULTS: The overall in-hospital mortality rate was 13.6% (n = 166). Eight predictors were included in the final risk score: ART non-adherence or not yet on ART, Glasgow Coma Scale < 15, respiratory rate > 20 breaths/min, oxygen saturation < 90%, white cell count < 4 × 109 /L, creatinine > 120 µmol/L, lactate > 2 mmol/L and albumin < 35 g/L. After internal validation, the risk score maintained good discrimination [AUROC 0.83, 95% confidence interval (CI): 0.78-0.88] and calibration (Hosmer-Lemeshow χ2 = 2.26, p = 0.895). CONCLUSION: The HIV In-hospital Mortality Prediction (HIV-IMP) risk score has overall good discrimination and calibration and is relatively easy to use. Further studies should be aimed at externally validating the score in varying clinical settings.

Maternal high-care and intensive care units in low- and middle-income countries.

Despite notable advancements in minimizing maternal mortality during recent decades, a pronounced disparity persists between high-income nations and low-to middle-income countries (LMICs), particularly in intensive and high-care for pregnant and postpartum individuals. This divergence is multifactorial and influenced by factors such as the availability and accessibility of community-based maternity healthcare services, the quality of preventive care, timeliness in accessing hospital or critical care, resource availability, and facilities equipped for advanced interventions. Complications from various conditions, including human immunodeficiency virus (HIV), unsafe abortions, puerperal sepsis, and, notably, the COVID-19 pandemic, intensify the complexity of these challenges. In confronting these challenges and deliberating on potential solutions, we hope to contribute to the ongoing discourse around maternal healthcare in LMICs, ultimately striving toward an equitable health landscape where every mother, regardless of geographic location or socioeconomic status, has access to the care they require and deserve. The use of traditional and innovative methods to achieve adequate knowledge, appropriate skills, location of applicable resources, and strong leadership is essential. By implementing and enhancing these strategies, limited-resource settings can optimize the available resources to promptly recognize the severity of illness in obstetric individuals, ensuring timely and appropriate interventions for mothers and children. Additionally, strategies that could significantly improve the situation include increased investment in healthcare infrastructure, effective resource management, enhanced supply chain efficiency, and the development and use of low-cost, high-quality equipment. Through targeted investments, innovations, efficient resource management, and international cooperation, it is possible to ensure that every maternal high-care and ICU unit, regardless of geographical location or socioeconomic status, has access to high-quality critical care to provide life-saving care.

Peri-operative pharmacokinetics of cefazolin prophylaxis during valve replacement surgery.

OBJECTIVE: There is little prospective data to guide effective dosing for antibiotic prophylaxis during surgery requiring cardiopulmonary bypass (CPB). We aim to describe the effects of CPB on the population pharmacokinetics (PK) of total and unbound concentrations of cefazolin and to recommend optimised dosing regimens. METHODS: Patients undergoing CPB for elective cardiac valve replacement were included using convenience sampling. Intravenous cefazolin (2g) was administered pre-incision and re-dosed at 4 hours. Serial blood and urine samples were collected and analysed using validated chromatography. Population PK modelling and Monte-Carlo simulations were performed using Pmetrics® to determine the fractional target attainment (FTA) of achieving unbound concentrations exceeding pre-defined exposures against organisms known to cause surgical site infections for 100% of surgery (100% fT>MIC). RESULTS: From the 16 included patients, 195 total and 64 unbound concentrations of cefazolin were obtained. A three-compartment linear population PK model best described the data. We observed that cefazolin 2g 4-hourly was insufficient to achieve the FTA of 100% fT>MIC for Staphylococcus aureus and Escherichia coli at serum creatinine concentrations ≤ 50 µmol/L and for Staphylococcus epidermidis at any of our simulated doses and serum creatinine concentrations. A dose of cefazolin 3g 4-hourly demonstrated >93% FTA for S. aureus and E. coli. CONCLUSIONS: We found that cefazolin 2g 4-hourly was not able to maintain concentrations above the MIC for relevant pathogens in patients with low serum creatinine concentrations undergoing cardiac surgery with CPB. The simulations showed that optimised dosing is more likely with an increased dose and/or dosing frequency.

