From evidence-based guideline methodology to quality of care standards.
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Evidence-Based Medicine↗
Biomedical subjects
Dilip Nathwani
Publications and source records attributed to Dilip Nathwani.
Case report: isolation of a European bat lyssavirus type 2a from a fatal human case of rabies encephalitis.
A 55-year-old bat conservationist was admitted to Ninewells Hospital, Dundee, Scotland, on November 11, 2002, with an acute haematemesis. He gave a 5-day history of pain and paraesthesia in the left arm, followed by increasing weakness of his limbs with evidence of an evolving encephalitis with cerebellar involvement. The patient had never been vaccinated against rabies and did not receive postexposure treatment. Using a hemi-nested reverse transcriptase-polymerase chain reaction (RT-PCR), saliva samples taken intravitam from different dates proved positive for rabies. A 400-bp region of the nucleoprotein gene was sequenced for confirmation and identified a strain of European bat lyssavirus (EBLV) type 2a. The diagnosis was confirmed using the fluorescent antibody test (FAT) and by RT-PCR on three brain samples (cerebellum, medulla, and hippocampus) taken at autopsy. In addition, a mouse inoculation test (MIT) was performed. Between 13 and 17 days postinfection, clinical signs of a rabies-like illness had developed in all five inoculated mice. Brain smears from each infected animal were positive by the FAT and viable virus was isolated. This fatal incident is only the second confirmed case of an EBLV type-2 infection in a human after exposure to bats.
Animals↗
Vancomycin for Staphylococcus aureus therapy of respiratory tract infections: the end of an era?
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Anti-Bacterial Agents↗
Evaluation of outcomes in community-acquired pneumonia: a guide for patients, physicians, and policy-makers.
Community-acquired pneumonia (CAP) is a key target for research and quality improvement in acute medicine. However, many of the outcome measures used in prognostic and antibiotic studies are not validated and do not capture features of outcome that are important to patients. Substitutes for traditional outcome measures include a recently validated patient-based symptom questionnaire (the CAP-Sym) and process-of-care measures. The interpretation of outcomes also depends on the quality of the study design and methods used. This paper discusses the advantages and disadvantages of outcome, process-of-care, and economic measures in CAP and the interpretation of these measures in randomised and observational studies. A core set of measures for use in clinical CAP research and performance measurement is proposed.
Administrative Personnel↗
Cost-minimization analysis and audit of antibiotic management of bone and joint infections with ambulatory teicoplanin, in-patient care or outpatient oral linezolid therapy.
Bone and joint infections are significant causes of morbidity, mortality and healthcare costs. The cost of treatment for such infections is driven primarily by the length of hospital stay. Many of these infections will require treatment with prolonged periods of parenteral antibiotic therapy. Clinicians and healthcare managers are being attracted increasingly by administering treatment in the ambulatory setting as this offers clinical, economic and quality of life advantages from both the hospital's and patient's perspective. Our retrospective audit of managing 55 treatment episodes of bone and joint infections with teicoplanin delivered in the outpatient or home setting revealed that the mean cost of care per episode of infection was less with treatment in the ambulatory setting ( pound 1749.15) compared with the in-patient setting ( pound 11 400) or compared with the hypothetical situation of treatment with oral linezolid in the home setting ( pound 2546). Teicoplanin therapeutic drug monitoring appears to be valuable in establishing optimal serum levels, which appear to correlate with good clinical outcomes. The potential for alternative day or thrice weekly dosing with teicoplanin may offer further cost advantages whilst maintaining equivalent clinical effectiveness.
Acetamides↗
Impact of methicillin-resistant Staphylococcus aureus infections on key health economic outcomes: does reducing the length of hospital stay matter?
The clinical and economic impact of methicillin-resistant staphylococcal infections on the patient, the hospital and the community is significant and continues to increase. Methicillin-resistant Staphylococcus aureus infections, in particular, represent a substantial burden of resistant infections in the hospital. As such, it is important to analyse the cost parameters associated with an episode of infection. Key determinants of the total cost of an episode of infection include fixed costs and hotel costs; the contribution of antimicrobial therapy, including drug acquisition and delivery costs, is comparatively marginal. Therefore, decreasing the hospital length of stay by promoting earlier hospital discharge will significantly reduce overall costs and, in effect, increase the efficiency and cost-effectiveness of the hospital. Linezolid, the first marketed agent of a new class of oxazolidinone antibiotics, is effective in the treatment of serious Gram-positive infections. Its availability in both intravenous (iv) and oral formulations (the latter of which is 100% bioavailable) facilitates early discharge from hospital. Hospitalized patients with methicillin-resistant staphylococcal infections who were treated with either linezolid or vancomycin demonstrated no significant differences in clinical outcome or mortality. However, compared with vancomycin, administration of linezolid reduced the duration of iv therapy and increased the chance of being discharged during the first week of hospitalization. These effects were most pronounced in the subset of patients with skin and soft tissue infections. Knowledge of these data may influence prescribing practices at the individual and organizational levels and, in turn, reduce the economic burden associated with MRSS infections.
Acetamides↗
Ambulatory antimicrobial use: the value of an outcomes registry.
