Evaluating the cost-effectiveness of strategies to prevent vascular access device infections.

The evidence clearly indicates that a care-bundle approach is needed to prevent catheter-related bloodstream infections (CRBSIs). Such an approach includes the need for education, training and adequate staffing, sterile barrier precautions, skin preparation, use of intravenous dressings and antimicrobial prophylaxis. Care bundles advise which aspects must be given priority and what procedures will produce optimum outcomes. All of these activities come at a cost, yet very few studies have investigated the extent to which they are cost-effective. As a result, it is difficult to make evidence-based decisions on the potential cost savings that may be achieved with a care-bundle approach. This article describes the existing health-economic evidence on strategies to prevent CRBSIs and outlines the criteria for future research.

European perspective and update on the management of nosocomial pneumonia due to methicillin-resistant Staphylococcus aureus after more than 10 years of experience with linezolid.

Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of antimicrobial-resistant hospital-acquired infections worldwide and remains a public health priority in Europe. Nosocomial pneumonia (NP) involving MRSA often affects patients in intensive care units with substantial morbidity, mortality and associated costs. A guideline-based approach to empirical treatment with an antibacterial agent active against MRSA can improve the outcome of patients with MRSA NP, including those with ventilator-associated pneumonia. New methods may allow more rapid or sensitive diagnosis of NP or microbiological confirmation in patients with MRSA NP, allowing early de-escalation of treatment once the pathogen is known. In Europe, available antibacterial agents for the treatment of MRSA NP include the glycopeptides (vancomycin and teicoplanin) and linezolid (available as an intravenous or oral treatment). Vancomycin has remained a standard of care in many European hospitals; however, there is evidence that it may be a suboptimal therapeutic option in critically ill patients with NP because of concerns about its limited intrapulmonary penetration, increased nephrotoxicity with higher doses, as well as the emergence of resistant strains that may result in increased clinical failure. Linezolid has demonstrated high penetration into the epithelial lining fluid of patients with ventilator-associated pneumonia and shown statistically superior clinical efficacy versus vancomycin in the treatment of MRSA NP in a phase IV, randomized, controlled study. This review focuses on the disease burden and clinical management of MRSA NP, and the use of linezolid after more than 10 years of clinical experience.

Guidelines for the management of hospital-acquired pneumonia in the UK: report of the working party on hospital-acquired pneumonia of the British Society for Antimicrobial Chemotherapy.

These evidence-based guidelines have been produced after a systematic literature review of a range of issues involving prevention, diagnosis and treatment of hospital-acquired pneumonia (HAP). Prevention is structured into sections addressing general issues, equipment, patient procedures and the environment, whereas in treatment, the structure addresses the use of antimicrobials in prevention and treatment, adjunctive therapies and the application of clinical protocols. The sections dealing with diagnosis are presented against the clinical, radiological and microbiological diagnosis of HAP. Recommendations are also made upon the role of invasive sampling and quantitative microbiology of respiratory secretions in directing antibiotic therapy in HAP/ventilator-associated pneumonia.

Indicators of bacterial infection in patients with acute exacerbation of chronic bronchitis for application in clinical trials of antibacterial drugs.

OBJECTIVES: This study examined the accuracy of: (a) patient symptoms; (b) microscopic examination of sputum purulence (>25 WBCs and <10 epithelial cells) and (c) microscopic examination of morphological bacterial cell types, in identifying bacterial infection in patients with an acute exacerbation of chronic bronchitis (AECB) for entry to clinical trials. METHODS: Subjects had a worsening of at least two symptoms from: dyspnoea, sputum volume, and sputum purulence (Anthonisen Type 1 or 2 exacerbation). Sputum samples were collected from all subjects. RESULTS: A total of 97 sputum samples were evaluated. Overall, 58 (60%) subjects were culture-positive; 22 of 29 (76%) subjects with Type 2 exacerbation had a bacterial pathogen isolated compared with 36 of 68 (53%) Type 1 subjects. This difference was not statistically significant. Microscopically purulent samples were found to be significantly more likely to be culture-positive than non-purulent samples. However, the sensitivity (60%) and specificity (67%); and the positive predictive value (73%) and negative predictive value (53%) observed, means that this is not an ideal predictive test for clinical trials. A semi-quantitative approach to Gram staining was identified as a potential indicator of bacterial infection. Sputum specimens with one bacterial cell type present at >10 cells per field, or more than one cell type present with at least one type at a concentration of >25 cells per field, had a high proportion (91%) of culture-positive specimens. CONCLUSIONS: Symptoms alone are a poor indicator of bacterial infection. A semi-quantitative examination of a Gram-stained sputum preparation was the best indicator of bacterial infection. This finding may have relevance in the design of clinical trials of antibacterial drugs in AECB.

