Antimicrobial use and microbiological testing in district general hospital ICUs of the Veneto region of north-east Italy.

International - predominantly American - studies undertaken in the ICUs of teaching centres show that inadequate antibiotic therapy increases mortality and length of stay. We sought to ascertain whether this also pertains to smaller ICUs in the Veneto region of north-east Italy. To the best of our knowledge, this is the first such survey in the Veneto area or in Italy as a whole. A retrospective, observational study was performed across five general-hospital ICUs to examine appropriateness of microbiological sampling, empirical antibiotic adequacy, and outcomes. Among 911 patients (mean age, 65.8 years ± 16.2 SD; median ICU stay, 17.0 days [IQR, 8.0-29.0]), 757 (83.1 %) were given empirical antibiotics. Treatment adequacy could be fully assessed in only 212 patients (28.0 %), who received empirical treatment and who had a relevant clinical sample collected at the initiation of this antibiotic (T0). Many other patients only had delayed microbiological investigation of their infections between day 1 and day 10 of therapy. Mortality was significantly higher among the 34.9 % of patients receiving inadequate treatment (48.6 % vs 18.80 %; p < 0.001). Only 32.5 % of combination regimens comprised a broad-spectrum Gram-negative ß-lactam plus an anti-MRSA agent, and many combinations were irrational. Inadequate treatment was frequent and was strongly associated with mortality; moreover, there was delayed microbiological investigation of many infections, precluding appropriate treatment modification and de-escalation. Improvements in these aspects and in antibiotic stewardship are being sought.

Septic shock, pneumonia, and soft tissue infection due to Myroides odoratimimus: report of a case and review of Myroides infections.

The genus Myroides comprises aerobic, yellow-pigmented, non-motile, non-fermenting gram-negative rods formerly classified as Flavobacterium odoratum. Members of the genus are widely distributed in the environment, especially in water, and usually behave as low-grade opportunistic pathogens, having been found to cause urinary tract infection, endocarditis, ventriculitis, and cutaneous infections in severely immunocompromised patients. We report a case of soft tissue infection, septic shock, and pneumonia due to M. odoratimimus in an immunocompetent male. To our knowledge, this is the first description of life-threatening infection caused by this organism in an immunocompetent host. We have also reviewed the medical literature on the genus Myroides.

Scientific lessons from the first influenza pandemic of the 20th century.

Re-analysis of the influenza pandemic of 1918 has given reassurance about a rather low reproductive number (R(o)), a prolonged herald wave of virus and that the skewed mortality towards the young adult could be a singularly unique event dependent upon previous infection history, perhaps not to be repeated in a future pandemic. Over 99% of those who contracted the virus survived, in spite of the absence of antivirals, vaccine and antibiotics for the secondary bacteria infections which probably accounted for one-third of the 50 million deaths. Therefore, in spite of a three-fold population increase since 1918 and 100 thousand plane journeys daily, judicious and careful planning together with a stockpile of antiviral drugs, oseltamivir, zanamivir and M2 blockers and a generic H5N1 vaccine, and application of hygiene would be expected to reduce mortality in a new pandemic, to figures significantly less than 1918.

Effects of feeding blends of grains naturally contaminated with Fusarium mycotoxins on performance, metabolism, hematology, and immunocompetence of ducklings.