"Acute Kidney Injury predictive models: advanced yet far from application in resource-constrained settings."

Acute kidney injury (AKI) remains a major cause of morbidity and mortality in hospitalized patients, particularly critically ill patients. It poses a public health challenge in resource-constrained settings due to high administrative costs. AKI is commonly misdiagnosed due to its painless onset and late disruption of serum creatinine, which is the gold standard biomarker for AKI diagnosis. There is increasing research into the use of early biomarkers and the development of predictive models for early AKI diagnosis using clinical, laboratory, and imaging data. This field note provides insight into the challenges of using available AKI prediction models in resource-constrained environments, as well as perspectives that practitioners in these settings may find useful.

Development and validation of a clinical prediction model of acute kidney injury in intensive care unit patients at a rural tertiary teaching hospital in South Africa: a study protocol.

INTRODUCTION: Acute kidney injury (AKI) is a decline in renal function lasting hours to days. The rising global incidence of AKI, and associated costs of renal replacement therapy, is a public health priority. With the only therapeutic option being supportive therapy, prevention and early diagnosis will facilitate timely interventions to prevent progression to chronic kidney disease. While many factors have been identified as predictive of AKI, none have shown adequate sensitivity or specificity on their own. Many tools have been developed in developed-country cohorts with higher rates of non-communicable disease, and few have been validated and practically implemented. The development and validation of a predictive tool incorporating clinical, biochemical and imaging parameters, as well as quantification of their impact on the development of AKI, should make timely and improved prediction of AKI possible. This study is positioned to develop and validate an AKI prediction tool in critically ill patients at a rural tertiary hospital in South Africa. METHOD AND ANALYSIS: Critically ill patients will be followed from admission until discharge or death. Risk factors for AKI will be identified and their impact quantified using statistical modelling. Internal validation of the developed model will be done on separate patients admitted at a different time. Furthermore, patients developing AKI will be monitored for 3 months to assess renal recovery and quality of life. The study will also explore the utility of endothelial monitoring using the biomarker Syndecan-1 and capillary leak measurements in predicting persistent AKI. ETHICS AND DISSEMINATION: The study has been approved by the Walter Sisulu University Faculty of Health Science Research Ethics and Biosafety Committee (WSU No. 005/2021), and the Eastern Cape Department of Health Research Ethics (approval number: EC 202103006). The findings will be shared with facility management, and presented at relevant conferences and seminars.

Predictors of prolonged hospital stay in HIV-positive patients presenting to the emergency department.

BACKGROUND: Prolonged hospitalization places a significant burden on healthcare resources. Compared to the general population, hospital length of stay (LOS) is generally longer in HIV-positive patients. We identified predictors of prolonged hospital length of stay (LOS) in HIV-positive patients presenting to an emergency department (ED). METHODS: In this cross-sectional study, HIV-positive patients presenting to the Charlotte Maxeke Johannesburg Academic Hospital adult ED were prospectively enrolled between 07 July 2017 and 18 October 2018. Data was subjected to univariate and multivariate logistic regression to determine parameters associated with a higher likelihood of prolonged hospital LOS, defined as ≥7 days. RESULTS: Among the 1224 participants that were enrolled, the median (IQR) LOS was 4.6 (2.6-8.2) days, while the mean (SD) LOS was 6.9 (8.2) days. On multivariate analysis of the data, hemoglobin <11 g/dL (OR 1.37, p = 0.032), Glasgow coma scale (GCS) <15 (OR 1.80, p = 0.001), creatinine >120 µmol/L (OR 1.85, p = 0.000), cryptococcal meningitis (OR 2.45, p = 0.015) and bacterial meningitis (OR 4.83, p = 0.002) were significantly associated with a higher likelihood of LOS ≥7 days, while bacterial pneumonia (OR 0.35, p = 0.000) and acute gastroenteritis (OR 0.40, p = 0.025) were significantly associated with a lower likelihood of LOS ≥7 days. CONCLUSION: Various clinical and laboratory parameters are useful in predicting prolonged hospitalization among HIV-positive patients presenting to the ED. These parameters may be useful in guiding clinical decision making and directing the allocation of resources.

