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Summary Serum bactericidal activity (SBA) was studiedin vitro after intravenous administration of cefoperazone alone or in combination with mezlocillin or amikacin to human volunteers. One hour after the infusion, cefoperazone (2 g), cefoperazone + mezlocillin (5 g) and cefoperazone + amikacin (500 mg) achieved comparable activity againstEscherichia coli andKlebsiella pneumoniae (100% of the strains being killed by a 1:8 or greater dilution). The activity of the three regimens was also similar againstPseudomonas aeruginosa (87–96% of the sera had an SBA = 1:8) and somewhat less forStaphylococcus aureus (52–60% with SBA = 1:8). Six and ten hours after administration, the SBAs were much lower for all regimens; a small advantage for cefoperazone + mezlocillin againstK. pneumoniae could be shown in comparison to the other regimens.

Summary The results of three consecutive clinical trials on the therapy of anaerobic infections in cancer patients have been compared. The success rate with lamoxactam (94%) (6000 mg/d i. v.) was statistically different from that of doxycycline (63%) (300 mg/d per os) and tinidazole (61%) (1200 mg/d per os). Clindamycin (1200 mg/d per os), clindamycin (2700 mg/d i. v.) and cefoxitin (6000 mg/d i. v.) resulted in a favourable outcome in approximately 80% of the patients. Mixed aerobic and anaerobic infections had a similar response rate (80%). Even when the anaerobic pathogen was resistant to therapy, six of ten patients were cured. Surgical drainage played an important role, but was difficult to assess precisely.

Cefoperazone, a new broad-spectrum cephalosporin, was administered by continuous infusion or intermittent injection to 20 and 25 patients respectively with gram-negative bacillary septicemia most of whom had severe underlying disease. No difference was observed in the clinical response of the two groups. The overall rate of favourable response was 76 %. Of the 40 non-neutropenic patients treated three died of infection despite sensitivity of the organism, three improved temporarily and three died as the result of superinfection. Three of the five neutropenic patients treated failed to respond to cefoperazone therapy, despite adequate serum bactericidal activity. Tolerance to cefoperazone was satisfactory. Emergence of cefoperazone-resistant strains leading to relapse or superinfection was not a major cause of failure.

Polypropylene has been produced for over 35 years and has a wide variety of applications including industrial uses, food packaging and many domestic uses. As a high-molecular-weight polymer, polypropylene is considered chemically inert with little or no physiological or toxicological effects. Nevertheless, early epidemiological studies of polypropylene production workers and carpet manufacturing employees who use polypropylene reported a significant excess of colorectal cancer. In one study, five of the seven cases were diagnosed within a five-month period, and in the other study, five cases were diagnosed within an 18-month period. Recent updates of these two study populations have found no continuation of the excess of colorectal cancer, thereby indicating that the earlier observations on these two groups reflected the chance nature of a time-space cluster. Moreover, investigations of polypropylene production workers in the United States, Germany, Australia and the United Kingdom found no association with colorectal cancer. When the results of all studies of polypropylene production workers are pooled, the summary risk ratio for colorectal cancer is 1.37 (95% confidence interval 0.83-2.11). Taken together, the epidemiological evidence and the absence of toxicological data do not support a causal association between polypropylene and colorectal cancer.

In vitro synergism of trimethoprim plus amikacin and trimethoprim plus sisomicin against 66 gramnegative bacilli was studied by microtiter checkerboard dilution. Synergism was defined as an FIC or FBC index equal to or less than 0.5. Fifty-two percent of strains were inhibited and 65 % killed synergistically by the former combination, and 27% and 36% respectively by the latter combination (p<0.01). Serum bactericidal activity against 16 strains resistant to ampicillin and/or cephalothin was studied using serum from five volunteers one and six hours after intravenous administration of trimethoprim (160 mg), amikacin (250 mg) or the combination, and from six volunteers after administration of trimethoprim, tobramycin (1 mg/kg) or the combination. With trimethoprim and amikacin serum bactericidal titers ⩾ 1∶8 were found more frequently with the combination (77 of 80 samples) than with either drug alone (trimethoprim 19 of 80 samples, amikacin 60 of 80 samples, p<0.01). Trimethoprim plus amikacin may be useful in the treatment of infections with gram-negative rods resistant to cephalothin and ampicillin.

