Randomized, controlled, dose-range study of Ro 25-8315 given before and after a high-dose combination chemotherapy regimen in patients with metastatic or recurrent breast cancer patients.

PURPOSE: To evaluate the safety, pharmacokinetics, and efficacy of three different dose levels of pegylated granulocyte colony-stimulating factor (Ro 25-8315) on progenitor cell mobilization and hematologic recovery in cancer patients. PATIENTS AND METHODS: Breast cancer patients (n = 36) were randomly assigned to receive before (part I) and after (part II) chemotherapy either a single-dose injection of Ro 25-8315 (20 microg/kg, n = 9; 60 microg/kg, n = 9; 100 microg/kg, n = 10) or a standard daily dose of filgrastim (part I, 10 microg/kg/d; part II, 5 microg/kg/d) (control group, n = 8). RESULTS: Overall, Ro 25-8315 was well tolerated. In part I, more progenitor cell mobilization was observed with Ro 25-8315 100 microg/kg. The peak of circulating CD34(+) cells was obtained at day +5 in the four groups, and the absolute neutrophil count (ANC) returned to less than 20 x 10(9)/L by day +15. In part II, high levels of circulating CD34(+) cells (> 20 cells/microL) were obtained in all four groups. The chemotherapy-induced neutropenia (< 1 x 10(9)/L) was similar in the four groups. Ro 25-8315 100 microg/kg was more effective than filgrastim in reducing the number of patients with an ANC less than 0.5 x 10(9)/L on day +12 after chemotherapy. CONCLUSION: A single injection of Ro 25-8315 100 microg/kg might be the optimal dose for steady-state peripheral-blood progenitor cell mobilization. A single injection of 20, 60, or 100 microg/kg could be as efficient as daily administration of filgrastim to correct chemotherapy-induced cytopenia. The optimal dose of Ro 25-8315 should be determined according to the planned chemotherapy regimen.

Lenercept (p55 tumor necrosis factor receptor fusion protein) in severe sepsis and early septic shock: a randomized, double-blind, placebo-controlled, multicenter phase III trial with 1,342 patients.

OBJECTIVE: Phase III study to confirm a trend observed in a previous phase II study showing that a single dose of lenercept, human recombinant p55 tumor necrosis factor receptor-immunoglobulin G1 (TNFR55-IgG1) fusion protein, decreased mortality in patients with severe sepsis or early septic shock. DESIGN: Multicenter, double-blind, phase III, placebo-controlled, randomized study. SETTING: A total of 108 community and university-affiliated hospitals in the United States (60), Canada (6) and Europe (42). PATIENTS: A total of 1,342 patients were recruited who fulfilled the entry criteria within the 12-hr period preceding the study drug administration. INTERVENTION: After randomization, an intravenous dose of 0.125 mg/kg lenercept or placebo was given. The patient was monitored for up to 28 days, during which standard diagnostic, supportive, and therapeutic care was provided. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was 28-day all-cause mortality. Baseline characteristics were as follows: a total of 1,342 patients were randomized; 662 received lenercept and 680 received placebo. The mean age was 60.5 yrs (range, 17-96 yrs); 39% were female; 65% had medical admissions, 8% had scheduled surgical admissions, and 27% had unscheduled surgical admissions; 73% had severe sepsis without shock, and 27% had severe sepsis with early septic shock. Lenercept and placebo groups were similar at baseline with respect to demographic characteristics, simplified acute physiology score II-predicted mortality, profiles of clinical site of infection and microbiological documentation, number of dysfunctioning organs, and interleukin-6 (IL-6) plasma concentration. Lenercept pharmacokinetics were similar in severe sepsis and early septic shock patients. Tumor necrosis factor was bound in a stable manner to lenercept as reflected by the accumulation of total serum tumor necrosis factor alpha concentrations. There were 369 deaths, 177 on lenercept (27% mortality) and 192 on placebo (28% mortality). A one-sided Cochran-Armitage test, stratified by geographic region and baseline, predicted 28-day all-cause mortality (simplified acute physiology score II), gave a p value of .141 (one-sided). Lenercept treatment had no effect on incidence or resolution of organ dysfunctions. There was no evidence that lenercept was detrimental in the overall population. CONCLUSION: Lenercept had no significant effect on mortality in the study population.