Experiments were conducted to determine the effects of feeding grains naturally contaminated with Fusarium mycotoxins on performance, metabolism, hematology, and immune competence of ducklings. Four hundred sixty-four 1-d-old White Pekin male ducklings were fed starter (0 to 2 wk), grower (3 to 4 wk), and finisher (5 to 6 wk) diets formulated with uncontaminated grains, a low level of contaminated grains, a high level of contaminated grains, or the higher level of contaminated grains + 0.2% polymeric glucomannan mycotoxin adsorbent. Body weight gains, feed consumption, and feed efficiency were not affected by diet. However, consumption of contaminated grains decreased plasma calcium concentrations after 2 wk and plasma uric acid concentrations at the 4-wk assessment point. Mean corpuscular hemoglobin concentrations and hematocrit decreased when ducks were fed contaminated grains for 4 or 6 wk, respectively. In contrast, total numbers of white blood cells and lymphocytes increased transiently in birds fed contaminated grains for 4 wk. The antibody response to sheep red blood cells (CD4+ T cell dependent) and the cell-mediated response to phytohemagglutinin-P (also CD4+ T cell dependent) were not affected by diet, but consumption of contaminated grains for 6 wk decreased the duration of peak cell-mediated response to dinitrochlorobenzene (CD8+ T cell dependent) assessed in a skin test. Feeding grains naturally contaminated with Fusarium mycotoxins, even at levels widely regarded as high, exerted only minor adverse effects on plasma chemistry and hematology of ducklings, and production parameters were unaffected in this avian species. Mycotoxin-contaminated feeds may, however, render these animals susceptible to infectious agents such as viruses against which the CD8+ T cell provides necessary defence. Glucomannan mycotoxin adsorbent was not effective in preventing alterations caused by Fusarium mycotoxins.

Broiler performance and intestinal alterations when fed drug-free diets.

A study was carried out to investigate the effects of a drug-free feeding program on broiler performance and intestinal morphology. Chicks vaccinated against coccidia were randomly assigned to 4 dietary treatments: 1) negative control (NC), basal diet; 2) positive control (PC), diet 1 + Lincomycin; 3) program 1 (PG1); diet 1 + Bio-Mos, Vegpro, MTB-100, Acid Pak 4-Way, and All-Lac XCL; 4) and program 2 (PG2), diet 1 + Bio-Mos and All-Lac XCL, each of which were assigned to 13 pens (48 birds in each of 52 pens). Growth traits (BW, feed intake, yield, mortality, BW gain, and feed conversion rate) were obtained through 49 d. At d 14, 3 chicks per pen were challenged with coccidia. Segments of duodenum, ileum, and ceca were removed to measure intestinal morphology at d 14, 28, 35, and 49. Final BW gain of broilers on PC (2.736 kg) was numerically higher than those for NC (2.650 kg). Cumulative feed conversion rate at d 49 was improved (P < 0.05) in birds consuming PC and PG2 compared with NC. Overall, mortality was higher for birds consuming the NC (P < 0.05) than the PC, PG1, and PG2 diets. Interaction of dietary treatments with age and age alone were evident (P < 0.0001) for morphology of duodenum, ileum, and ceca. Lamina propria in ceca was thicker (P < 0.008) in broilers consuming the NC than PG1 and PG2 diets. The results of this study indicated that feeding birds without growth promoters resulted in higher mortality and decreased growth performance than did feeding a diet with an antibiotic, and the combination of Bio-Mos and All-Lac XCL helped to reduce negative effects.

A hypothesis: the conjunction of soldiers, gas, pigs, ducks, geese and horses in northern France during the Great War provided the conditions for the emergence of the "Spanish" influenza pandemic of 1918-1919.

The Great Influenza Pandemic of 1918-1919 was a cataclysmic outbreak of infection wherein over 50 million people died worldwide within 18 months. The question of the origin is important because most influenza surveillance at present is focussed on S.E. Asia. Two later pandemic viruses in 1957 and 1968 arose in this region. However we present evidence that early outbreaks of a new disease with rapid onset and spreadability, high mortality in young soldiers in the British base camp at Etaples in Northern France in the winter of 1917 is, at least to date, the most likely focus of origin of the pandemic. Pathologists working at Etaples and Aldershot barracks later agreed that these early outbreaks in army camps were the same disease as the infection wave of influenza in 1918. The Etaples camp had the necessary mixture of factors for emergence of pandemic influenza including overcrowding (with 100,000 soldiers daily changing), live pigs, and nearby live geese, duck and chicken markets, horses and an additional factor 24 gases (some of them mutagenic) used in large 100 ton quantities to contaminate soldiers and the landscape. The final trigger for the ensuing pandemic was the return of millions of soldiers to their homelands around the entire world in the autumn of 1918.

Effect of poultry diet on phosphorus in runoff from soils amended with poultry manure and compost.

