Infectious complications during therapy of acute leukaemia in Saudi Arabia

In 40 febrile neutropenic episodes during the induction and consolidation chemotherapy of acute leukaemia in Riyadh, 51% of organisms causing septicaemia were gram-negative, 26% gram-positive, 8% anaerobes and 15% fungi. In 21 (52%) febrile episodes there were pulmonary infiltrates; of the 12 where aetiology was known, six were due to fungi. Pulmonary infiltrates progressed to adult respiratory distress syndrome and death in nine instances. There was no significant occurrence of parasitic and tropical infections. The results show that the pattern of infections, during therapy of acute leukaemia in developing countries, may have important differences when compared with western centres. Empiric amphotericin B may need to be introduced at an earlier stage in patients with persistent fever or progressive pulmonary infiltrates.

Continuous infusion of ticarcillin-clavulanate for home treatment of serious infections : clinical efficacy, safety, pharmacokinetics and pharmacodynamics

Continuous infusion (CI) ticarcillin–clavulanate is a potential therapeutic improvement over conventional intermittent dosing because the major pharmacodynamic (PD) predictor of efficacy of β-lactams is the time that free drug levels exceed the MIC. This study incorporated a 6-year retrospective arm evaluating efficacy and safety of CI ticarcillin–clavulanate in the home treatment of serious infections and a prospective arm additionally evaluating pharmacokinetics (PK) and PD. In the prospective arm, steady-state serum ticarcillin and clavulanate levels and MIC testing of significant pathogens were performed. One hundred and twelve patients (median age, 56 years) were treated with a CI dose of 9.3–12.4 g/day and mean CI duration of 18.0 days. Infections treated included osteomyelitis (50 patients), septic arthritis (6), cellulitis (17), pulmonary infections (12), febrile neutropenia (7), vascular infections (7), intra-abdominal infections (2), and Gram-negative endocarditis (2); 91/112 (81%) of patients were cured, 14 (13%) had partial response and 7 (6%) failed therapy. Nine patients had PICC line complications and five patients had drug adverse events. Eighteen patients had prospective PK/PD assessment although only four patients had sufficient data for a full PK/PD evaluation (both serum steady-state drug levels and ticarcillin and clavulanate MICs from a bacteriological isolate), as this was difficult to obtain in home-based patients, particularly as serum clavulanate levels were found to deteriorate rapidly on storage. Three of four patients with matched PK/PD assessment had free drug levels exceeding the MIC of the pathogen. Home CI of ticarcillin–clavulanate is a safe, effective, convenient and practical therapy and is a therapeutic advance over traditional intermittent dosing when used in the home setting.

Complications of perioperative warfarin therapy in total knee arthroplasty

Patients presenting for knee replacement on warfarin for medical reasons often require higher levels of anticoagulation peri-operatively than primary thromboprophylaxis and may require bridging therapy with heparin. We performed a retrospective case control study on 149 consecutive primary knee arthroplasty patients to investigate whether anti-coagulation affected short-term outcomes. Specific outcome measures indicated significant increases in prolonged wound drainage (26.8% of cases vs 7.3% of controls, p<0.001); superficial infection (16.8% vs 3.3%, p<0.001); deep infection (6.0% vs 0%, p<0.001); return-to-theatre for washout (4.7% vs 0.7%, p=0.004); and revision (4.7% vs 0.3%, p=0.001). Management of patients on long-term warfarin therapy following TKR is particularly challenging, as the surgeon must balance risk of thromboembolism against post-operative complications on an individual patient basis in order to optimise outcomes.