Clinical utility of the BioFire FilmArray Blood Culture Identification panel in the adjustment of empiric antimicrobial therapy in the critically ill septic patient.

Sepsis and septic shock are key contributors to mortality in critically ill patients and thus prompt recognition and management thereof is central to achieving improved patient outcomes. Early initiation of appropriate antimicrobial therapy constitutes a crucial component of the management strategy and thus early identification of the causative pathogen is essential in informing antimicrobial therapeutic choices. The BioFire FilmArray blood culture identification (BCID) panel is a US Food and Drug Administration (FDA) approved rapid, multiplex polymerase chain reaction assay for use on positive blood cultures. This study evaluated its clinical utility in the intensive care unit (ICU) setting, in terms of amendment of empiric antimicrobial therapy in critically ill patients with sepsis. The assay proved useful in this setting as final results were made available to clinicians significantly earlier than with conventional culture methods. This, in turn, allowed for modification of empirical antimicrobial therapy to more appropriate agents in 32% of patients. Additionally, the use of the BioFire FilmArray BCID panel permitted the prompt implementation of additional infection prevention and control practices in a sizeable proportion (14%) of patients in the study who were harbouring multidrug resistant pathogens. These findings support the use of the BioFire FilmArray BCID panel as a valuable adjunct to conventional culture methods for the diagnosis and subsequent management of critically ill patients with sepsis.

Diagnostic accuracy of the BioFire FilmArray blood culture identification panel when used in critically ill patients with sepsis.

Sepsis accounts for high mortality rates in critical care units. Prompt and accurate identification of causative pathogens and initiation of appropriate antimicrobial therapy is critical for the appropriate management of patients in order to optimise clinical outcomes. The BioFire FilmArray blood culture identification (BCID) panel is a US Food and Drug Administration (FDA) approved rapid, multiplex polymerase chain reaction (PCR) assay that is able to identify a variety of bacteria, fungi and antimicrobial resistance determinants directly from positive blood cultures. The aim of this study was to evaluate the diagnostic performance of the BioFire FilmArray BCID panel against the gold standard of blood cultures. Seventy-eight positive blood cultures obtained from critically ill patients suspected of having sepsis were included in the study. Each bottle was processed with the BioFire FilmArray BCID panel as well as conventional culture methods. Diagnostic accuracy of the BioFire FilmArray BCID panel was determined. The assay demonstrated a high sensitivity and specificity for pathogen identification of 96.5% (95% CI, 91.3-99.0) and 99.7% (95% CI, 99.3-99.9), respectively. The findings of this study support the role of the BioFire FilmArray BCID panel in the management of critically ill patients with sepsis.

Profile of presentation of HIV-positive patients to an emergency department in Johannesburg, South Africa.

BACKGROUND: Despite improved availability and better access to antiretroviral therapy (ART), approximately 36% of human immunodeficiency virus (HIV)-positive South Africans are still not virally suppressed. OBJECTIVE: The aim of this study was to describe the patterns of presentation of HIV-positive patients to a major central hospital emergency department (ED). METHODS: In this prospectively designed study, consecutive HIV-positive patients presenting to the Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) adult ED were enrolled between 07 July 2017 and 18 October 2018. RESULTS: A total of 1224 participants were enrolled. Human immunodeficiency virus was newly diagnosed in 212 (17.3%) patients, 761 (75.2%) were on ART, 245 (32.2%) reported ART non-adherence, 276 (22.5%) had bacterial pneumonia, 244 (19.9%) had tuberculosis (TB), 86 (7.0%) had gastroenteritis, 205 (16.7%) required intensive care unit admission, 381 (31.1%) were admitted for ≥ 7 days and 166 (13.6%) died. With regard to laboratory parameters, CD4 cell count was < 100 cell/mm3 in 527 (47.6%) patients, the viral load (VL) was > 1000 copies/mL in 619 (59.0%), haemoglobin was < 11 g/dL in 636 (56.3%), creatinine was > 120 µmol/L in 294 (29.3%), lactate was > 2 mmol/L in 470 (42.0%) and albumin was < 35 g/L in 633 (60.8%). CONCLUSION: Human immunodeficiency virus-positive patients presenting to the CMJAH ED demonstrated a high prevalence of opportunistic infections, required a prolonged hospital stay and had high mortality rates. There is a need to improve the quality of ART services and accessibility to care.

