Risk factors for surgical wound infection and bacteraemia following coronary artery bypass surgery.

BACKGROUND: There has been no consensus from previous studies of risk factors for surgical wound infections (SWI) and postoperative bacteraemia for patients undergoing coronary artery bypass graft (CABG) surgery. METHODS: Data on 15 potential risk factors were prospectively collected on all patients undergoing CABG surgery during a 12-month period. RESULTS: Of 693 patients, 62 developed 65 SWI using the Centres for Disease Control definition: 23 were sternal wound infections and 42 were arm or leg wound infections at the site of conduit harvest. There were 19 episodes of postoperative bacteraemia. Multivariate analysis revealed that: (i) diabetes, obesity and previous cardiovascular procedure were independent predictors of SWI; and (ii) obesity was an independent risk factor for postoperative bacteraemia. CONCLUSIONS: These findings suggest that improved diabetic control and pre-operative weight reduction may result in a decrease in the incidence of SWI. But further prospective studies need to be undertaken to examine (i) whether the increased SWI risk in diabetes occurs with both insulin- and non-insulin-requiring diabetes, and whether improved peri-operative diabetes control decreases SWI; and (ii) what degree of obesity confers a risk of SWI and postoperative bacteraemia, and whether pre-operative weight reduction, if a realistic strategy in this patient group, results in a decrease in SWI.

Cephalosporin clinical concentration-time profile modelling and in-vitro bactericidal effects on Escherichia coli.

We assessed the cephalosporin concentration-time curve area (AUC), peak concentration, maintained concentration and duration of exposure on in-vitro bactericidal effects on Escherichia coli NCTC 10418, using exposures modelling cephazolin clinical profiles after 1 g and 2 g i.m. injection, equal AUC exposures (288 mg x h/L, 576 mg x h/L; 48 h) and constant exposures to 6, 12 and 24 mg/L. Cephalosporin dosage exposures based on maintenance of concentrations at multiples (6-24 times) of the MIC were not as effective in early or sustained (24 h) bactericidal effect as exposures modelling im injection profiles with equal or lower AUC (P<0.05, ANOVA). Similar results applied to i.m. comparisons with equal AUC exposures modelling extremes of concentration and time exposures. These results indicate a need for intermittent dosage to produce optimally effective profiles, and raise the possibility that these optimum dosing profiles may allow an extension of minimum interdose intervals beyond 8 h.

Tuberculous pancreatic abscess in an HIV antibody-negative patient: case report and review.

Tuberculosis (TB) is most commonly diagnosed as a pulmonary disease; however, haematogenous spread of the organism can cause disease in any organ system. We report the case of a 30-y-old woman, Human Immunodeficiency Virus (HIV) antibody-negative, who was diagnosed as having a pancreatic mass on computed tomographic (CT) scans. She underwent a laparotomy and the fluid drained from the mass was culture-positive for Mycobacterium tuberculosis. We review the clinical details of 37 similar cases of pancreatic TB in the literature, where each patient's HIV antibody status is negative or unknown. In this series 3 patients died (1 of these had commenced anti-TB therapy, the others had not) but the remaining 34 responded well to radiological-guided drainage and/or surgical intervention and anti-TB therapy. TB should be considered in the differential diagnosis of a pancreatic mass, especially when associated with epigastric pain or discomfort and weight loss.

Changes in MIC alter responses of Pseudomonas aeruginosa to tobramycin exposure.