Evaluation of the cost-effectiveness of strategies claiming to reduce the risk of surgical site infections following primary total hip arthroplasty

Background Total hip arthroplasty (THA) is a commonly performed procedure and numbers are increasing with ageing populations. One of the most serious complications in THA are surgical site infections (SSIs), caused by pathogens entering the wound during the procedure. SSIs are associated with a substantial burden for health services, increased mortality and reduced functional outcomes in patients. Numerous approaches to preventing these infections exist but there is no gold standard in practice and the cost-effectiveness of alternate strategies is largely unknown. Objectives The aim of this project was to evaluate the cost-effectiveness of strategies claiming to reduce deep surgical site infections following total hip arthroplasty in Australia. The objectives were: 1. Identification of competing strategies or combinations of strategies that are clinically relevant to the control of SSI related to hip arthroplasty 2. Evidence synthesis and pooling of results to assess the volume and quality of evidence claiming to reduce the risk of SSI following total hip arthroplasty 3. Construction of an economic decision model incorporating cost and health outcomes for each of the identified strategies 4. Quantification of the effect of uncertainty in the model 5. Assessment of the value of perfect information among model parameters to inform future data collection Methods The literature relating to SSI in THA was reviewed, in particular to establish definitions of these concepts, understand mechanisms of aetiology and microbiology, risk factors, diagnosis and consequences as well as to give an overview of existing infection prevention measures. Published economic evaluations on this topic were also reviewed and limitations for Australian decision-makers identified. A Markov state-transition model was developed for the Australian context and subsequently validated by clinicians. The model was designed to capture key events related to deep SSI occurring within the first 12 months following primary THA. Relevant infection prevention measures were selected by reviewing clinical guideline recommendations combined with expert elicitation. Strategies selected for evaluation were the routine use of pre-operative antibiotic prophylaxis (AP) versus no use of antibiotic prophylaxis (No AP) or in combination with antibiotic-impregnated cement (AP & ABC) or laminar air operating rooms (AP & LOR). The best available evidence for clinical effect size and utility parameters was harvested from the medical literature using reproducible methods. Queensland hospital data were extracted to inform patients’ transitions between model health states and related costs captured in assigned treatment codes. Costs related to infection prevention were derived from reliable hospital records and expert opinion. Uncertainty of model input parameters was explored in probabilistic sensitivity analyses and scenario analyses and the value of perfect information was estimated. Results The cost-effectiveness analysis was performed from a health services perspective using a hypothetical cohort of 30,000 THA patients aged 65 years. The baseline rate of deep SSI was 0.96% within one year of a primary THA. The routine use of antibiotic prophylaxis (AP) was highly cost-effective and resulted in cost savings of over $1.6m whilst generating an extra 163 QALYs (without consideration of uncertainty). Deterministic and probabilistic analysis (considering uncertainty) identified antibiotic prophylaxis combined with antibiotic-impregnated cement (AP & ABC) to be the most cost-effective strategy. Using AP & ABC generated the highest net monetary benefit (NMB) and an incremental $3.1m NMB compared to only using antibiotic prophylaxis. There was a very low error probability that this strategy might not have the largest NMB (<5%). Not using antibiotic prophylaxis (No AP) or using both antibiotic prophylaxis combined with laminar air operating rooms (AP & LOR) resulted in worse health outcomes and higher costs. Sensitivity analyses showed that the model was sensitive to the initial cohort starting age and the additional costs of ABC but the best strategy did not change, even for extreme values. The cost-effectiveness improved for a higher proportion of cemented primary THAs and higher baseline rates of deep SSI. The value of perfect information indicated that no additional research is required to support the model conclusions. Conclusions Preventing deep SSI with antibiotic prophylaxis and antibiotic-impregnated cement has shown to improve health outcomes among hospitalised patients, save lives and enhance resource allocation. By implementing a more beneficial infection control strategy, scarce health care resources can be used more efficiently to the benefit of all members of society. The results of this project provide Australian policy makers with key information about how to efficiently manage risks of infection in THA.

In Response: "Oral versus IV treatment for catheter-related bloodstream infections - by Burke A. Cunha"

In his letter Cunha suggests that oral antibiotic therapy is safer and less expensive than intravenous therapy via central venous catheters (CVCs) (1). The implication is that costs will fall and increased health benefits will be enjoyed resulting in a gain in efficiency within the healthcare system. CVCs are often used in critically ill patients to deliver antimicrobial therapy, but expose patients to a risk of catheter-related bloodstream infection (CRBSI). Our current knowledge about the efficiency (i.e. costeffectiveness) of allocating resources toward interventions that prevent CRBSI in patients requiring a CVC has already been reviewed (2). If for some patient groups antimicrobial therapy can be delivered orally, instead of through a CVC, then the costs and benefits of this alternate strategy should be evaluated...

