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All episodes of bloodstream infection in patients admitted to a Norwegian university hospital in 1974-1979 and in 1988-1989 were analyzed; altogether, there were 1,447 episodes involving 1,286 patients, and 54.3% of all episodes were hospital-acquired. The incidence of bloodstream infection increased between the two periods studied from 4.26/1,000 admissions to 8.71/1,000. Crude mortality rates were 27.6% and 18.8% and attributable mortality rates were 12.3% and 6.9% in the first and second periods, respectively. Patients > 60 years of age accounted for more than half of the bloodstream infections; mortality in this group was significantly higher than that among younger patients (31.4% vs. 13.9%). The frequency of isolation of Enterobacteriaceae decreased from 48% in the first period to 34% in the second, while the rate of isolation of coagulase-negative staphylococci increased from 6.5% to 16.9%. The shift in etiology may be explained in part by the occurrence of significantly more bloodstream infections related to intravascular devices, endocarditis, and skin and wound infections and of significantly fewer episodes related to abdominal or genitourinary disease in the second than in the first period. Almost all isolates of Enterobacteriaceae were susceptible to newer cephalosporins and aminoglycosides. In 1974-1979, 96 (69.1%) of 139 patients with septic shock died; in 1988-1989, the figure was 35 (52.2%) of 67 patients (P = .019). Clinical factors predictive of an adverse outcome were septic shock (odds ratio for first/second period, 12.7/4.6), intensive care treatment (not significant/10.6), malignant disease (4.6/2.6), any underlying disease (4.2/not significant), diabetes mellitus (3.6/not significant), age of > 60 years (not significant/3.0), and pulmonary source of infection (not significant/2.8).

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Sequential intravenous and oral ciprofloxacin (CF) was compared with a combination of tobramycin and cefuroxime (T/C) in the treatment of serious systemic infections. Altogether 310 patients were randomized, 160 receiving CF and 150 T/C, the 2 groups being reasonably well balanced. 29 patients without infection were excluded from the analysis. Complete clinical resolution was obtained in 75% (107/143) patients receiving CF and in 78% (107/138) receiving T/C; the difference was not statistically significant. The rate of bacterial eradication in septicaemia was 72% (95% confidence interval (95% c.i.): 58-86%) for patients treated with CF and 87% (95% c.i.: 77-96%) when T/C was given, while the eradication rates in urinary tract infection were 72% (95% c.i.: 54-90%) and 45% (95% c.i.: 23-67%) for CF and T/C, respectively. Significant differences in bacteriological response for other diagnoses were not detected. Also for lower respiratory tract infections (LTRI) the clinical and bacteriological responses were quite similar, although relatively more failures occurred in CF treated patients with LRTI caused by pneumococci. The frequencies of adverse reactions were comparable, but the reactions were less serious following CF treatment. Our results indicate that CF may be used for empirical treatment of serious infections. However, if pneumococcal etiology is likely, alternative antibiotics should be used, and if necessary, coverage against anaerobic bacteria should be added.

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During the period 1973-1984, 72 patients with infective endocarditis (IE) were hospitalized in the medical department, Bergen University Hospital. The male/female ratio was 1.25/1, the mean age 55.3 years. 35 infections were caused by streptococci, 18 by staphylococci, 6 by other microorganisms and in 13 cases no causal organism was found. Only 13 patients had rheumatic heart disease. The overall mortality was 35%, and the mean age of the patients who died was 65 years. The case fatality rates for staphylococcal and streptococcal endocarditis were 61 and 24% respectively. In the period 1973-1978 the case fatality rate was 50% compared to 26% during 1979-1984. The proportion of patients with culture-negative endocarditis was reduced from 31 to 11% from the first to the second half of the study and the percentage of patients who received antibiotics before diagnosis decreased from 81 to 58%. Valve replacement was performed in 4 patients with staphylococcal and 15 with streptococcal infections. Seven cases (mean age 73.4 years) were diagnosed at necropsy; 3 with staphylococcal infections. With increased clinical awareness of IE, liberal use of blood cultures, better diagnostic tools and earlier surgical intervention, especially in staphylococcal infections, a further reduction in mortality should be possible.