Investigation into the selection frequency of resistant mutants and the bacterial kill rate by levofloxacin and ciprofloxacin in non-mucoid Pseudomonas aeruginosa isolates from cystic fibrosis patients.

The frequency by which resistant Pseudomonas aeruginosa strains could be selected was compared for two antibiotics, levofloxacin and ciprofloxacin. Seven distinct strains were cultured on plates containing 1x, 2x, 4x and 8x the minimum inhibitory concentration (MIC) of the antibiotic under investigation. Resistant mutants were more readily isolated by growth on culture plates that contained ciprofloxacin, and the resulting MIC of the resistant mutant was also more frequently increased. Time-kill studies on comparable strains where the MIC for both antibiotics had increased by at least fourfold showed no difference between the two agents.

Randomized, double-blind study comparing 5- and 7-day regimens of oral levofloxacin in patients with acute exacerbation of chronic bronchitis.

A randomized, double-blind, multicentre study was conducted in adult patients with acute exacerbation of chronic bronchitis (AECB), to compare the efficacy of a 5-day course of levofloxacin 500 mg once daily, with the standard 7-day regimen at the same dose. Five hundred and thirty-two patients from 48 centres in 10 countries were randomized to receive levofloxacin: 268 and 264 received the 5- and 7-day courses, respectively. The primary efficacy analysis was the clinical response at 7-10 days post-treatment in the per-protocol (PP) population. Clinical success rates in the primary PP analysis of 482 patients were 82.8% (197/238) for the 5-day group and 84.8% (207/244) for the 7-day group. The difference in success rates was -2.1% with a 95% CI of (-9.1 to 4.9%). The bacteriological response showed eradication rates of 82.1% (92/112) and 83.2% (84/101) in the 5- and 7-day groups, respectively. Both treatments were well tolerated. These results show that for patients with AECB levofloxacin 500 mg once daily for 5 days provides equivalent clinical and bacteriological success to the same dose given for 7 days irrespective of the patient's age, the frequency of exacerbations or the presence of co-existing cardiopulmonary or chronic obstructive airways disease.

Surveillance studies: how can they help the management of infection?

The increase in antimicrobial resistance has led to predictions of doom in the international press and to depression in the medical community. It has focused attention upon measures for fighting resistance, foremost of which is susceptibility surveillance. Until recently, global efforts at surveillance have been largely uncoordinated and random. This scene is rapidly changing with the World Health Organization (WHO), among others, leading multidisciplinary, targeted initiatives. In terms of individual surveillance programmes, much has been learned about their design. The best of these, the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC), SENTRY and the Alexander Project, involve well-defined patient and organism groups against key denominators, and use standardized, internationally recognized methods that are quality-controlled, explore susceptibility quantitatively and include investigation of resistance mechanisms. Results are rapidly returned to the user. Evidence shows that surveillance, when used to guide policies on antibiotic use and infection control, can be helpful in the fight to control the development and spread of resistance. Further work is required to demonstrate these benefits and quantify them fully.

Worthwhile infection control information? A report from the 38th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), San Diego, California: 24-27 September 1998.

A review is presented of some of the presentations delivered at ICAAC 1998. These cover the subjects of handwashing, occupational infections risk exposure for healthcare workers and alterations in catheter practice to reduce both intra-venous and urinary infections.

The effect of specimen processing delay on borate urine preservation.

AIM: To investigate the effect on urine culture results and their clinical interpretation of delaying the processing of urine samples in which boric acid had been used as a preservative. METHODS: 792 mid-stream specimens of urine from patients attending their general practitioner were received in borate containing plastic jars. The specimens were cultured upon receipt, stored at room temperature, and then recultured the following morning. RESULTS: After overnight delayed culture, the results were altered in 16% of samples and the clinical interpretation of these findings differed in 8% of specimens. In 28 samples (3.5%) the bacterium isolated on initial culture was not the same as that obtained by culture after overnight storage. CONCLUSIONS: Boric acid urine preservation used for overnight delayed processing of samples is associated with a significant alteration in culture results and the attendant clinical interpretation of such specimens. Rapid transportation/processing of urine specimens must remain the optimum procedure.

Investigation of infection in the neutropenic patient with fever.

Episodes of infection occurring in neutropenic patients are often associated with high levels of morbidity and mortality and prompt, accurate diagnosis allowing the rapid instigation of appropriate treatment can lead to an improved outcome. Recent developments in laboratory technology have increased the range of investigations available to the physician. The improved sensitivity of traditional microbiological culture, methods for antigen and antibody detection and the advances in molecular biology are among the reasons for an increased ability to detect both familiar and novel pathogens. This article describes the current methods available for determining the aetiology of an infectious episode in these patients. A plan of management for investigation of febrile episodes in neutropenic patients is suggested.