An economic case for providing free access to antiretroviral therapy for HIV-positive people in South Australia

Background As financial constraints can be a barrier to accessing HIV antiretroviral therapy (ART), we argue for the removal of copayment requirements from HIV medications in South Australia. Methods Using a simple mathematical model informed by available behavioural and biological data and reflecting the HIV epidemiology in South Australia, we calculated the expected number of new HIV transmissions caused by persons who are not currently on ART compared with transmissions for people on ART. The extra financial investment required to cover the copayments to prevent an HIV infection was compared with the treatment costs saved due to averting HIV infections. Results It was estimated that one HIV infection is prevented per year for every 31.4 persons (median, 24.0–42.7 interquartile range (IQR)) who receive treatment. By considering the incremental change in costs and outcomes of a change in program from the current status quo, it would cost the health sector $17 860 per infection averted (median, $13 651–24 287 IQR) if ART is provided as a three-dose, three-drug combination without requirements for user-pay copayments. Conclusions The costs of removing copayment fees for ART are less than the costs of treating extra HIV infections that would result under current conditions. Removing the copayment requirement for HIV medication would be cost-effective from a governmental perspective.

How different are complications that affect the older adult inpatient?

Objective: The incidence and cost of complications occurring in older and younger inpatients were compared. Design: Secondary analysis of hospital-recorded diagnosis and costs for multiday-stay inpatients in 68 public hospitals in two Australian states. Main outcome measures: A complication is defined as a hospital-acquired diagnosis that required additional treatment. The Australian Classification of Hospital-Acquired Diagnoses system is used to identify these complications. Results: Inpatients aged >70 years have a 10.9% complication rate, which is not substantially different from the 10.89% complication rate found in patients aged <70 years. Examination of the probability by single years, however, showed that the peak incidence associated with the neonatal period and childbirth is balanced by rates of up to 20% in patients >80 years. Examining the adult patient population (40–70 years), we found that while some common complications are not age specific (electrolyte disorders and cardiac arrhythmias), others (urinary tract and lower respiratory tract infections) are more common in the older adult inpatient. Conclusion: For inpatients aged >70 years, the risks of complications increase. The incidence of hospital-acquired diagnoses in older adults differs significantly from incidence rates found in younger cohorts. Urinary tract infection and alteration to mental state are more common in older adult inpatients. Surprisingly, these complexities do not result in additional costs when compared with costs for the same complications in younger adults. Greater awareness of these differing patterns will allow patient safety efforts for older patients to focus on complications with the highest incidence and cost.

Educational interventions for preventing vascular catheter bloodstream infections in critical care: Evidence map, systematic review and economic evaluation

Background Bloodstream infections resulting from intravascular catheters (catheter-BSI) in critical care increase patients' length of stay, morbidity and mortality, and the management of these infections and their complications has been estimated to cost the NHS annually £19.1–36.2M. Catheter-BSI are thought to be largely preventable using educational interventions, but guidance as to which types of intervention might be most clinically effective is lacking. Objective To assess the effectiveness and cost-effectiveness of educational interventions for preventing catheter-BSI in critical care units in England. Data sources Sixteen electronic bibliographic databases – including MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, Cumulative Index to Nursing and Allied Health Literature (CINAHL), NHS Economic Evaluation Database (NHS EED), EMBASE and The Cochrane Library databases – were searched from database inception to February 2011, with searches updated in March 2012. Bibliographies of systematic reviews and related papers were screened and experts contacted to identify any additional references. Review methods References were screened independently by two reviewers using a priori selection criteria. A descriptive map was created to summarise the characteristics of relevant studies. Further selection criteria developed in consultation with the project Advisory Group were used to prioritise a subset of studies relevant to NHS practice and policy for systematic review. A decision-analytic economic model was developed to investigate the cost-effectiveness of educational interventions for preventing catheter-BSI. Results Seventy-four studies were included in the descriptive map, of which 24 were prioritised for systematic review. Studies have predominantly been conducted in the USA, using single-cohort before-and-after study designs. Diverse types of educational intervention appear effective at reducing the incidence density of catheter-BSI (risk ratios statistically significantly < 1.0), but single lectures were not effective. The economic model showed that implementing an educational intervention in critical care units in England would be cost-effective and potentially cost-saving, with incremental cost-effectiveness ratios under worst-case sensitivity analyses of < £5000/quality-adjusted life-year. Limitations Low-quality primary studies cannot definitively prove that the planned interventions were responsible for observed changes in catheter-BSI incidence. Poor reporting gave unclear estimates of risk of bias. Some model parameters were sourced from other locations owing to a lack of UK data. Conclusions Our results suggest that it would be cost-effective and may be cost-saving for the NHS to implement educational interventions in critical care units. However, more robust primary studies are needed to exclude the possible influence of secular trends on observed reductions in catheter-BSI.