Pharmacodynamics and pharmacokinetics of single doses of subcutaneous pegylated human G-CSF mutant (Ro 25-8315) in healthy volunteers: comparison with single and multiple daily doses of filgrastim.

Ro 25-8315 is produced by conjugation of rhG-CSF mutant with polyethylene glycol (PEG). The purpose of this study was to examine the pharmacodynamics and pharmacokinetics of Ro 25-8315 in comparison with Filgrastim (rhG-CSF). Subjects received single subcutaneous doses of Ro 25-8315 ranging from 10 to 150 microg/kg using a double-blind, randomized, placebo-controlled design. Filgrastim was administered as a single dose (5 or 10 microg/kg) and, following a 14-day washout period, daily for 7 days. Ro 25-8315 increased absolute neutrophil count (ANC) by 6- to 8-fold and CD34+ cell count more than 30-fold at the highest doses tested. Single doses (60-150 microg/kg) of Ro 25-8315 and multiple doses of Filgrastim had similar effects on ANC and CD34+, although Ro 25-8315 had a greater effect on CFU-GM. The pharmacokinetics of Ro 25-8315 were dose-dependent, with peak concentrations and area under the serum concentration-time curve (AUC) increasing 100-fold over the range of doses studied. Time to reach peak concentration (T(max)) and half-life of Ro 25-8315 averaged 20-30 hr at all doses, approximately three times longer than with Filgrastim. Adverse events were not serious and occurred with similar frequency with both products. Pegylation of rhG-CSF mutant results in more desirable pharmacokinetic properties and a longer duration of action with effective increases in ANC and measures of peripheral blood progenitor cell mobilization for at least 1 week.

Influence of oral glycopeptides on the fecal flora of human volunteers: selection of highly glycopeptide-resistant enterococci.

Changes in fecal flora were evaluated in 22 healthy volunteers administered oral vancomycin or teicoplanin in 1989-1991 in Belgium. Evaluation of 5 colonies per subject revealed no glycopeptide-resistant enterococci in the predominant flora before glycopeptide administration; however, large numbers (mostly Enterococcus faecium) emerged by the end of the study in 14 (64%) of the subjects. Pediococci and lactobacilli also increased in number. In 1992, 40 healthy volunteers and 33 cancer patients were evaluated by plating stool samples directly onto selective media containing vancomycin; low numbers of vancomycin-resistant enterococci (< 50 cfu/g) were found in 11 (28%) of the 40 and 4 (12%) of the 33 samples, respectively. DNA restriction fragment length polymorphism analysis showed that most isolates were different, but all contained vanA in Tn1546-like elements. These results indicate that vanA and Tn1546-like elements were common in Belgium as early as 1989 and that community-based individuals in that location likely form a major reservoir for glycopeptide-resistant enterococci.

Influence of strain, biomaterial, proteins, and oncostatic chemotherapy on Staphylococcus epidermidis adhesion to intravascular catheters in vitro.

Initial adhesion of four phenotypically different strains of Staphylococcus epidermidis to 16 silicone, polyurethane, or hydrophilic polyurethane catheters was assessed in vitro by a bacterial radiolabeling method. The effect of catheter exposure to plasma proteins, to an anticancer polychemotherapy (5-fluorouracil, doxorubicin, cyclophosphamide), or to both of them was determined. Bacterial adhesion on native catheters was dependent on the hydrophobicity of both bacteria and catheters. The four strains tested adhered preferentially to silicone catheters (p < 0.05); adhesion was moderate to polyurethane surfaces, whereas the least adhesion was obtained for hydrophilic polyurethane catheters. Adsorption of plasma proteins on the surface produced a marked decrease in adhesion on silicone (-66.2%; p < 0.001) and polyurethane (-32.8%; p < 0.01) catheters and a marked increase in adhesion on hydrophilic surfaces (+91.7%; p < 0.05). Chemotherapeutic treatment of the catheter produced a slight but not significant decrease in adhesion on silicone (-17.4%) and polyurethane (-19.8%) catheters and a marked increase in adhesion on hydrophilic polyurethanes (+148.2%; p < 0.001). The in vitro simulation of catheter use suggested that oncostatic drugs and plasma proteins play an important role in S. epidermidis adhesion to intravascular catheters. Overall, bacterial adhesion is lowest on hydrophilic polyurethane catheters before and after simulation of catheter use.