Phosphorus in runoff from fields where poultry litter is surface-applied is an environmental concern. We investigated the effect of adding phytase and reducing supplemental P in poultry diets and composting poultry manures, with and without Fe and Al amendments, on P in manures, composts, and runoff. We used four diets: normal (no phytase) with 0.4% supplemental P, normal + phytase, phytase + 0.3% P, and phytase + 0.2% P. Adding phytase and decreasing supplemental P in diets reduced total P but increased water-extractable P in manure. Compared with manures, composting reduced both total P, due to dilution of manure with woodchips and straw, and water-extractable P, but beyond a dilution effect so that the ratio of water-extractable P to total P was less in compost than manure. Adding Fe and Al during composting did not consistently change total P or water-extractable P. Manures and composts were surface-applied to soil boxes at a rate of 50 kg total P ha(-1) and subjected to simulated rainfall, with runoff collected for 30 min. For manures, phytase and decreased P in diets had no significant effect on total P or molybdate-reactive P loads (kg ha(-1)) in runoff. Composting reduced total P and molybdate-reactive P loads in runoff, and adding Fe and Al to compost reduced total P but not molybdate-reactive P loads in runoff. Molybdate-reactive P in runoff (mg box(-1)) was well correlated to water-extractable P applied to boxes (mg box(-1)) in manures and composts. Therefore, the final environmental impact of dietary phytase will depend on the management of poultry diets, manure, and farm-scale P balances.

Post-exposure prophylaxis of systemic anthrax in mice and treatment with fluoroquinolones.

OBJECTIVES: To compare the fluoroquinolones gatifloxacin and moxifloxacin with ciprofloxacin for post-exposure prophylaxis of systemic anthrax in a BALB/c mouse model. METHODS: Treated mice and controls were inoculated subcutaneously with 5 x 10(4) spores/mouse of Bacillus anthracis Ames strain and observed for 37 days after challenge. Treated mice were given 100 mg/kg of antibiotic orally twice daily for 14 days, starting at various times post-challenge. RESULTS: Treatment starting 6 h post-challenge resulted in survival rates of 90%, 15% and 40% for gatifloxacin, moxifloxacin and ciprofloxacin, respectively. Treatment commencing 24 h post-challenge resulted in survival rates of 65%, 10% and 5%, respectively. Treatment starting more than 24 h after exposure had little effect on survival. CONCLUSIONS: Gatifloxacin appeared to be more effective than moxifloxacin or ciprofloxacin, at similar doses, for early post-exposure treatment of murine systemic anthrax. However, these results might be due to differences in potency or pharmacokinetic properties.

An alternative to antibiotic-based drugs in feed for enhancing performance of broilers grown on Eimeria spp.-infected litter.

Three trials were conducted to evaluate the effects of lasalocid, an anticoccidial feed additive (90.7 kg/ton); bacitracin, a growth-promoter (50 g/ton); and yeast culture residue (YCR) (1 kg/ton) on the performance of broiler chicks reared to 42 d of age on recycled litter. Recycled litter consisted of pine wood shavings containing droppings from chicks infected with 3 select strains of coccidia (Eimeria tenella, Eimeria maxima, and Eimeria acervulina). Response variables (BW, intestinal tract and litter coliform counts, cecal and liver relative weights, and litter moisture content) were recorded biweekly. Mean BW of chicks fed the diet supplemented with YCR was higher than that of the controls (P < 0.05) and comparable to that of the lasalocid-treated birds in all 3 trials. Mean BW of chicks in all treatment groups decreased uniformly as the litter aged and moisture content increased. The mean intestinal coliform population from YCR-treated chicks was lower (P < 0.05) than those of the control and lasalocid populations. The coliform count was consistently lower than that in chicks on a bacitracin-supplemented diet. Coliform counts from the control and lasalocid-treated birds did not differ. The litter coliform counts increased with increased use of the litter. Cecal and liver relative weights calculated from the chicks in trial 3 showed that only the liver was significantly affected by treatments. YCR appeared to be a viable alternative to bacitracin and lasalocid medication in enhancing growth of broiler chicks reared on recycled litter.