Survival after Cardiac Arrest Secondary to Massive Pulmonary Embolism.

INTRODUCTION: It is estimated that the diagnosis of pulmonary embolism (PE) is missed in as many as 84% of all cases of PE. Cardiac arrest following PE is generally associated with poor outcomes. CASE REPORT: A 43-year-old man presented to the Emergency Department (ED) in cardiac arrest. Swelling of his right lower limb was noted on arrival. Point of care ultrasound was performed during ongoing cardiopulmonary resuscitation (CPR) and showed a thrombus in the right iliofemoral vein as well as dilatation of the right ventricle. Fibrinolytic therapy was initiated immediately and a return of spontaneous circulation (ROSC) was achieved 30 minutes later. The diagnosis of PE was finally confirmed on computed tomography pulmonary angiography once haemodynamic stability was achieved. The patient was thereafter transferred to the intensive care unit for postresuscitation care and further management. Several days later, he was discharged home neurologically intact and fully recovered. DISCUSSION: Since outcomes after cardiac arrest following PE are generally dismal, available and potentially life-saving interventions to restore pulmonary circulation should be rapidly implemented when PE is the likely cause of cardiac arrest.

Dosing antibiotic prophylaxis during cardiopulmonary bypass-a higher level of complexity? A structured review.

In highly invasive procedures such as open heart surgery, the risk of post-operative infection is particularly high due to exposure of the surgical field to multiple foreign devices. Adequate antibiotic prophylaxis is an essential intervention to minimise post-operative morbidity and mortality. However, there is a lack of clear understanding on the adequacy of traditional prophylactic dosing regimens, which are rarely supported by data. The aim of this structured review is to describe the relevant pharmacokinetic/pharmacodynamic (PK/PD) considerations for optimal antibiotic prophylaxis for major cardiac surgery including cardiopulmonary bypass (CPB). A structured review of the relevant published literature was performed and 45 relevant studies describing antibiotic pharmacokinetics in patients receiving extracorporeal CPB as part of major cardiac surgery were identified. Some of the studies suggested marked PK alterations in the peri-operative period with increases in volume of distribution (Vd) by up to 58% and altered drug clearances of up to 20%. Mechanisms proposed as causing the PK changes included haemodilution, hypothermia, retention of the antibiotic within the extracorporeal circuit, altered physiology related to a systemic inflammatory response, and maldistribution of blood flow. Of note, some studies reported no or minimal impact of the CPB procedure on antibiotic pharmacokinetics. Given the inconsistent data, ongoing research should focus on clarifying the influence of CPB procedure and related clinical covariates on the pharmacokinetics of different antibiotics during cardiac surgery. Traditional prophylactic dosing regimens may need to be re-assessed to ensure sufficient drug exposures that will minimise the risk of surgical site infections.

The Durban World Congress Ethics Round Table IV: health care professional end-of-life decision making.

INTRODUCTION: When terminal illness exists, it is common clinical practice worldwide to withhold (WH) or withdraw (WD) life-sustaining treatments. Systematic documentation of professional opinion and perceived practice similarities and differences may allow recommendations to be developed. MATERIALS AND METHODS: Speakers from invited faculty of the World Federation of Societies of Intensive and Critical Care Medicine Congress that took place in Durban (2013), with an interest in ethics, were approached to participate in an ethics round table. Key domains of health care professional end-of-life decision making were defined, explored by discussion, and then questions related to current practice and opinion developed and subsequently answered by round-table participants to establish the presence or absence of agreement. RESULTS: Agreement was established for the desirability for early goal-of-care discussions and discussions between health care professionals to establish health care provider consensus and confirmation of the grounds for WH/WD, before holding formal WH/WD discussions with patients/surrogates. Nurse and other health care professional involvement were common in most but not all countries/regions. Principles and practical triggers for initiating discussions on WH/WD, such as multiorgan failure, predicted short-term survival, and predicted poor neurologic outcome, were identified. CONCLUSIONS: There was majority agreement for many but not all statements describing health care professional end-of-life decision making.