Timentin (ticarcillin plus clavulanic acid) plus amikacin was administered as an empirical regimen to 52 febrile granulocytopenic patients with cancer and appeared as effective as the other commonly recommended combinations of antimicrobial agents. A favourable response was observed in 61% of episodes with bacteraemia and in 83% of the episodes without bacteraemia. However, the efficacy in Grampositive bacteraemia was suboptimal and the emergence of superinfections caused by Gram-positive cocci may represent a clinical challenge.

The Working Party on Safety in Biotechnology of the European Federation of Biotechnology reported [Künzi M, et al. Safe Biotechnology (1) — General considerations. Appl Microbiol Biotechnol 21:1–6] on the classification of human pathogens and other microorganisms. It is proposed to relate the various risk classes of these organisms to the categories of physical containment for recombinant DNA (rDNA) organisms according to the OECD report [OECD Report (1986) “Recombinant DNA Safety Considerations”, Paris].

Serum bactericidal activity against 20 strains of Pseudomonas aeruginosa was studied in 10 volunteers after administration of imipenem (25 mg/kg), imipenem (25 mg/kg) plus amikacin (7.5 mg/kg), and ceftazidime (25 mg/kg) plus amikacin (7.5 mg/kg). Eight strains were susceptible and 12 were resistant to ticarcillin. Serum levels were measured microbiologically after 30 and 60 min and were, respectively, 97 and 46 micrograms/ml for imipenem given alone and 79 and 45 micrograms/ml for imipenem given with amikacin. Despite the very large dose of imipenem used, imipenem and imipenem plus amikacin appeared slightly less active than ceftazidime plus amikacin (P less than or equal to 0.1; Wilcoxon matched-pairs test), with respective median titers at 30 min of 1:128, 1:128, and 1:256 against ticarcillin-susceptible strains and 1:32, 1:32, and 1:64 against ticarcillin-resistant strains; however, more than 90% of the serum determinations, regardless of the regimen, had a serum bactericidal activity greater than or equal to 1:8. Amikacin significantly increased the rate of killing in serum of P. aeruginosa by imipenem. Imipenem plus amikacin appeared as effective as ceftazidime plus amikacin in reducing the viable counts of P. aeruginosa after 24 h of incubation.

Empirical therapy with cefoperazone was compared with cefoperazone plus amikacin in granulocytopenic and nongranulocytopenic febrile patients. In nonneutropenic patients the overall response rate to cefoperazone was 88%; 10 of 12 gram-negative bacteremic patients were cured. Cefoperazone plus amikacin resulted in an 88% overall response rate and cured 14 of 15 patients with bacteremia. In neutropenic patients the overall response rate was 77% with cefoperazone alone and 73% with cefoperazone plus amikacin; the cure rates for gram-negative bacteremias were 8 of 11 and 6 of 12 patients, respectively. Our findings support the concept of single-drug empirical therapy with cefoperazone in febrile cancer patients, whether granulocytopenic or not, especially when gram-negative bacteremias are predominantly caused by Escherichia coli or Klebsiella species. The issue of Pseudomonas spp. and other more resistant pathogens needs further assessment with a larger number of patients.