Effects of feeding blends of grains naturally contaminated with Fusarium mycotoxins on production and metabolism in broilers.

Three hundred sixty, 1-d-old male broiler chicks were fed diets containing grains naturally contaminated with Fusarium mycotoxins for 56 d. The four diets included control (0.14 mg/kg deoxynivalenol, 18 mg/ kg fusaric acid, < 0.1 mg/kg zearalenone), low level of contaminated grains (4.7 mg/kg deoxynivalenol, 20.6 mg/kg fusaric acid, 0.2 mg/kg zearalenone), and high level of contaminated grains without (8.2 mg/kg deoxynivalenol, 20.3 mg/kg fusaric acid, 0.56 mg/kg zearalenone) and with (9.7 mg/kg deoxynivalenol, 21.6 mg/kg fusaric acid, 0.8 mg/kg zearalenone) 0.2% esterified-glucomannan polymer derived from Saccharomyces cerevisiae1026 (E-GM). Body weight gain and feed consumption responded in a significant quadratic fashion to the inclusion of contaminated grains during the finisher period. Efficiency of feed utilization, however, was not affected by diets. The feeding of contaminated grains in the finisher period also caused significant linear increases in blood erythrocyte count and serum uric acid concentration and a significant linear decline in the serum lipase activity. Dietary inclusion of contaminated grains resulted in a significant quadratic effect on serum albumin and y-glutamyltransferase activity. Blood hemoglobin and biliary IgA concentrations, however, responded in significant linear and quadratic fashions. Supplementation of E-GM counteracted most of the blood parameter alterations caused by the Fusarium mycotoxin-contaminated grains and reduced breast muscle redness. It was concluded that broiler chickens may be susceptible to Fusarium mycotoxicoses when naturally contaminated grains are fed containing a combination of mycotoxins.

Comparative in-vitro activity of penicillin alone and combined with gentamicin against clinical isolates of Streptococcus pneumoniae with decreased susceptibility to penicillin.

The worldwide emergence of Streptococcus pneumoniae with decreased susceptibility to penicillin has led to the suggestion that drug combinations might be used. The aim of this study was to determine possible synergy using a combination of penicillin with sub-inhibitory doses of gentamicin against 26 clinical isolates of S. pneumoniae with decreased susceptibility to penicillin, using half-chequerboards and killing curves. Synergy was demonstrated for ten of the 26 isolates with the combination of penicillin with gentamicin at 1 mg/l and for 22 isolates with penicillin and gentamicin at 2 mg/l. Killing curves on three isolates showed synergy and confirmed the chequerboard results. Further synergy studies using penicillin or cefotaxime/ceftriaxone, plus low dose gentamicin against penicillin-resistant pneumococci are indicated.

World War I may have allowed the emergence of "Spanish" influenza.

The 1918 influenza pandemic caused 40 million deaths, and so dwarfed in mortality and morbidity the preceding pandemic of 1889 and the 1957 and 1968 pandemics. In retrospect, much can be learnt about the source, the possible subterranean spread of virus, and the genetic basis of virulence. The World Health Organization has urged every nation to prepare a pandemic plan for the first global outbreak of the 21st century. We present an appraisal of epidemiological and mortality evidence of early outbreaks of respiratory disease in France and the UK in the years 1915 to 1917. Certain of these earlier focal outbreaks--called epidemic bronchitis rather than influenza--occurred during the winter months when influenza was known to be in circulation, and presented with a particular heliotrope cyanosis that was so prominent in the clinical diagnosis in the world pandemic outbreak of 1918-1919 (the Great Pandemic). The outbreaks in army camps at Etaples in France and Aldershot in the UK in 1916-1917 caused very high mortality in 25-35 year olds. Increased deaths from bronchopneumonia and influenza were also recorded in England. We deduce that early focal outbreaks of influenza-like disease occurred in Europe and on the balance of probability the Great Pandemic was not initiated in Spain in 1918 but in another European country in the winter of 1916 or 1917. We suggest that the pandemic had its origins on the Western Front, and that World War I was a contributor.