The pharmacokinetic parameters determining antibiotic efficacy are peak concentrations (Cmax), minimum (trough) concentrations (Cmin), and area under the concentration-time curve (AUC). There is general agreement about the importance of Cmax and AUC for aminoglycosides, but this is not so for maintenance of Cmin. With in vitro exposures modelling in vivo administration, Pseudomonas aeruginosa reference strain ATCC 27853 (MIC, 1 mg/liter) and a higher-MIC (relatively resistant) clinical isolate (MIC, 4 mg/liter) were used to explore bacteriostatic and bactericidal outcomes. With P. aeruginosa ATCC 27853, kill followed a complete bolus profile with a 30-min postdistribution peak (Cpeak30) of 10 mg/liter. The clinical isolate required a Cpeak30 bolus profile of 20 mg/liter for kill, and there was no difference between the efficacies of the bolus and infusion exposures. Bolus profiles that were truncated at 8.5 h and producing sublethal effects were then combined with a wide range of Cmins. With a Cpeak30 profile of 8 mg/liter, P. aeruginosa ATCC 27853 showed a graded bacteriostatic response until a Cmin of > or = 0.8 mg/liter, when complete kill resulted. In contrast, bactericidal effects on the clinical isolate required a Cpeak30 profile of 18 mg/liter with a Cmin of > or = 1.0 mg/liter. Therefore, Cmin also contributes to the bactericidal effect of tobramycin, with requirements showing minor variation with change in MIC. Dosing principles for relatively resistant (higher-MIC) organisms are suggested from the data. Relatively higher aminoglycoside doses via infusion regimens are likely to be needed to generate higher peak concentrations and higher AUC values necessary for bactericidal effect in resistant organisms. Maintenance of trough concentrations on the order of 1.0 mg/liter during the interdose interval will tend to guard against the possibility of inadequate peak and AUC exposures for kill.

Initial concentration-time profile of gentamicin determines efficacy against Enterobacter cloacae ATCC 13047.

In vitro studies were designed to investigate the influence of peak drug concentration (Cmax), the area under the concentration-time curve (AUC), and, consequently, the trough concentration on the bactericidal effects of gentamicin against Enterobacter cloacae (MIC, 0.5 mg/liter) by simulating bolus versus infusion administration and bolus dosing with altered drug clearance. Bacteria in the lag phase were exposed to gentamicin concentration-time profiles modelling either bolus or infusion dosing (AUC constant, Cmax changing) with 30-min postdose peak concentrations (Cpeak30) of 4, 6, 8, and 10 mg/liter or bolus dosing with normal and double drug clearance (Cmax constant, AUC changing) corresponding to normal clearance profiles with Cpeak30 of 6 and 8 mg/liter. Exposure to gentamicin caused early bactericidal effects apparent by 2 h, followed by variable bacteriostatic and recovery phases. Exposure to bolus profiles resulted in greater bactericidal activity than the corresponding infusion profile up to a Cpeak30 of 8 mg/liter. At a Cpeak30 of 10 mg/liter, there were no differences in bactericidal effect. Double clearance profiles had a reduced bactericidal effect at 6 mg/liter compared to the corresponding normal clearance profile, but no differences in bactericidal effect were observed for 8-mg/liter double and normal clearance profiles. These results suggest that the initial exposure (i.e., 0 to 30 min) is a more important determinant for bacterial killing than the AUC or trough concentration for this bacterium. Subject to confirmation of these findings with other gram-negative bacteria, to optimize aminoglycoside efficacy the initial exposure (Cmax) should be maximized by giving higher doses or bolus administration at intervals which may not produce detectable trough concentrations. Clinical trials with a broad range of patients, especially those with higher clearance, would confirm these in vitro observations and define optimal dosing recommendations.

Investigation of an apparent cluster of Klebsiella pneumoniae bacteremias using random amplified polymorphic DNA analysis.

A cluster of bacteremia episodes with Klebsiella pneumoniae was noted in patients in a hematology-oncology ward during a 3-week period. Random amplified polymorphic DNA (RAPD) analysis, a novel technique for generating chromosomal fingerprints from bacterial isolates, was used as an aid to the epidemiological investigation of this cluster. For each of the two patients from whom multiple isolates had been obtained, identical RAPD patterns were observed in the serial isolates, even for a patient where the isolates had different biotypes. Isolates from different patients gave distinct patterns. Random amplified polymorphic DNA was found to be a useful typing technique for this cluster of K pneumonia bacteremias.