Evaluation of Rapid ATB Staph for 5-hour antimicrobial susceptibility testing of Staphylococcus aureus. Groupement pour le Dépistage, L'Etude et la Prévention des Infections Hospitalières-Groep ter Opsporing, Studie en Preventie van Infecties in de Ziekenhuizen.

The accuracy of Rapid ATB Staph (bioMérieux, La Balme-Les Grottes, France) for detection of oxacillin resistance and for detection susceptibility to 11 other antimicrobial agents in 553 and 519 Staphylococcus aureus isolates, respectively, was evaluated by comparing results with those produced by oxacillin agar screen and agar dilution methods, respectively. Further characterization of isolates with discrepant results for oxacillin testing was done by PCR detection of the nuc and mecA genes. By oxacillin agar screening, there were 307 oxacillin-resistant and 246 oxacillin-susceptible isolates. Rapid ATB results were obtained in 5 h for 515 (93.2%) of the isolates tested. Rapid ATB showed 97.0% sensitivity for detection of oxacillin resistance, confirmed by the presence of the mecA gene. After repeat testing of isolates flagged by the ATB software as possible errors, sensitivity increased to 99% for oxacillin-resistant isolates. Essential agreement with agar dilution testing for susceptibility to amoxicillin-clavulanic acid, gentamicin, erythromycin, clindamycin, and ciprofloxacin, as estimated by Youden's J statistic, was > 0.90. Subpopulations of isolates with significantly increased MICs of amikacin, rifampin, and minocycline, indicating borderline susceptibility, were detected by Rapid ATB and categorized as resistant. Rapid ATB Staph showed adequate accuracy for detection within 5 h of the oxacillin- and multiple-drug-resistant S. aureus isolates currently prevalent in Belgium.

A prospective, randomized study of pefloxacin versus teicoplanin in the treatment of gram-positive coccal infections in cancer patients: early termination due to emergence of resistance to fluoroquinolones.

A randomized prospective study comparing pefloxacin to teicoplanin in the treatment of gram-positive infections in cancer patients was prematurely terminated because of the emergence of pefloxacin resistance associated with oxacillin resistance in Staphylococcus aureus and coagulase-negative staphylococci. Among 56 patients evaluated for efficacy (26 pefloxacin and 30 teicoplanin) and infected with bacteria susceptible to both antibiotics, the clinical cure and eradication rates were similar for pefloxacin (80.5% and 77.3% respectively) and teicoplanin (66.6% and 52.2% respectively). The relapse rates (15% and 10% for pefloxacin and teicoplanin respectively) and the overall mortalities within 1 month (42% and 31%) were similar.

Early adhesion of bacteremic strains of Staphylococcus epidermidis to polystyrene: influence of hydrophobicity, slime production, plasma, albumin, fibrinogen, and fibronectin.

Twenty bacteremic strains of Staphylococcus epidermidis were characterized according to their hydrophobicity, their ability to produce slime, and their in vitro adhesion to polystyrene microtiter plates precoated or not with plasma proteins. Four strains of Staphylococcus aureus were also tested for adhesion. Slime production in S. epidermidis was not correlated with initial adhesion, whether measured qualitatively or by a quantitative method. Hydrophobicity (xylene:water partition) was well correlated with adhesion. Slime production, adhesion, and hydrophobicity were highly strain dependent among S. epidermidis organisms. For S. epidermidis, early adhesion was inhibited (10% to 98%) by albumin and fibronectin in all strains, by plasma (19 strains), and by fibrinogen (18 strains). Stimulation occurred for one strain with plasma and two strains with fibrinogen. In contrast, adhesion was inhibited by albumin and markedly stimulated (twofold to 14-fold) by plasma, fibrinogen, and fibronectin for the four strains of S. aureus. Early adhesion of S. epidermidis to polymer surface appears to depend mainly on hydrophobicity and is usually impaired by plasma proteins, albumin, fibrinogen and fibronectin; with a heterogeneous behavior among the different strains tested. Slime production would interpose secondarily, after the first attachment.

Salmonella infections in a cancer center.