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Using an agar well diffusion assay, the concentrations of ofloxacin were measured in serum and skin blister fluid after an oral dose of 300 mg given with or without a standardized meal. The apparent lag time was longer when the drug was taken with food than in the fasting state and the serum peak concentrations occurred later; the rates of absorption being 1.72 +/- 1.12/h (S.D.) and 3.40 +/- 1.56/h respectively. The mean peak concentrations of each individual in serum and blister fluid were 3.8 +/- 1.6 mg/l and 1.7 +/- 0.5 mg/l, respectively, when the drug was taken with food, compared with 4.2 +/- 1.9 mg/l and 2.1 +/- 0.7 mg/l in the fasting state. The rate of penetration into blister fluid was not influenced by the intake of food. The elimination half-life was 9.0 +/- 6.2 h in serum and 13.5 +/- 7.8 h in blister fluid when the volunteers were fasting. The corresponding values in the non-fasting state were 6.3 +/- 5.5 h and 10.6 +/- 4.6 h. The ratio of the area under the concentration versus time curve (AUC0-infinity) for blister fluid and serum was 1.20 +/- 0.70 when ofloxacin was given without food and 1.03 +/- 0.34 when given with the meal.

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According to Pharmacopoea Nordica, steam autoclaves should be regularly monitored by a specific Swedish preparation of Bacillus stearothermophilus spores. If another biological indicator (BI) is used for such a control, it should first be calibrated against the Swedish BI (SBI) and the two BIs should be equally thermoresistant. Attest No. 1262 BI (ABI) has previously been shown to be more thermoresistant than the SBI at 134 degrees C, saturated steam. The purpose of the present study was to compare the thermoresistance of the SBI and the ABI at 121 degrees C, saturated steam and prevacuum. Seven hundred and twenty units of each BI were heat-exposed in an Emmer 760 litre prevacuum, pressure-pulsing steam autoclave. After prevacuum with steam injection (manual or automatic preconditioning), the following incremental heat exposure times were used in triplicate (20 simultaneously tested units of each BI in each cycle) according to a randomized scheme: 5, 6 1/2, 8, 9 1/2, 11, 12 1/2, 14 and 15 min. The intra-chamber pressure and temperature were continuously monitored throughout the test and equilibration cycles. The heat-exposed BI units were cultivated and read as recommended by the manufacturers. SBI and ABI showed a survival-time of 8 min and 11 min respectively, and a kill-time between 14 min and 15 min for both BIs. Thus, the ABI had the narrower survival-kill window. Probit analysis testing of the results showed that the difference in thermoresistance, at 121 degrees C, saturated steam and prevacuum between Attest No. 1262 BI and the Swedish BI mentioned in Pharmacopea Nordica was not statistically significant.

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The thermoresistance of various lots of two biological indicators (BIs) for steam sterilization control, a Scandinavian BI (SBI) and the Attest BI (ABI), were compared during sterilization cycles in a hospital prevacuum (pressure-pulsing) steam autoclave at 134 degrees C, saturated steam. ABI No. 1242, ABI No. 1262 (its replacement) and incremental heat exposure times between 0 s and 180 s were used. The intrachamber temperature and pressure were continuously measured and monitored throughout the sterilization cycles. The results showed that both of the ABIs were more thermoresistant than the SBI, giving 33.1% (ABI No. 1242), 18.9% (ABI No. 1262), and 0% (SBI) autoclave survivors. Because the time needed to reach 134 degrees C (preconditioning time) increased as the day progressed, and varied from day to day, correlation between individual incremental heat exposure times and the number of surviving BI units was not possible. Standardized test conditions are necessary for a true comparison of BIs.