Parvovirus B19 in HIV infection: a treatable cause of anemia.

We describe the case of an adult male patient with AIDS who presented with severe anemia and on investigation was found to have red cell aplasia due to parvovirus B19 infection. Bone marrow examination revealed absence of erythroid development and rare giant pronormoblasts. Repeated serological examinations revealed a low level of parvovirus IgM but no IgG. Viremia was demonstrated by electron microscopy and by the polymerase chain reaction (PCR). The patient's initial hemoglobin was 45 g/l and over a four month period he required twenty units of blood. He was treated with intravenous immunoglobulin (Intragam, CSL) at a dose of 400 mg/kg/day for five days. This led to an increase in his hemoglobin to 135 g/l. Parvovirus remained detectable by PCR but not by electron microscopy. Six months later the patient relapsed (Hb 65 g/l). Again he was transfused and treated with intravenous immunoglobulin for five days. His hemoglobin rose to 153 g/l and remained stable. He subsequently received maintenance treatment with 30 g of intagram once a month. We recommend that parvovirus be considered in any HIV infected patient with recurrent anemia.

Kill kinetics and regrowth patterns of Pseudomonas aeruginosa exposed to concentration-time profiles of tobramycin simulating in vivo infusion and bolus dosing.

Pseudomonas aeruginosa ATCC 27853 was exposed to tobramycin concentration-time profiles modelling in vivo bolus and infusion dosing. Dependence of bactericidal and bacteriostatic activity on the initial profile of peak concentration (bolus effect > infusion) and area under the antibiotic concentration-time curve was observed at peak concentration/MIC ratios of 10 or below.

Minimisation of aminoglycoside toxicity in patients with cystic fibrosis.

BACKGROUND: There is evidence that administration of higher doses of aminoglycosides given less frequently improves the bactericidal effect and reduces the potential to cause side effects. To investigate this, a prospectively randomised open label therapeutic trial was undertaken in stratified groups of patients with cystic fibrosis to examine the efficacy and toxic potential of an aminoglycoside dosing regimen designed to generate high peak drug concentrations at 12 hourly intervals compared with conventional dosing at eight hourly intervals. METHODS: Patients in group A received tobramycin eight hourly using a dose aimed at generating a peak concentration of 10 mg/l with trough concentrations below 2 mg/l, and those in group B received the total daily dose required to achieve eight hourly target concentrations administered as two equal 12 hourly doses. Clinical outcomes measured and assessed included vestibular symptoms, hearing and renal function, length of hospital stay, readmission rate, and mortality. RESULTS: Twenty nine patients were recruited during a six month period, 20 to group A and nine to group B. The average peak tobramycin level was higher in group B (12.5 (2.2) mg/l) than in group A (7.9 (1.9) mg/l), whilst the average trough level was higher in group A (0.8 (0.3) mg/l) than in group B (0.5 (0.2) mg/l). There was a difference in the number of ototoxic events between patients in group A (seven of 18, 38.9%) and group B (none of eight), but no difference was found in other outcome measures assessed. CONCLUSIONS: These results suggest that 12 hourly high peak aminoglycoside dosing may be less toxic than equivalent eight hourly dosing, without any apparent difference in efficacy.

Aminoglycoside dosing: one, two or three times a day?

The safety and efficacy of conventional aminoglycoside dosing regimens have been proven in clinical trials. Higher doses at longer intervals may be more effective if they result in higher peak serum levels of the drug, but few trials of "once-a-day" dosing have shown improved clinical outcome. The clinical safety of allowing trough serum levels to fall below the minimum inhibitory concentration is not established. Literal "once-a-day" dosing will result in drug accumulation and toxicity in patients with reduced renal clearance, and in potential lack of efficacy and the emergence of antibiotic-resistant organisms in those with increased renal clearance. However, modified "once-a-day" dosing, with the interval determined by the individual's renal clearance rate (hence avoiding subtherapeutic trough levels), will avoid these problems.