Data concerning 40 patients hospitalized in a cancer center and Salmonella infection were analyzed. Hematological malignancy was present in 24 patients (60%) and solid tumor in 14 patients (35%). Among the predisposing factors, antineoplastic chemotherapy was the most frequent (60%) followed by antacid use (47.5%), corticosteroids (37.5%), granulocytopenia below 500 neutrophils/microliters (15%), surgery (10%) and splenectomy (2.5%). Bacteremia was the most frequent clinical syndrome accounting for 42.5% of the patients. Focal infection, enteritis and carrier state accounted for the remaining 30%, 20% and 7.5% respectively. Salmonella typhimurium and S. dublin represented 65% of the isolates, with clear association between serotype dublin and bacteremia. All S. dublin isolates were resistant to chloramphenicol. Among dublin and typhimurium serotypes, 20% the isolates were resistant to the traditional antibiotics used in salmonellosis (ampicillin, chloramphenicol, cotrimoxazole). All strains were susceptible in vitro to cephalosporins. The frequency of relapse was 15% and the overall mortality (within 30 days) attributed to Salmonella infection was 15%.

Pharmacokinetics of cefepime: a review.

The pharmacokinetic profile of cefepime following single and repeated i.v. or im administration was evaluated in healthy volunteers (n = 130), volunteers with renal failure (n = 42), elderly volunteers (n = 24), and in infected patients (n = 10). Following a 30 min iv infusion of between 250 and 2000 mg, the maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC) increased in proportion to the dose, indicative of linear kinetics. The Cmax ranged between 16.3 and 133 mg/L, with corresponding AUC values ranging between 34 and 263 mg.h/L. The elimination half-life (T1/2) was approximately 2 h and was dose-independent. Total clearance (Cltot) for all doses ranged between 122 and 136 mL/min. Renal clearance (Clren) varied between 96 and 116 mL/min, suggesting that cefepime is eliminated mainly by glomerular filtration. No probenecid studies have been performed. Urinary excretion was comparable at all dose levels, with the parent compound accounting for > 80% of the recovered dose (i.v. or im). Following single im doses of between 250 and 2000 mg, absorption was rapid and the Tmax was attained in 1-1.6 h. Values for Cmax and AUC increased in a dose-proportional manner. The T1/2 was approximately 2 h and independent of dose. The bioavailability following im administration of 2000 mg was 100%. No accumulation following multiple i.v. or im dosing over 10 days was observed. Binding to plasma proteins was 16%. The volume of distribution at steady-state (Vdss) varied between 18 and 22 L and was dose-independent. The pharmacokinetic profiles of cefepime following single and repeated doses suggest that twice-daily administration by either the i.v. or im route is adequate to treat most infections caused by susceptible bacteria.

Ex vivo pharmacodynamic study of piperacillin alone and in combination with tazobactam, compared with ticarcillin plus clavulanic acid.

Ten volunteers received piperacillin (4 g), piperacillin (4 g) plus tazobactam (0.5 g) (Tazocin), and ticarcillin (3 g) plus clavulanic acid (0.2 g) (Timentin) intravenously over 30 min in a cross-over blinded scheme. Blood samples were obtained 0.5 and 3 h after the end of infusion to measure by (high-pressure liquid chromatography) the concentration and bactericidal titers against 70 gram-negative bacilli. Serum time-kill curves were done against 35 strains to measure killing rates and area under the time-kill curve. Using the measure of serum bactericidal activity, ticarcillin-clavulanic acid and piperacillin-tazobactam were equally effective against Pseudomonas aeruginosa, Escherichia coli, Enterobacter cloacae, Serratia marcescens, and Bacteroides fragilis. Piperacillin-tazobactam was superior to ticarcillin-clavulanic acid against piperacillin-resistant Klebsiella pneumoniae (4 to 16 times) and S. marcescens (2 to 4 times). By using the area under the time-kill curve, piperacillin-tazobactam was equivalent to ticarcillin-clavulanic acid against piperacillin-susceptible strains; piperacillin-tazobactam was significantly more active than piperacillin against piperacillin-resistant strains and was more active than ticarcillin-clavulanic acid when the sample obtained 3 h after the end of infusion to volunteers was considered. Serum piperacillin concentrations (mean +/- standard error of the mean; in mg/liter) were 115 +/- 13 at 0.5 h and 7.4 +/- 1.4 at 3 h after the administration of piperacillin alone and 105.5 +/- 12.6 (0.5 h) and 7.7 +/- 1.6 after the administration of piperacillin-tazobactam. Serum tazobactam concentrations (in milligram per liter) were 13.1 +/- 1.4 at 0.5 h and 1.2 +/- 0.2 at 3 h. The piperacillin-tazobactam ratio was 8 +/- 0.3 at 0.5 h and 6.2 +/- 0.5 at 3 h. Piperacillin-tazobactam appears promising against beta-lactamase-producing gram-negative bacilli.