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Septicemia caused by anaerobic bacteria is indistinguishable from septicemia caused by aerobic bacteria. High age, origin in the gastrointestinal or genitourinary tract, malignancies and surgery or invasive, diagnostic procedures are indicative of anaerobic etiology. Between 5% and 15% of all septicemias are anaerobic. Benzylpenicillin is active against most anaerobic bacteria, and nitroimidazoles, clindamycin and chloramphenicol are dependable drugs in the treatment of bacteroides septicemias. Surgical drainage and debridement are of major importance, and proper measures to prevent circulatory failure are mandatory. Hyperbaric oxygen therapy may have a dramatic effect. The use of corticosteroids and endorphin antagonists is controversial. Exchange transfusions have been attempted, but further clinical trials are necessary to establish their place in the management of anaerobic septicemia.

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Following 400 mg brodimoprim given orally to 8 volunteers, the peaks of the mean concentration curves were 3.2 +/- 1.0 mg/l in serum and 1.0 +/- 0.2 mg/l (+/- SEM) in skin blister fluid. The terminal half-lives were 25.9 +/- 2.2 h and 42.2 +/- 6.5 h in serum and blister fluid, respectively. The area under the concentration-versus-time curve for blister fluid was 73% of serum value, and the mean recovery of bioactive drug in urine during 24 h was 3.4%. Considering the minimal inhibitory concentrations of potential target organisms and the slow elimination, the results suggest that brodimoprim may be useful in the treatment of infections, and that dosage once a day may be sufficient.

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Rat leukocytes were obtained from the peritoneal cavity by stimulation with potassium caseinate. The chemiluminescence response of the polymorphonuclear leukocytes exposed to opsonized zymosan was influenced by the interval between instillation of caseinate and harvesting of the cells. With intervals increasing from four to 72 hours, the maximum activity was reached after 24 hours. The myeloperoxidase activity of all the leukocytes together increased gradually up to 72 hours after instillation of caseinate. After exposure to zymosan particles, only a negligible fraction of this enzyme was released from the cells. On the other hand, the lysozyme activity was highest in cells harvested early, and a large fraction of this enzyme was also released from these cells. The findings emphasize the importance of standardized conditions for stimulation and harvesting of rat peritoneal leukocytes.

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Following 4 g of ceftriaxone, given intravenously, to eight volunteers, the antibiotic concentration in serum, suction skin blister fluid and fluid from subcutaneously implanted threads was followed for 28 h. High and sustained levels were found in both serum and extravascular fluids; the mean maximum serum concentration was 448 mg/l, and the mean peak concentrations in blister and thread fluid were 94 mg/l and 63 mg/l, respectively. The terminal, half-lives were: serum 7.2 h, blister fluid 10.3 h and thread fluid 11.3 h. The total area under the concentration versus time curves for serum was 1636 mg X h/l. For blister and thread fluid the areas were 1573 mg X h/l and 808 mg X h/l. The results suggest a twice daily dosage regimen.

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Granulocyte function was studied in 22 patients with untreated myelomatosis or macroglobulinaemia. Granulocyte adhesiveness (GA) and migration in capillary tubes (Tm) were, except for light chain disease, significantly decreased in patients of all gammopathy classes especially IgG myelomatosis. A plasma factor inhibited GA. The impairment of Tm was due to an inhibiting factor as well as lack of a stimulating plasma factor. Migration of granulocytes to skin chambers was decreased in patients with IgG myelomatosis. Chemiluminescence production during phagocytosis of opsonized zymosan was decreased. Compared to control sera, the opsonic activity of patient sera was strongly decreased. The impaired granulocyte functions in patients with malignant monoclonal gammopathy may contribute to the enhanced susceptibility to infections in these patients.

