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.

Co-existing conditions for deaths from infectious and parasitic diseases in Australia

Objective: To examine the frequency distribution of co-existing conditions for deaths where the underlying cause was infectious and parasitic diseases. Materials and methods: Besides the underlying cause of death, the distributions of co-existing conditions for deaths from infectious and parasitic diseases were examined in total and by various age and sex groups, at individual and chapter levels, using 1998 Australian mortality data. Results: In addition to the underlying cause of death, the average number of reported co-existing conditions for a single infectious and parasitic death was 1.62. The most common co-existing conditions were respiratory failure, acute renal failure non-specific causes, ischaemic heart disease, pneumonia and diabetes. When studying the distribution of co-existing conditions at the ICD-9 chapter level, it was found that the circulatory system diseases were the most important. There was an increasing trend in the number of reported co-existing conditions from 60 years of age upwards. Gender differences existed in the frequency of some reported co-existing conditions. The most common organism types of co-existing conditions were other bacterial infection and other viruses. Conclusions: The study indicated that the quality of death certificates is less than satisfactory for the 1998 Australian mortality data. The findings may be helpful in clarifying the ICD coding rules and the development of disease prevention strategies. (C) 2003 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Histological analysis of gallbladder diseases in relation to opisthorchiasis in endemic areas of Thailand

Chronic gallbladder disease frequently accompanies infection with the liver fluke, Opisthorchis viverrini, in Northeast Thailand. However, the pathology and pathogenesis of the gallbladder disease have not been described. Accordingly, gallbladder specimens from 187 consecutive patients who had undergone cholecystectomy at a referral hospital in an endemic area in Thailand were histologically characterized in relation to O. viverrini infection. The infection was assessed by the presence of parasite eggs in the bile and/or antibody response to the liver fluke. The average level of parasite-specific IgG was significantly higher in patients with Opisthorchis eggs in the bile than those without (P < 0.001). The main histopathologic features of the gallbladder included inflammation, mucosal atrophy/or hyperplasia, goblet cell metaplasia, mucous gland hyperplasia, Rokitansky-Aschoff sinus formation, dysplasia and fibrosis. The fibrosis was strongly associated with elevated levels of Opisthorchis-specific antibody (P < 0.001) but not with the presence of parasite eggs. Other pathologic features did not vary in frequency or severity with parasitological status. Our results show that severe fibrosis of the gallbladder is a more common histologic feature of cholecystitis among those with O. viverrini infection compared to those without infection. The close relationship between parasite-specific IgG and severe fibrosis suggests that specific immune response to the parasite play an important role in the pathogenesis of the fibrotic change. (C) 2003 Elsevier B.V. All rights reserved.

The purine salvage enzyme hypoxanthine guanine xanthine phosphoribosyl transferase is a major target antigen for cell-mediated immunity to malaria

Although there is good evidence that immunity to the blood stages of malaria parasites can be mediated by different effector components of the adaptive immune system, target antigens for a principal component, effector CD4(+) T cells, have never been defined. We generated CD4+ T cell lines to fractions of native antigens from the blood stages of the rodent parasite, Plasmodium yoelii, and identified fraction-specific T cells that had a Th1 phenotype (producing IL-2, IFN-gamma, and tumor necrosis factor-a, but not IL-4, after antigenic stimulation). These T cells could inhibit parasite growth in recipient severe combined immunodeficient mice. N-terminal sequencing of the fraction showed identity with hypoxanthine guanine xanthine phosphoribosyl transferase (HGXPRT). Recombinant HGXPRT from the human malaria parasite, Plasmodium falciparum, activated the T cells in vitro, and immunization of normal mice with recombinant HGXPRT reduced parasite growth rates in all mice after challenge.

Mannose-binding lectin gene polymorphism predicts hospital admissions for COPD infections

Infection frequently causes exacerbations of chronic obstructive pulmonary disease (COPD). Mannose-binding lectin (MBL) is a pattern-recognition receptor that assists in clearing microorganisms. Polymorphisms in the MBL2 gene reduce serum MBL levels and are associated with risk of infection. We studied whether the MBL2 codon 54 B allele affected serum MBL levels, admissions for infective exacerbation in COPD and disease susceptibility. Polymorphism frequency was determined by PCR-RFLP in 200 COPD patients and 104 smokers with normal lung function. Serum MBL was measured as mannan-binding activity in a subgroup of 82 stable COPD patients. Frequency of COPD admissions for infective exacerbation was ascertained for a 2-year period. The MBL2 codon 54 B allele reduced serum MBL in COPD patients. In keeping, patients carrying the low MBL-producing B allele had increased risk of admission for infective exacerbation (OR 4.9, P-corrected = 0.011). No association of MBL2 genotype with susceptibility to COPD was detected. In COPD, serum MBL is regulated by polymorphism at codon 54 in its encoding gene. Low MBL-producing genotypes were associated with more frequent admissions to hospital with respiratory infection, suggesting that the MBL2 gene is disease-modifying in COPD. MBL2 genotype should be explored prospectively as a prognostic marker for infection risk in COPD.