Anaerobic bacteremia in a cancer center.

Seventy-five episodes of clinically relevant anaerobic bacterial bacteremia observed in cancer patients were reviewed. Gastrointestinal (22.7%), hematological (22.7%) and female genital tract (18.6%) cancers were the most common underlying malignant diseases. Among 84 strains of strict anaerobic bacteria recovered in the 75 patients, gram-negative rods were isolated in 49 patients (58.3%), gram-positive rods in 29 patients (34.5%) and gram-positive cocci in 6 patients (8%). Bacteroides spp. and Clostridium spp. were the most frequent pathogens (85.7%). Twenty-one episodes of bacteremia were polymicrobial, aerobic gram-positive cocci being the most frequently associated pathogens. When identified, the primary sites were the gastrointestinal tract (40%), the female genital tract (17.3%), skin and soft tissue (14.6%), the oropharynx (12%) and the lower respiratory tract (6.7%). The source remained unknown in 7 cases (9.3%). The overall survival (evaluated 10 days after the occurrence of bacteremia) was 82.5%. There was no difference in mortality between patients with monomicrobial and polymicrobial bacteremia. Pulmonary complications were more frequent in patients with fatal outcome in comparison to patients who survived. The mortality rate of the patients adequately treated was 10.3% compared to 41% for the patients not treated or treated inadequately (P = 0.016, chi 2).

Preincubation of Haemophilus influenzae with subinhibitory concentrations of macrolides: influence on human neutrophil chemiluminescence.

Preincubation of Haemophilus influenzae with antibiotics may influence opsonophagocytosis as studied by chemiluminescence. Two strains of H. influenzae (strain 1 [type b] and strain 2 [uncapsulated]) were pretreated with erythromycin, roxithromycin, clarithromycin, and azithromycin for 1 h in Haemophilus test medium (the last 25 min was either without serum or with 10% fresh serum or 10% decomplemented serum). Human neutrophils were stimulated with a pretreated or control inoculum at four different bacterium/neutrophil ratios and tested for luminol chemiluminescence with an LKB luminometer. The results were normalized for bacterium/neutrophil ratio and compared by the two-sided Wilcoxon test. Pretreatment of bacteria with one-half of the MICs of erythromycin, clarithromycin, and roxithromycin produced nonsignificant (P > 0.05) increases in the chemiluminescence response (means of 23% for strain 1 and 4% for strain 2). Pretreatment with azithromycin at one-half of the MIC produced an increase in the chemiluminescence response induced by serum-opsonized strain 1 (320% +/- 36% [mean +/- standard error of the mean]) and strain 2 (107% +/- 20%) (P < 0.05). This increase was concentration dependent: for strain 1, 60% +/- 18% at one-fourth of the MIC to 440% +/- 41% at the MIC; for strain 2, 10% +/- 5% at one-fourth of the MIC to 300% +/- 20% at the MIC. For strain 1, the maximal increase with azithromycin pretreatment (at the MIC) required opsonization with fresh serum. Opsonization with decomplemented serum was associated with a 53% +/- 21% increase; this increase was 28% +/- 3% in the absence of serum. For strain 2, azithromycin reduced the lag phase of the chemiluminescence response induced by the absence of serum but did not alter the chemiluminescence response in the presence of decomplemented serum. A significant contribution of soluble factors in the enhanced response observed with bacteria preincubated with azithromycin was excluded. The increase of the chemiluminescence response with azithromycin pretreatment was probably due to improvement in complement-dependent opsonization for strain 1 and to improvement in both serum-independent and serum-dependent opsonization for strain 2.

Wound dressing in major head and neck cancer surgery: a prospective randomized study of gauze dressing vs sterile vaseline ointment.