National expenditure on health research in South Africa: what is the benchmark?

The Mexico (2004), Bamako (2008) and Algiers (2008) declarations committed the South African (SA) Ministry of Health to allocate 2% of the national health budget to research, while the National Health Research Policy (2001) proposed that the country budget for health research should be 2% of total public sector health expenditure. The National Health Research Committee has performed an audit to determine whether these goals have been met, judged by: (i) health research expenditure as proportions of gross expenditure on research and development (GERD) and the gross domestic product (GDP); and (ii) the proportion of the national health and Department of Health budgets apportioned to research. We found that total expenditure on health research in SA, aggregated across the public and private sectors, was R3.5 billion in 2009/10, equating to 16.7% of GERD. However, the total government plus science council spend on health research that year was only R729 million, equating to 3.5% of GERD (0.03% of the GDP) or 0.80% of the R91.4 billion consolidated government expenditure on health. We further found that R418 million was spent through the 2009/2010 Health Vote on health research, equating to 0.46% of the consolidated government expenditure on health or 0.9% of the R45.2 billion Health Vote. Data from other recent years were similar. Current SA public sector health research allocations therefore remain well below the aspirational goal of 2% of the national health budget. We recommend that new, realistic, clearly defined targets be adopted and an efficient monitoring mechanism be developed to track future health research expenditure.

The Durban World Congress Ethics Round Table Conference Report: II. Withholding or withdrawing of treatment in elderly patients admitted to the intensive care unit.

INTRODUCTION: Life-sustaining treatment (LST) limitation for elderly patients is highly controversial. In that context, it is useful to evaluate the attitudes to LST in the elderly among experienced intensive care unit (ICU) physicians with different backgrounds and cultures. METHODS: A panel of 22 international ICU physicians from 13 countries responded to a questionnaire related to withholding (WH) and withdrawing (WD) LST in elderly patients using a semi-Likert scale. RESULTS: Most experts disagree or strongly disagree (77%) that age should be used as the sole criterion for WH or WD LST, and almost all disagree (91%) that there should be a specific age for such decision making. However, the vast majority (91%) acknowledge that age should be an important consideration in conjunction with other factors. Disagreement for consideration of prioritizing the young over the old in normal ICU operations was reported in 68%, whereas in an emergency triage situation, disagreement dropped to 18%. CONCLUSIONS: There is a consensus among ICU physicians that age cannot be the sole criterion on which health care decisions should be made. In that perspective, it is important to provide data showing that outcome differences between elderly and nonelderly patients are partly related to decisions to forgo LSTs.

The Durban World Congress Ethics Round Table Conference Report: III. Withdrawing Mechanical ventilation--the approach should be individualized.

PURPOSE: The purpose of this study is to determine the approaches used in withdrawing mechanical ventilator support. MATERIALS AND METHODS: Speakers from the invited faculty of the World Federation of Societies of Intensive and Critical Care Medicine Congress in 2013 with an interest in ethics were asked to provide a detailed description of individual approaches to the process of withdrawal of mechanical ventilation. RESULTS: Twenty-one participants originating from 13 countries, responded to the questionnaire. Four respondents indicated that they do not practice withdrawal of mechanical ventilation, and another 4 indicated that their approach is highly variable depending on the clinical scenario. Immediate withdrawal of ventilation was practiced by a large number of the respondents (7/16; 44%). A terminal wean was practiced by just more than a third of the respondents (6/16; 38%). Extubation was practiced in more than 70% of instances among most of the respondents (9/17; 53%). Two of the respondents (2/17; 12%) indicated that they would extubate all patients, whereas 14 respondents indicated that they would not extubate all their patients. The emphasis was on tailoring the approach used to suit individual case scenarios. CONCLUSIONS: Withdrawing of ventilator support is not universal. However, even when withdrawing mechanical ventilation is acceptable, the approach to achieve this end point is highly variable and individualized.

The Durban World Congress Ethics Round Table Conference Report: I. Differences between withholding and withdrawing life-sustaining treatments.