The opportunity for treating many serious infections in the community or ambulatory setting is growing. Outpatient parenteral antimicrobial therapy (OPAT) provides many potential advantages to the patient, hospital and clinician, including quality of life, cost savings and reduced risk of hospital-acquired infections due to antibiotic-resistant organisms. However, despite the evolution of this type of care in many countries, there have been continued questions and concerns about its safety and effectiveness. As with many new forms of therapy in medicine, the value of OPAT is in doubt because of the lack of published information concerning outcomes and its impact on patient care. In order to examine the quality of such programmes, an outcome-based registry of patients has been developed for OPAT. The core outcomes measures include clinical effectiveness, eradication of bacteria and adverse antibiotic events. The registry may also be adapted for benchmarking for quality assurance, surveying performance of new antimicrobials, cost effectiveness studies and comparisons of different antibiotics and their side effects.
Ambulatory Care↗
Use of indicators to evaluate the quality of community-acquired pneumonia management.
Quality-assessment indicators for community-acquired pneumonia (CAP) founded on health care structure, process, and outcome have been recommended as a potential audit tool to evaluate the delivery of care. We prospectively audited the treatment of 205 patients admitted with CAP to 2 hospitals in Dundee against some of these key standards. Patients with severe CAP were more likely to die (mortality rate, 42% versus 7%) and to receive antibiotics by the intravenous route (relative risk [RR], 1.81; 95% confidence interval [CI], 1.38-2.37) and within 4 hours of admission to the hospital (RR, 1.22; 95% CI, 0.92-1.62). There was a lack of uniformity regarding the amount of oxygen prescribed, with evidence of poor case record and drug prescription chart documentation related to oxygen therapy. Adherence to the recommended antibiotic policy was associated with reduced risk of death or readmission to the hospital (RR, 0.58; 95% CI, 0.34-1.00). However, in a multivariate analysis, severity of pneumonia was the strongest predictor of death or readmission (P=.004), and adherence to the antibiotic policy was not statistically significant (P=.154). Our study has confirmed the value of quality indicators in evaluating our CAP management and has stimulated the development and implementation of a local hospital-based integrated care pathway.
Aged↗
Sequential antibiotic therapy.
Antimicrobials are an important source of hospital expenditure. Traditionally, severe bacterial infections have been treated initially with intravenous antibiotics, followed by physician-directed switch to oral therapy. Unfortunately this approach results in unnecessary prolongation of intravenous treatment, with all its inherent disadvantages. Sequential antibiotic therapy, however, ensures an early switch to the oral route when the patient is clinically stable. This increasingly employed strategy is safe and results in improved quality and cost-effectiveness of health care. To ensure timely and appropriate switch, such programmes need to be underpinned by clear guidelines and supported by a multidisciplinary team. In the future, key questions, such as what is the optimal time of switch for specific infections, and can conditions such as osteomyelitis and endocarditis be efficaciously treated with oral therapy, need to be answered. Only then will clinicians be able to practise evidence-based infection management incorporating sequential antimicrobial therapy.
Journal Article↗
Penicillins. A current review of their clinical pharmacology and therapeutic use.
The penicillins are a large group of bicyclic ring compounds which contain a 4-membered beta-lactam ring (penams) fused to a 5-membered thiazolidine ring. Benzylpenicillin (penicillin G) was the first natural penicillin with potent activity against all Gram-positive pathogens, Gram-negative cocci and some spirochaetes and actinomycetes. For the last 50 years benzylpenicillin has been the mainstay of therapy for serious pneumococcal, streptococcal, meningococcal and gonococcal infections. However, the past decade has seen the emergence of resistance in certain parts of the world, initially among the gonococci, and more recently among the pneumococci and meningococci. Discovery of the 6-aminopenicillinamic acid nucleus has led to considerable manipulation of the basic ring structure, resulting initially in the synthesis of ampicillin, and subsequently the other aminopenicillins, analogues, esters and prodrugs. These drugs have the advantages of improved oral bioavailability and superior activity against Haemophilus influenzae, certain Gram-negative bacilli, salmonellae, enterococci and Listeria monocytogenes, making these agents popular in the treatment of upper and lower respiratory tract infections and urinary tract infections. The increasing spread of bacterial resistance, particularly among Enterobacteriaceae and H. influenzae, has curtailed the usefulness of these drugs in these clinical settings. To counteract this problem, a number of agents combining a penicillin and a beta-lactamase inhibitor (e.g. clavulanic acid, tazobactam and sulbactam) have been developed. These inhibitors have no intrinsic antibacterial activity, but combining them with a penicillin (e.g. amoxicillin/clavulanic acid) confers greater stability to beta-lactamases and hence a broader spectrum of activity. The emergence of penicillinase-producing staphylococci that rendered benzylpenicillin ineffective also stimulated the search for penicillinase-resistant penicillins--methicillin and nafcillin, followed by the acid-stable isoxazolyl penicillins. These agents are now the principle antistaphylococcal treatment. Methicillin-resistant coagulase-negative staphylococci are currently a major cause of hospital sepsis, and are resistant to these latter agents. Enteric Gram-negative bacilli have been the predominant cause of serious hospital infections during the last 30 years. Further manipulation of the penicillin structure has resulted in compounds with broader activity against Gram-negative bacilli, particularly Pseudomonas aeruginosa, while retaining activity against Gram-positive pathogens. The carboxypenicillins were the first step in this direction, but have been largely superseded by the ureidopenicillins. These agents have better activity against P. aeruginosa, and are still effective against Gram-negative and Gram-positive bacteria, including enterococci and anaerobic organisms.(ABSTRACT TRUNCATED AT 400 WORDS)
Bacterial Infections↗