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Despite advances in antibiotic therapy, infection remains one of the major causes of death in compromised patients, and the severity of the underlying disease often determines the outcome of the infectious disease. During a 5-year period (July 1, 1974--June 30, 1979), septicaemia was diagnosed in 604 patients admitted to Haukeland Hospital, and 175 (29%) of these patients died. 640 septic episodes occurred in the 604 patients, and 684 bacterial strains were isolated from the blood. Staphylococcus aureus and Staphylococcus epidermidis accounted for 96 (14%) and 45 (6.6%) of the causative strains, respectively. 85 patients had septicaemia caused by S. aureus and 40 by S. epidermidis. 19 (22.4%) patients with S. aureus septicaemia and 9 (22.5%) with S. epidermidis septicaemia died. 12 of 21 (57%) patients with S. aureus or S. epidermidis septicaemia and underlying malignant disease died and only 16 of 104 (15%) patients with staphylococcal septicaemia and non-malignant disease. More than 96% of the S. aureus strains were susceptible to isoxazolylpenicillins, cephalothin, lincomycin or gentamicin, but only 18% to benzylpenicillin. The S. epidermidis strains were less susceptible to lincomycin and gentamicin. Single antibiotic treatment (a penicillin, cephalosporin or vancomycin) seemed as effective in staphylococcal septicaemia as combined penicillin/aminoglycoside therapy or other combinations. In compromised patients staphylococcal septicaemia is often fulminant, and antimicrobial therapy must be started as soon as specimens for microbiological cultures are obtained. So far, there is no clinical proof that antibiotic combination therapy is superior to single drug treatment. However, if penicillins can not be used or the response to single drug therapy is poor, combination therapy should be considered.

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Chemiluminescence (CL) production by polymorphonuclear leukocytes (PMNLs) was examined in 63 patients with bacterial infections and 63 healthy controls. The production was significantly higher in the patients (mean +/- standard error = 134.5 +/- 5.0 X 10(3) cpm) than in the controls (118.9 +/- 2.5 X 10(3) cpm; p less than 0.05). In 38 patients CL values were within the normal range and in 19 patients above. CL production below that of any control occurred in 6 patients: 3 (of 4) with staphylococcal endocarditis, 2 (of 4) with pneumococcal meningitis and 1 with salmonella septicaemia and osteomyelitis. PMNL hexose monophosphate shunt activity as measured by glucose metabolism correlated with CL production. Patients with low CL production more often had large numbers of juvenile and immature myeloid cells in the peripheral blood than patients with normal or high CL values. 3/6 patients with low CL values died, 2/38 with normal and 0/19 with high values. Directed and spontaneous PMNL migration was examined in 39 of the 63 patients with bacterial infections. 13 patients had PMNLs with higher directed and 16 with higher spontaneous migration capacity than their corresponding controls. The remaining patients had PMNLs with lower migration capacity. 2 of the 39 patients died. Each had PMNLs with low migration capacity. CL production by PMNLs was examined in 16 patients with viral infections and 16 healthy controls. The production was significantly lower in the patients (mean +/- standard error = 105.5 +/- 6.6 X 10(3) cpm) than in the controls (129.1 +/- 5.3 X 10(3) cpm; p less than 0.01). 15 patients had lower values than their corresponding controls. The PMNL migration capacity was also lower in the patients. These findings indicate that the majority of patients with bacterial infections have PMNLs with normal or increased function. However, some patients have reduced PMNL function and this reduction may contribute to a fatal outcome of the disease. Patients with viral infections usually have reduced PMNL function.

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In a double-filter modification of Boyden's method, formylmethionylleucylphenylalanine (FMLP) needed the presence of fresh plasma to induce leukocyte locomotor kinetics which compared with a model for directional migration. FMLP, or zymosan-activated plasma, did not stimulate migration in capillary tubes. The kinetics of leukocyte migration under agarose towards zymosan-activated plasma were more compatible to a model for increased random motility than for directional migration. Treatment of leukocytes with colchicin reduced their migration under gradient and non-gradient conditions in millipore filters, capillary tubes, and in under-agarose experiments.

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