A randomised trial of home vs hospital intravenous antibiotic therapy in adults with infectious diseases

Objective. Despite widespread adoption of home care services, few randomised trials have compared health outcomes in the hospital and at home. We report a prospective, randomised trial of home versus hospital therapy in adults receiving intravenous (IV) antibiotics. Our objective was to show that home care is a feasible alternative to hospitalisation over a broad range of infections, without compromise to quality of life (QOL) or clinical outcomes. Methods. Consenting adults requiring IV antibiotics were randomised to complete therapy at home or in hospital. Short Form 36 and Perceived Health Competence Scale (PHCS) were used for assessment of QOL. Statistical analysis used unpaired t-tests, Mann-Whitney tests and ANOVA. Results. One hundred and twenty-nine admissions were referred. Recruitment was hampered by patient preference for one therapy over another. 82 (62%) were included and randomised: 44 to home, 38 to hospital; the two groups had comparable characteristics. There were no differences in improvements in QOL and PHCS scores between the two groups after treatment. Treatment duration was median 11.5 days (range 3 - 57) and 11 days (range 4 - 126) for home and hospital groups, respectively. Home therapy costs, approximately, half that of hospital therapy. Time to readmission was longer after hospital therapy. Conclusion. Out study showed that home IV therapy is welt tolerated, is less costly, is not associated with any major disadvantage to QOL or clinical outcomes compared to hospital therapy, and is an appropriate treatment option for selected patients. (C) 2003 The British Infection Society. Published by Elsevier Ltd. All rights reserved.

Antibiotic therapy for Klebsiella pneumoniae bacteremia: Implications of production of extended-spectrum beta-lactamases

The prevalence of extended-spectrum beta-lactamase (ESBL) production by Klebsiella pneumonia approaches 50% in some countries, with particularly high rates in eastern Europe and Latin America. No randomized trials have ever been performed on treatment of bacteremia due to ESBL-producing organisms; existing data comes only from retrospective, single-institution studies. In a prospective study of 455 consecutive episodes of Klebsiella pneumoniae bacteremia in 12 hospitals in 7 countries, 85 episodes were due to an ESBL-producing organism. Failure to use an antibiotic active against ESBL-producing K. pneumoniae was associated with extremely high mortality. Use of a carbapenem ( primarily imipenem) was associated with a significantly lower 14-day mortality than was use of other antibiotics active in vitro. Multivariate analysis including other predictors of mortality showed that use of a carbapenem during the 5-day period after onset of bacteremia due to an ESBL-producing organism was independently associated with lower mortality. Antibiotic choice is particularly important in seriously ill patients with infections due to ESBL-producing K. pneumoniae.

Empiric management of community-acquired pneumonia in Australian emergency departments

Objective: To describe empiric community-acquired pneumonia (CAP) management in Australian hospital emergency departments (EDs) and evaluate this against national guidelines, including use of the pneumonia severity index and antibiotic selection. Design: A multicentre, cross-sectional, retrospective audit, April 2003 to February 2005. Setting: 37 Australian hospitals: 22 principal referral hospitals, six large major city hospitals, four large regional hospitals, four medium hospitals and one private hospital. Participants: Adult patients with a diagnosis of CAP made in the ED. Data on 20 consecutive CAP ED presentations were collected in participating hospitals. Outcome measures: Documented use of the pneumonia severity index, initial antibiotic therapy prescribed in the ED, average length of stay, inpatient mortality, and concordance with national guidelines. Results: 691 CAP presentations were included. Pneumonia severity index use was documented in 5% of cases. Antibiotic therapy covering common bacterial causes of CAP was prescribed in 67% of presentations, although overall concordance with national guidelines was 18%. Antibiotic prescribing was discordant due to inadequate empiric antimicrobial cover, allergy status (including contraindication to penicillin), inappropriate route of administration and/or inappropriate antibiotic choice according to recommendations. There was no significant difference between concordant and discordant antibiotic prescribing episodes in average length of stay (5.0 v 5.7 days; P=0.22) or inpatient mortality (1.6% v 4.1%; chi(2) = 1.82; P=0.18). Conclusions: Antibiotic therapy for CAP prescribed in Australian EDs varied. Concordance with national CAP guidelines was generally low. Targeted interventions are required to improve concordance.