INTRODUCTION: Withholding life-sustaining treatments (WHLST) and withdrawing life-sustaining treatments (WDLST) occur in most intensive care units (ICUs) around the world to varying degrees. METHODS: Speakers from invited faculty of the World Federation of Societies of Intensive and Critical Care Medicine Congress in 2013 with an interest in ethics were approached to participate in an ethics round table. Participants were asked if they agreed with the statement "There is no moral difference between withholding and withdrawing a mechanical ventilator." Differences between WHLST and WDLST were discussed. Official statements relating to WHLST and WDLST from intensive care societies, professional bodies, and government statements were sourced, documented, and compared. RESULTS: Sixteen respondents stated that there was no moral difference between withholding or withdrawing a mechanical ventilator, 2 were neutral, and 4 stated that there was a difference. Most ethicists and medical organizations state that there is no moral difference between WHLST and WDLST. A review of guidelines noted that all but 1 of 29 considered WHLST and WDLST as ethically or legally equivalent. CONCLUSIONS: Most respondents, practicing intensivists, stated that there is no difference between WHLST and WDLST, supporting most ethicists and professional organizations. A minority of physicians still do not accept their equivalency.

Antibiotic prescription practices and their relationship to outcome in South Africa: findings of the prevalence of infection in South African intensive care units (PISA) study.

BACKGROUND: The emergence of multidrug-resistant, extensively resistant and pan-resistant pathogens and the widespread inappropriate use of antibiotics is a global catastrophe receiving increasing attention by health care authorities. The antibiotic prescription practices in public and private intensive care units (ICUs) in South Africa are unknown. OBJECTIVE: To document antibiotic prescription practices in public and private ICUs in South Africa and to determine their relationship to patient outcomes. METHODS: A national database of public and private ICUs in South Africa was prospectively studied using a proportional probability sampling technique. RESULTS: Two hundred and forty-eight patients were recruited. Therapeutic antibiotics were initiated in 182 (73.5%), and 54.9% received an inappropriate antibiotic initially. De-escalation was practised in 33.3% and 19.7% of the public and private sector patients, respectively. Antibiotic duration was inappropriate in most cases. An appropriate choice of antibiotic was associated with an 11% mortality, while an inappropriate choice was associated with a 27% mortality (p=0.01). The mortality associated with appropriate or inappropriate duration of antibiotics was 17.6% and 20.6%, respectively (p=0.42). CONCLUSION: Inappropriate antibiotic prescription practices in ICUs in the public and private sectors in South Africa are common and are also associated with poor patient outcomes.

Evaluation of standard and modified severity of illness scores in the obstetric patient.

PURPOSE: To test discrimination and calibration of APACHE-II and SAPS-II risk prediction scores in a cohort of obstetric patients, and to evaluate the effect of modifying these scores for the physiological changes in pregnancy. MATERIALS AND METHODS: A retrospective review of obstetric patients, 12 weeks gestation to 48 hours postpartum, admitted to the ICU for more than 24 hours. APACHE-II and SAPS-II, and versions modified for the physiological changes of pregnancy, were evaluated by receiver operating characteristic (ROC) curves and standardized mortality ratios (SMR). Multivariable analysis identified other parameters associated with mortality. RESULTS: Data were obtained from 332 patients from 5 countries, with a mortality rate of 12%. Mean (± SD) APACHE-II score was 16.8 ± 6.1 and SAPS-II score 26.5 ± 15.8. Good discrimination was demonstrated with area under the ROC curves of 0.82 and 0.78 respectively, with no improvement after modification for altered maternal physiology. APACHE-II overestimated mortality, with an SMR of 0.43 (0.52 after including diagnostic weighting) compared with 0.89 for SAPS-II. Bilirubin, albumin and Glasgow Coma Scale were independently associated with mortality. CONCLUSION: APACHE-II and SAPS-II are good discriminators of illness severity and may be valuable for comparing obstetric cohorts, but APACHE-II significantly over-estimates mortality.

Infection in obstetric critical care.

Infections in critically ill obstetric patients are observed worldwide, although the incidence, aetiology and patient outcome vary between geographic locations. This chapter focuses on sepsis, with emphasis on the pathophysiology, outcome and specific management issues.