How many inpatients in our hospitals have foot complications? The foot disease in inpatients study

Background Foot complications have been found to affect large proportions of hospital in patients with diabetes. However, no studies have investigated the proportion of foot complications affecting all people in general inpatient populations. The aims of this cross-sectional study were to investigate the point-prevalence of different foot complications in general inpatient populations, analyse differences in diabetes and non-diabetes sub-groups, and examine characteristics of people primarily admitted for a foot complication. Methods Eligible participants were all adults admitted overnight, for any reason, into five diverse hospitals on one day; excluding maternity, mental health and cognitively impaired patients. All participants underwent a physical foot examination, by trained podiatrists using validated measures, to clinically diagnose different foot complications; including foot wounds, infections, deformity, peripheral arterial disease (PAD) and peripheral neuropathy (PN). Data were also collected on participants' primary reason for admission and a range of demographic, social determinant, medical history, foot complication history, self-care and footwear risk factors. Results Overall, 733 participants consented (83% of eligible participants); mean(±SD) age 62(±19) years, 480 (55.8%) male and 172 (23.5%) had diabetes. Foot complication prevalence included: wounds 9.0% (95% CI) (5.1-8.7), infections 3.3% (2.2-4.9), deformity 22.4% (19.5-26.7), PAD 21.0% (18.2-24.1) and PN 22.0% (19.1-25.1). Diabetes populations had significantly more foot complications than non-diabetes (p < 0.01); wounds (15.7% vs 7.0%), infections (7.1% vs 2.2%), deformity (30.5% vs 19.9%), PAD (35.1% vs 16.7%) and PN (43.3% vs 15.4%). Foot complications were the primary reason for admission in 7.4% (95% CI) (5.7-9.5) of all participants. In a backwards stepwise multivariate analysis having a foot complication as the primary reason for admission was independently associated (OR (95% CI) with foot wounds (18.9 (7.3-48.7)), foot infections (6.0 (1.6-22.4)), history of amputation (4.7 (1.3-17.0) and PAD (2.9 (1.3-6.6)). Conclusions Findings of this study indicate one in every ten hospital inpatients had an active foot wound or infection. In patients with diabetes had significantly higher proportions of foot complications than non-diabetes inpatients. Remarkably one in every thirteen inpatients in this study were primarily hospitalised for a foot complication. Further research and policy is required to tackle this seemingly large inpatient foot complication burden.

Geographic Variation of Notified Ross River Virus Infections in Queensland, Australia, 1985-1996

The spatial and temporal variations of Ross River virus infections reported in Queensland, Australia, between 1985 and 1996 were studied by using the Geographic Information System. The notified cases of Ross River virus infection came from 489 localities between 1985 and 1988, 805 between 1989 and 1992, and 1,157 between 1993 and 1996 (chi2(df = 2) = 680.9; P < 0.001). There was a marked increase in the number of localities where the cases were reported by 65 percent for the period of 1989-1992 and 137 percent for 1993-1996, compared with that for 1985-1988. The geographic distribution of the notified Ross River virus cases has expanded in Queensland over recent years. As Ross River virus disease has impacted considerably on tourism and industry, as well as on residents of affected areas, more research is required to explore the causes of the geographic expansion of the notified Ross River virus infections.