A total of 207 patients were randomized in a prospective comparative study of standard gauze dressing vs sterile vaseline ointment. 179 patients were evaluable. All patients received antimicrobial prophylaxis. The two groups (86 standard and 93 vaseline) were comparable as far as age (mean, 57 yr; range, 21-84), genders (155 males/24 females), weight (mean, 66 kg; range, 40-69), type of surgery, previous or concomitant anticancer treatment. Severity of surgery was identical, as was the severity of cancer, in the two groups. Wound infection within 20 days of surgery occurred in 31.2% (29/93) of the vaseline group and 24.4% (21/86) in the standard group (NSS). Bacteremia occurred in three patients from the vaseline group and in four patients from the standard group. Bronchopneumonia occurred in 10 patients from the vaseline group and 14 patients in the standard group. The spectrum of microorganisms recovered was similar in the two groups. The need for antimicrobial treatment (empiric or for documented infections) within 20 days after surgery was 34.4% (32/93) in the vaseline group and 36.0% (31/86) in the standard group. The median delay to infection (range in days) in the vaseline group was 9 (5-15) for wound and 6 (1-12) for bronchopneumonia. For the standard group the corresponding delays were 8 (4-15) and 7 (2-19). Vaseline dressing was not associated with an increased risk of infection as compared to the standard gauze dressing.

Use of the quinolones in the prophylaxis and treatment of granulocytopenic immunocompromised cancer patients.

The potential use of the quinolones in the prophylaxis and treatment of febrile episodes in granulocytopenic patients is reviewed. Of 7 controlled prophylactic studies performed with quinolones, 2 were double-blind and placebo-controlled. The occurrence of fever and mortality due to infection was not reduced with quinolone prophylaxis, although the occurrence of Gram-negative bacteraemia was significantly reduced. The delay to first fever was occasionally increased, and this was associated with a reduction in the number of days with antimicrobial agents. No effect was observed on disseminated fungal infections with quinolone prophylaxis. Breakthrough bacteraemia and subsequent infections were due to resistant organisms, mainly Gram-positive organisms (streptococci, staphylococci). Tolerability and compliance were excellent and were occasionally better than with the classic regimen [nonabsorbable antibiotics and cotrimoxazole (trimethoprim/sulfamethoxazole)]. Six controlled studies dealing with empiric treatment with the quinolones were reviewed. Overall, the results suggested that monotherapy with ciprofloxacin may be used in patients with a good prognosis (short and less severe neutropenia, solid tumours, compliant patients). Combinations with broad spectrum penicillins, netilmicin or teicoplanin seem to be as effective as the classic regimens (a broad spectrum penicillin or cephalosporin plus aminoglycosides), although the number of patients was limited (n = 334). The response rate of Gram-positive bacteraemia was lower with quinolone-containing regimens except for a combination that included teicoplanin.

Prospective multicentric study of the etiology of 1051 bacteremic episodes in 782 cancer patients. CEMIC (French-Belgian Study Club of Infectious Diseases in Cancer).

A total of 1051 bacteremic episodes (782 patients) were prospectively recorded in 10 cancer centers (9 French, 1 Belgian), with: patient's age (mean 53, range 1-89 years), underlying cancer, neutropenia (< 1000 neutrophils/microliters; 233), signs and symptoms, type of i.v. line (percutaneous central: 534; peripheral: 228; central implanted: 304), treatment, blood culture system, number of positive blood culture bottles/total obtained, time to growth. Of all episodes, 23.2% occurred within 48 h of admission. The patients were receiving systemic antibiotics at sampling (on AB) in 34.6% of cases. The 1147 pathogens isolated (86 polymicrobial) were: E. coli (10.7%), Klebsiella-Enterobacter-Serratia (6.1%), other enterobacteriaceae (2.2%), Pseudomonas aeruginosa (4.8%), other nonfermenters (4.7%), coagulase-negative staphylococci (CNS, 40.8%), Staphylococcus aureus (9.9%), streptococci (5.4%), enterococci (2.2%), anaerobes (3.4%), yeasts (3.5%), and other bacteria (6.9%). The CDC (Centers for Disease Control) criteria (1988) were used to assess significance: group 1: pathogenic species (616 episodes; 59%); group 2: clinical signs and isolation of a "contaminant" species (47; 4.5%); group 3: as in group 2 with an i.v. line and empiric antibiotic treatment (181 episodes including 176 CNS; 17%); group 4: non-significant (207 episodes including 203 CNS; 20%). Groups 1-3, in which the episodes were considered to be significant (844 episodes; 80%) were compared with non-significant episodes (Fisher). Significant differences (P < or = 0.05) were seen in time to growth (median growth within 24 h vs 48 h), fever (86% vs 54%), chills (40% vs 3%), hypotension (10% vs 2%), septic shock (9% vs 1%), polymicrobial etiology (10% vs 0.5%), and initiation of empiric antibiotic treatment (71% vs 4%). Bacteremic episodes of CDC groups 1, 3 and 4 were further studied in episodes with a single isolate as a doubtful clinical significance (482 episodes) and episodes with > or = 2 bottles positive of probable clinical significance (569 episodes; 54%). In group 1 (218 doubtful, 398 probably significant episodes) significant differences were seen in chills (36% vs 52%), shock (7% vs 13%), polymicrobial (8% vs 17%), initiation of empiric antibiotic treatment (60% vs 72%); in group 3 (87 doubtful, 94 probably significant) in time to growth delay; in group 4 (177 doubtful, 30 probably significant) in proportion with implanted catheter (26% vs 52%), fever (62% vs 10%), and time to growth. This study confirms the predominant role of Gram-positive cocci in bacteremia occurring in cancer patients.