Disease risk and mortality prediction in intensive care patients with pneumonia. Australian and New Zealand practice in intensive care (ANZPIC II)

This study of ventilated patients investigated pneumonia risk factors and outcome predictors in 476 episodes of pneumonia (48% community-acquired pneumonia, 24% hospital-acquired pneumonia, 28% ventilator-associated pneumonia) using a prospective survey in 14 intensive care units within Australia and New Zealand. For community acquired pneumonia, mortality increased with immunosuppression (OR 5.32, CI 95% 1.58-17.99, P < 0. 01), clinical signs of consolidation (OR 2.43, CI 95% 1.09-5.44, P = 0. 03) and Sepsis-Related Organ Failure Assessment (SOFA) scores (OR 1.19, CI 95% 1.08-1.30, P < 0. 001) but improved if appropriate antibiotic changes were made within three days of intensive care unit admission (OR 0.42, CI 95% 0.20-0.86, P = 0.02). For hospital-acquired pneumonia, immunosuppression (OR 6.98, CI 95% 1.16-42.2, P = 0.03) and non-metastatic cancer (OR 3.78, CI 95% 1.20-11.93, P = 0.02) were the principal mortality predictors. Alcoholism (OR 7.80, CI 95% 1.20-1750, P < 0.001), high SOFA scores (OR 1.44, CI 95% 1.20-1.75, P = 0.001) and the isolation of high risk organisms including Pseudomonas aeruginosa, Acinetobacter spp, Stenotrophomonas spp and methicillin resistant Staphylococcus aureus (OR 4.79, CI 95% 1.43-16.03, P = 0.01), were associated with increased mortality in ventilator-associated pneumonia. The use of non-invasive ventilation was independently protective against mortality for patients with community-acquired and hospital-acquired pneumonia (OR 0.35, CI 95% 0.18-0.68, P = 0.002). Mortality was similar for patients requiting both invasive and non-invasive ventilation and non-invasive ventilation alone (21% compared with 20% respectively, P = 0.56). Pneumonia risks and mortality predictors in Australian and New Zealand ICUs vary with pneumonia type. A history of alcoholism is a major risk factor for mortality in ventilator-associated pneumonia, greater in magnitude than the mortality effect of immunosuppression in hospital-acquired pneumonia or community-acquired pneumonia. Non-invasive ventilation is associated with reduced ICU mortality. Clinical signs of consolidation worsen, while rationalising antibiotic therapy within three days of ICU admission improves mortality for community-acquired pneumonia patients.

The effect of adsorption, filter material and point of dilution on antibiotic elimination by haemofiltration - An in vitro study of levofloxacin

We studied an in vitro model of continuous venous-venous haemofiltration (CVVH), into which levofloxacin 100 mg was infused, to determine levofloxacin adsorption and to determine the effect of filter material and point of dilution (pre- or post-filter) on sieving coefficient. Mean (standard deviation; S.D.) adsorption was 18.7 (5.3) mg for the polyamide filter and 40.2 (2.0) mg for the polyacrylonitrile (PAN) filter (P < 0.001). Post-dilution resulted in a minor, but statistically significant, decrease in sieving coefficient (pre-dilution 0.96 (S.D. 0.10), post-dilution 0.88 (S.D. 0.11) with the PAN filter. These data indicate that the variability in published values for levofloxacin sieving coefficient are not due to variation in point of dilution or membrane type (PAN or polyamide). Significant adsorption of levofloxacin onto PAN filters occurs. (C) 2004 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Stability of benzylpenicillin during continuous home intravenous therapy