The usage and costs of health services for HIV infection in Australia.

OBJECTIVE: To describe patterns of health-service usage and the resulting costs in 1992-1993 for Australian men. DESIGN: A prospective survey, stratified by phase of illness. SETTING: Hospital and community-based care. PATIENTS: A total of 128 homosexual men: 20 in phase 1 (CD4+ count > or = 500 x 10(6)/l), 31 in phase 2 (CD4+ count < 500 and > or = 200 x 10(6)/l), 30 in phase 3 (CD4+ count < 200 x 10(6)/l), and 47 in phase 4 (AIDS). MAIN OUTCOME MEASURES: Mean monthly service usage rates and costs. RESULTS: Health-service utilization increased and became more hospital-based as illness worsened; the main exception was use of antiretroviral drugs, which peaked in phases 2 and 3. Hospital admission was rare before diagnosis of AIDS. Hospital bed-days per patient per month averaged 3.3 for AIDS patients until the final 3 months of life increasing to 15.8 in the 3 months before death. Mean monthly costs (in 1992-1993 Australian dollars) were $331 [95% confidence interval (CI), 218-455] in phase 1, $667 (95% CI, 540-836) in phase 2, $1372 (95% CI, 1044-1776) in phase 3, and $4615 (95% CI, 3456-5985) for AIDS patients until the last 3 months of life and $13,308 (95% CI, 10,538-16,516) in the 3 months before death. Drugs comprised 57% of total costs in phase 1, but only 30% of costs for patients with AIDS, whereas hospital bed-days comprised 10% of phase 1 costs and 60% of AIDS costs. CONCLUSIONS: Health-care utilization and resulting costs increased with severity of illness, and were particularly high for AIDS patients in the 3 months before death. Service-utilization patterns and components of costs varied between each phase.

Photoemission studies of high-tc superconductors: the superconducting gap.

Over the last several years there have been great improvements in the energy resolution and detection efficiency of angle-resolved photoemission spectroscopy. These improvements have made it possible to discover a number of fascinating features in the electronic structure of the high transition temperature (T(c)) superconductors: apparently bandlike Fermi surfaces, flat-band saddle points, and nested Fermi surface sections. Recent work suggests that these features, previously thought explainable only by one-electron band theory, may be better understood with a many-body approach. Furthermore, other properties of the high-T(c) superconductors, which are difficult to understand with band theory, are well described using a many-body picture. Angle-resolved photoemission spectroscopy has also been used to investigate the nature of the superconducting pairing state, revealing an anisotropic gap consistent with a d-wave order parameter and fueling the current debate over s-wave versus d-wave superconductivity.

Bactericidal effect of gentamicin trough concentration provides a rationale for administration of bolus doses and maintenance of trough levels.

An in-vitro study was made of the influence of trough gentamicin concentrations (Cmin) on the bactericidal effect of gentamicin against Escherichia coli NCTC 10418. Lag phase bacterial cells were exposed in vitro to gentamicin concentration versus time profiles which modelled profiles in patients up to 30 min after either an 80 mg iv bolus over 1 min or a 30 min infusion. The gentamicin was removed 30 min post-dose and the cultures were reconstituted in broth containing a constant trough gentamicin concentration in the range of 0-3 mg/L. Bacterial cfu counts and gentamicin concentrations were measured before and during antibiotic exposure. It was found that antibacterial activity was not determined by AUC, but rather there was a threshold trough concentration producing a bactericidal effect which differed between bolus and infusion profiles. With the bolus profile trough concentrations required for a bactericidal effect were 0.5-1.0 mg/L, while with the infusion profile generating an identical post-distribution peak concentration, trough concentrations required for a sustained bactericidal effect were 2.5-3.0 mg/L. These findings favour bolus iv gentamicin dosing over infusion dosing, provided appropriate attention is paid to any potential toxicity associated with high peak concentrations. Trough data indicate the likely need to maintain critical trough concentrations by choice of appropriate intervals between doses.