Bacteraemia caused by non-aeruginosa Pseudomonas species in a cancer centre.

Fifty-one episodes of bacteraemia due to Pseudomonas species other than Pseudomonas aeruginosa occurring between 1980 and 1990 in a Belgian cancer centre were reviewed. This corresponded to an incidence of 0.62/1000 admissions, or 1.5% of all bacteraemic episodes. Twenty-nine episodes, each with several positive blood culture sets were considered clinically significant, including six patients belonging to a well-documented outbreak of pseudobacteraemia with Xanthomonas maltophilia and associated with contaminated blood sampling tubes. The respiratory tract was the source in six (20.7%), an infected intravenous catheter in 10 (34.5%) and the source was unknown in seven (24.1%). Seven patients died from infection (24.1%). Twenty-three episodes with a single positive blood culture set were considered clinically not significant, although four of them were considered significant by the Centers for Disease Control (CDC) criteria because of the presence of symptoms and specific antibiotic treatment being administered. None of the patients with a single isolate died from infection despite the fact that 17 of 22 did not receive an effective antimicrobial agent. All isolates were susceptible to co-trimoxazole.

Antimicrobial prophylaxis for major head and neck surgery in cancer patients: sulbactam-ampicillin versus clindamycin-amikacin.

A total of 99 patients with head and neck cancer who were to undergo surgery were randomized in a prospective comparative study of sulbactam-ampicillin (1:2 ratio; four doses of 3 g of ampicillin and 1.5 g of sulbactam intravenously [i.v.] every 6 h) versus clindamycin (four doses of 600 mg i.v. every 6 h)-amikacin (two doses of 500 mg i.v. every 12 h) as prophylaxis starting at the induction of anesthesia. The two groups of evaluable patients (43 in the clindamycin-amikacin treatment group and 42 in the sulbactam-ampicillin treatment group) were comparable as far as age (mean, 57 years; range, 21 to 84 years), sex ratio (71 males, 28 females), weight (mean, 66 kg; range, 40 to 69 kg), indication for surgery (first surgery, 48 patients; recurrence, 37 patients), previous anticancer treatment (surgery, radiation therapy, chemotherapy), type of surgery, and stage of cancer. The overall infection rate (wound, bacteremia, and bronchopneumonia) within 20 days after surgery was 20 patients in each group. Wound infections occurred in 14 (33%) sulbactam-ampicillin-treated patients and 9 (21%) clindamycin-amikacin-treated patients (P = 0.19; not significant). The rates of bacteremia were 2 and 4%, respectively. The rates of bronchopneumonia were 14.3 and 23.2%, respectively (P was not significant). Most infections were polymicrobial, but strict anaerobes were recovered only from patients who received sulbactam-ampicillin. Antimicrobial treatment was required within 20 days after surgery for 42% of the sulbactam-ampicillin-treated patients and 44% of the clindamycin-amikacin-treated patients. By comparison with previous studies, we observed a decreased efficacy of antimicrobial prophylaxis in patients with head and neck cancer undergoing surgery because of the increased proportion of patients who were at very high risk for infection (extensive excision and plastic reconstruction in patients with recurrent stage III and IV cancers) and because of the longer duration of surgery.