Comparative pharmacokinetics of metronidazole in camels, sheep and goats

The pharmacokinetics of metronidazole was determined after a single intramuscular (i.m.) dose of 30 mg.kg(-1)-body weight in five camels, sheep and goats. Marked differences were found between the three species in some of the kinetic parameters. For example, the elimination half-lives t(1/2); (h) in camels, sheep and goats were 10.0, 6.21 and 5.87, respectively. The drug maximum concentrations in plasma, C-max (mg.ml(-1)), were 28.3, 54.6 and 54.4 in camels, sheep and goats, respectively. The time to reach C-max, t(max) (h), were 5, 4 and 2 in camels, sheep and goats, respectively. The mean residence times (MRT; h) in camels, sheep and goats were 16.7, 10.8 and 8.64, respectively. In the light of the present kinetic data and known microbial sensitivities of metronidazole, we recommend an i.m. dose of 15 mg.kg(-1) in camels and 10 mg.kg(-1) in sheep and boats. every 12 h.

The use of a change in gentamicin clearance as an early predictor of gentamicin-induced nephrotoxicity

A retrospective review was undertaken in 744 patients who were dose-individualized with gentamicin once daily to evaluate a change in gentamicin clearance as a potential predictor of nephrotoxicity. The definition of nephrotoxicity was chosen to be a change in creatinine clearance greater than 20%. Similarly, a change in gentamicin clearance of greater than 20% was also considered a possible index of nephrotoxicity. Four criteria were developed to assess the usefulness of gentamicin clearance as a predictor of nephrotoxicity. Following the application of the inclusion/exclusion criteria, 132 patients were available for the analysis. The sensitivity, specificity, positive predictive value, and negative predictive value were assessed for each of the criteria. Receiver operating characteristic (ROC) curves were produced to determine if an optimum value in the change of gentamicin clearance could be found to maximize sensitivity and specificity. The overall incidence of nephrotoxicity based on a decrease in creatinine clearance by 20% or more was 3.8%. Women were overrepresented in the nephrotoxic group [71.4% versus 40.1% (P = 0.0025)]. Patients with nephrotoxicity had statistically longer treatment periods, increased cumulative dose, and more dosing predictions (P < 0.05 in each case). The sensitivity of the criteria ranged from 43 to 46%, and specificity ranged from 93 to 99%. The positive and negative predictive values ranged from 63 to 94% and 86 to 89%, respectively. In those patients in whom nephrotoxicity was predicted from a change in gentamicin clearance, this change occurred on average 3 days before the change in creatinine clearance (P < 0.05). A change in gentamicin clearance to predict nephrotoxicity may be a useful addition to current monitoring methods, although it is not the complete answer.

Community-acquired methicillin-resistant Staphylococcus aureus carrying Panton-Valentine leukocidin genes: Worldwide emergence

Infections caused by community-acquired (CA)-methicillin-resistant Staphylococcus aureus (MRSA) have been reported worldwide. We assessed whether any common genetic markers existed among 117 CA-MRSA isolates from the United States, France, Switzerland, Australia, New Zealand, and Western Samoa by performing polymerase chain reaction for 24 virulence factors and the methicillin-resistance determinant. The genetic background of the strain was analyzed by pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST). The CA-MRSA strains shared a type IV SCCmec cassette and the Panton-Valentine leukocidin locus, whereas the distribution of the other toxin genes was quite specific to the strains from each continent. PFGE and MLST analysis indicated distinct genetic backgrounds associated with each geographic origin, although predominantly restricted to the agr3 background. Within each continent, the genetic background of CA-MRSA strains did not correspond to that of the hospital-acquired MRSA.

Antimicrobial resistance in Staphylococcus aureus in Australian teaching hospitals, 1989-1999

An annual survey of antimicrobial resistance in clinical isolates of Staphylococcus aureus was conducted in 21 Australian teaching hospital microbiology laboratories in eight major cities from 1989 to 1999. A total of 19,000 isolates were tested for susceptibility to 18 antimicrobials, with 3795 being methicillin-resistant (MRSA). Resistance to ciprofloxacin in MRSA increased from 4.9% to 75.9%. The proportion of MRSA resistant to erythromycin decreased significantly (99.0%-88.9%), as did that to trimethoprim (98.4%-82.4%) and to tetracycline (96.5%-80.1%). The proportion of MRSA isolated increased in Sydney, Melbourne, Canberra, Adelaide, Perth, and Darwin, but not in Brisbane. The proportion in Hobart peaked in 1994. MRSA in Perth were predominantly non-multiresistant (nmMRSA) throughout the survey (i.e., resistant to less than three of eight indicator antibiotics) due mainly to local strains that originated in the community. The proportion of nmMRSA increased to modest levels in the other cities. In eastern cities, this was due to the appearance of strains closely related to nmMRSA seen in other countries of the southwestern Pacific.