A double-blind placebo-controlled trial of azithromycin as an adjunct to non-surgical treatment of periodontitis in adults: clinical results.

BACKGROUND/AIMS: The aim of the study was to investigate the clinical and microbiological effects of azithromycin as an adjunct to the non-surgical treatment of periodontitis in adults. Azithromycin is an antibiotic which is taken up by phagocytes and is released over long periods in inflamed tissue but requires a total of only three doses of 500 mg to produce its therapeutic effect. METHOD: 46 patients were treated in a double-blind placebo-controlled study with assessments at weeks 0, 1, 2, 3, 6, 10 and 22. Throughout the trial measurements were made of plaque, gingival bleeding, calculus, probing pocket depths and bleeding on probing. Microbiological sampling was carried out from a selected pocket >or=6 mm at each visit. The regime employed consisted of OHI, scaling and root planing at weeks 0, 1 and 2 with reinforcement of OHI and minimal scaling at weeks 6, 10 and 22. Patients were randomly assigned to receive either azithromycin, (A), or placebo capsules, (C), 500 mg, 1x daily for 3 days at week 2. 44 patients completed the study. Mean pocket depths were analysed using analysis of covariance in 3 groups with initial pocket depth values of 1-3 mm, 4-5 mm and >or=6 mm. RESULTS: The results of the microbiology have been reported in a separate paper. The clinical data showed that by week 22 a lower % of pockets initially >5 mm deep remained above that level in the 23 patients taking azithromycin (A), than the 21 taking the placebo (C), (A, 5.6%; C, 23.3%). Also at week 22, for pockets initially 4 mm or more, the test group had fewer pockets >3 mm deep (A, 26.1%; C, 44.3%), fewer failing to improve in probing depth (A, 6.6%; C, 21.6%) and fewer continuing to bleed on probing (A, 46.9%; C, 55.6%) when compared with the control group. Pocket depths initially 4-5 mm or 6-9 mm analysed by analysis of covariance showed lower mean pocket depths in the patients on azithromycin, at weeks 6, 10 and 22, (pockets initially 4-5 mm, p<0.001 on all occasions, pockets initially 6-9 mm, p<0.001, week 6; p< 0.003, week 10; p<0.001, week 22). CONCLUSIONS: Azithromycin may be a useful adjunct in the treatment of adult periodontitis, particularly where deep pockets are present.

Effects of hen age, Bio-Mos, and Flavomycin on poult susceptibility to oral Escherichia coli challenge.

The effects of hen age, Escherichia coli, and dietary Bio-Mos and Flavomycin on poult performance from 1 to 21 d were studied. Day-of-hatch BUTA (BIG-6) male poults were gavaged orally (1 mL) with approximately 10(8) cfu/mL E. coli composed of four serotypes or sterile carrier broth. A mixture of the same E. coli cultures was added to the poults' water troughs to attain a concentration of approximately 10(6) cfu/mL on a weekly basis to ensure a continuous bacterial challenge. Within each E. coli split plot treatment group, poults from hens of different ages (33 and 58 wk of age) were fed diets containing Bio-Mos (1 g/kg feed), Flavomycin (2.2 mg active ingredient/kg feed), Bio-Mos plus Flavomycin, or a control diet, in a randomized complete block design. This experiment yielded eight treatments per challenge group. At Weeks 1 and 3, eight birds from each treatment from the E. coli challenged and unchallenged groups were randomly chosen for bacterial sampling of liver and intestinal tissue for coliforms, aerobic bacteria, and Lactobacillus spp. E. coli isolates from tissue samples were O serotyped. During E. coli challenge, dietary Bio-Mos and Flavomycin improved poult BW and BW gains (P < or = 0.05). When poults were not challenged with E. coli, poults from old hens had improved BW and cumulative BW gains over poults from young hens (P < or = 0.05). Cumulative 3-wk BW gains for unchallenged poults from young hens were improved by Bio-Mos and Flavomycin (P < or = 0.05) alone and in combination when compared to the control diet. Two of the four E. coli serotypes administered were recovered. Several serotypes were recovered that were not administered. It may be concluded that dietary Bio-Mos and Flavomycin can improve the overall performance of poults, especially when they are faced with an E. coli challenge.