Objectives: The aim of this study was to investigate the temperature profile of home intravenous (iv) antibiotic reservoirs and the stability of 16 megaunits of benzylpenicillin sodium in 120 mL of sodium chloride 0.9% at constant and variable temperatures. Methods: A Tinytag computerized thermometer recorded temperatures every minute in the home iv antibiotic reservoir pouches of nine patients over a 24 h period. Similar bags containing benzylpenicillin sodium (16 megaunits) were maintained either at a constant 36degreesC, 26degreesC or 21-22degreesC or were worn in a pouch by five healthy volunteers for a 24 h period. Other bags were stored at 3-5degreesC for 10 days. The bags were sampled at timed intervals and benzylpenicillin concentrations assayed by HPLC. Results: Median temperatures recorded in the infusion bags worn by the nine patients were in the range 16.7-34.1degreesC. For infusion bags maintained at 36degreesC, 26degreesC and 21-22degreesC, the concentrations of benzylpenicillin dropped below 90% of the initial concentration at a mean time of 5 h 18 min, 12 h 54 min and 13 h 20 min, respectively, whereas for bags worn by the healthy volunteers the mean time for 10% loss of benzylpenicillin was 9 h 20 min. In contrast, at 3-5degreesC, concentrations of benzylpenicillin only dropped below 90% of the initial concentration at 8 days. Conclusions: Significant temperature-dependent degradation of benzylpenicillin occurs during continuous home iv antibiotic programme infusions, which could result in loss of efficacy.

Antibiotic susceptibilities of Pseudomonas aeruginosa isolates derived from patients with cystic fibrosis under aerobic, anaerobic, and biofilm conditions

Recent studies have determined that Pseudomonas aeruginosa can live in a biofilm mode within hypoxic mucus in the airways of patients with cystic fibrosis (CF). P. aeruginosa grown under anaerobic and biofilm conditions may better approximate in vivo growth conditions in the CF airways, and combination antibiotic susceptibility testing of anaerobically and biofilm-grown isolates may be more relevant than traditional susceptibility testing under planktonic aerobic conditions. We tested 16 multidrug-resistant isolates of P. aeruginosa derived from CF patients using multiple combination bactericidal testing to compare the efficacies of double and triple antibiotic combinations against the isolates grown under traditional aerobic planktonic conditions, in planktonic anaerobic conditions, and in biofilm mode. Both anaerobically grown and biofilm-grown bacteria were significantly less susceptible (P < 0.01) to single and combination antibiotics than corresponding aerobic planktonically grown isolates. Furthermore, the antibiotic combinations that were bactericidal under anaerobic conditions were often different from those that were bactericidal against the same organisms grown as biofilms. The most effective combinations under all conditions were colistin (tested at concentrations suitable for nebulization) either alone or in combination with tobramycin (10 mu g ml(-1)), followed by meropenem combined with tobramycin or ciprofloxacin. The findings of this study illustrate that antibiotic sensitivities are dependent on culture conditions and highlight the complexities of choosing appropriate combination therapy for multidrug-resistant P. aeruginosa in the CF lung.

Is Lactobacillus rhamnosus GG effective in preventing the onset of antibiotic-associated diarrhoea: A systematic review

Objective: To evaluate the efficacy of Lactobacillus rhamnosus GG in the prevention of antibiotic-associated diarrhoea. Data Sources: A computer-based search of MED-LINE, CINAHL, AMED, the Cochrane Controlled Trials Register and the Cochrane Database of Systematic Reviews was conducted. A hand-search of the bibliographies of relevant papers and previous meta-analyses was undertaken. Review Methods: Trials were included in the review if they compared the effects of L. rhamnosus GG and placebo and listed diarrhoea as a primary end-point. Studies were excluded if they were not placebo-controlled or utilised other probiotic strains. Results:Six trials were found that met all eligibility requirements. Significant statistical heterogeneity of the trials precluded meta-analysis. Four of the six trials found a significant reduction in the risk of antibiotic-associated diarrhoea with co-administration of Lactobacillus GG. One of the trials found a reduced number of days with antibiotic-induced diarrhoea with Lactobacillus GG administration, whilst the final trial found no benefit of Lactobacillus GG supplementation. Conclusion: Additional research is needed to further clarify the effectiveness of Lactobacillus GG in the prevention of antibiotic-associated diarrhoea. Copyright (c) 2005 S. Karger AG, Basel.