Multiple mutations modulate the function of dihydrofolate reductase in trimethoprim-resistant Streptococcus pneumoniae.

Trimethoprim resistance in Streptococcus pneumoniae can be conferred by a single amino acid substitution (I100-L) in dihydrofolate reductase (DHFR), but resistant clinical isolates usually carry multiple DHFR mutations. DHFR genes from five trimethoprim-resistant isolates from the United Kingdom were compared to susceptible isolates and used to transform a susceptible control strain (CP1015). All trimethoprim-resistant isolates and transformants contained the I100-L mutation. The properties of DHFRs from transformants with different combinations of mutations were compared. In a transformant with only the I100-L mutation (R12/T2) and a D92-A mutation also found in the DHFRs of susceptible isolates, the enzyme was much more resistant to trimethoprim inhibition (50% inhibitory concentration [IC50], 4.2 microM) than was the DHFR from strain CP1015 (IC50, 0.09 microM). However, Km values indicated a lower affinity for the enzyme's natural substrates (Km for dihydrofolate [DHF], 3.1 microM for CP1015 and 27.5 microM for R12/T2) and a twofold decrease in the specificity constant. In transformants with additional mutations in the C-terminal portion of the enzyme, Km values for DHF were reduced (9.2 to 15.2 microM), indicating compensation for the lower affinity generated by I100-L. Additional mutations in the N-terminal portion of the enzyme were associated with up to threefold-increased resistance to trimethoprim (IC50 of up to 13.7 microM). It is postulated that carriage of the mutation M53-I-which, like I100-L, corresponds to a trimethoprim binding site in the Escherichia coli DHFR-is responsible for this increase. This study demonstrates that although the I100-L mutation alone may give rise to trimethoprim resistance, additional mutations serve to enhance resistance and modulate the effects of existing mutations on the affinity of DHFR for its natural substrates.

The impact of resistance on the management of urinary tract infections.

Urinary tract infections requiring treatment are extremely common. It is estimated that between 20 and 50% of adult women will have had at least one symptomatic urinary tract infection. When considering the optimal therapy of any infection, patient factors, organism factors, drug factors (e.g. pharmacokinetics), side-effects and cost as well as antimicrobial resistance all need to be considered. This paper deals with the impact of increasing antibiotic resistance on the management of urinary tract infections.

The Consortium of Graduate Medical Schools in Australia: formal and informal collaboration in medical education.

CONTEXT: In 1996-97 three Australian medical schools adopted 4-year graduate medical courses. The schools formed a consortium to establish common admissions processes and to collaborate on curriculum and staff development. OUTCOMES: ADMISSIONS: Outcomes in admissions included the construction of an entry test and agreement on common application procedures. Structured interviews and measures of prior tertiary performance were adopted in each school with some local variations. Formal structures were put into place to manage the development of the test and admissions procedures. OUTCOMES: CURRICULUM AND STAFF DEVELOPMENT: No formal structures were put into place for curriculum and staff development. While the advantages of common approaches were recognised, it was accepted that it was also important to generate local ownership and commitment to the new courses. Outcomes of educational consortia should not be judged solely by the nature of joint ventures but by the way in which membership of the consortium changes the priorities and practices within the institutions. Examples of the operation of this principle within the three schools include: use of visiting experts to refine and modify approaches to problem-based learning; use of staff from partner institutions to facilitate implementation of the courses; sharing information technology expertise; cooperation in the construction of feedback mechanisms, and sharing advice on fulfilling accreditation requirements. CONCLUSION: The Consortium has had an important impact on Australian medical education. There is a need for further analysis of the two methods of operation of the consortium, formal and informal, and their relation to its overall functioning.

Vancomycin resistance in Gram-positive bacteria other than Enterococcus spp.

This is a review article on vancomycin resistance on gram positive bacteria other than enterococci. Epidemiology of varying resistance, its clinical relevance and therapeutic options in infections caused by vancomycin resistant Listeria spp., Corynebacteria, streptococci and staphylocci are discussed.