Teicoplanin was evaluated in 47 patients with severe infections, including 14 patients with bone infections, 11 patients with soft-tissue infections, 7 patients with endocarditis, 5 patients with pneumonia, 3 patients with septic thrombophlebitis, 3 patients with septicemia of unknown origin, and 4 patients with miscellaneous infections. Overall, bacteremia was documented in 24 patients. The pathogens isolated were 35 strains of Staphylococcus aureus (including 8 methicillin-resistant strains), 4 strains of Staphylococcus epidermidis, 4 strains of Streptococcus faecalis, 2 strains of Streptococcus pneumoniae, 5 strains of other streptococci, and 1 Micrococcus luteus strain. A total of 22 patients (46.8%) were clinically cured, 8 patients (17.0%) improved, 2 patients (4.3%) had relapses after initial improvement, and 15 patients (31.9%) failed to respond. The results were better in nonbacteremic patients (19 of 23 patients [82.6%] were cured or improved) than in patients with bacteremia (12 of 24 patients [50%] were cured or improved). Bacteriological cure occurred in 25 patients (53.2%), and superinfections were documented in 6 patients (12.8%). No major adverse effects were observed. We conclude that teicoplanin is a potentially effective and well-tolerated antimicrobial agent for therapy of nonbacteremic infections caused by gram-positive bacteria.

Sera of volunteers receiving ceftazidime (2 g) or amikacin (500 mg), alone or in combination, or cefoperazone (2, 4, or 6 g) or cefoperazone (2 g) with amikacin (500 mg) were evaluated for bactericidal activity against Klebsiella pneumoniae and Pseudomonas aeruginosa. Serum bactericidal activities were similar for ceftazidime and ceftazidime plus amikacin, but were definitely lower for amikacin alone. Against P. aeruginosa, a 6-g dose of cefoperazone resulted in a higher frequency of peak serum bactericidal activities greater than or equal to 1:8 than a 2-g dose of cefoperazone plus amikacin. Killing studies, performed in 1:8 diluted serum, demonstrated a higher killing rate for cefoperazone plus amikacin than for a 6-g dose of cefoperazone, the more resistant P. aeruginosa excepted. Emergence of resistance was found with a 2-g dose of cefoperazone for K. pneumoniae and with a 6-g dose of cefoperazone for P. aeruginosa, but not with cefoperazone plus amikacin.

Of 30 patients with predominantly anaerobic localized infections superimposed on chronic tissue damage related to trauma, ischemia, or tumor, 22 (73%) responded satisfactorily to moxalactam therapy. Moxalactam-resistant anaerobic pathogens emerged in two patients and were responsible for treatment failure. In six patients, two of whom also acquired resistant anaerobic pathogens, isolation of moxalactam-resistant aerobic pathogens increased during therapy.

To determine whether high doses of amikacin would prevent the development of resistance in clinical isolates, the serum bactericidal activity and killing rate of conventional and high doses of amikacin and piperacillin alone and in combination were measured in volunteer sera against a series of ten strains each ofEscherichia coli, Klebsiella pneumoniaeandPseudomonas aeruginosa.Amikacin serum levels were 24.9±6.0 mg/l 1 h after infusion of the 7.5 mg/kg dose and 44.8±5.0 mg/l after the two-fold dose. Median serum bactericidal titers for low dose piperacillin + amikacin were 1∶8–1∶64 and for high-dose piperacillin + amikacin 1∶16–1∶128. Both were satisfactory, except against piperacillin-resistantPseudomonas aeruginosa(median bactericidal titers ⩽ 1∶2), and both combinations had equivalent killing rates.

Summary Therapy with cefoperazone (4 g/day i. v.) was successful in 11 of 14 cases of gram-negative bacillary septicemia (78%). The three failures were related toBacteroides fragilis andAcinetobacter sp. infections, and to one episode of endocarditis caused byEscherichia coli. Minimal bactericidal concentrations of cefoperazone for the causative pathogens were similar to those of gentamicin. A serum bactericidal activity of greater than 1:8 was achieved in 11 of 12 patients one hour after the administration of cefoperazone. Continuous infusion of cefoperazone maintained the serum bactericidal activity at a constant value of greater than 1:8. The clinical results, however, were equally good with intermittent and continuous therapy. Side-effects were minor, rare and most likely not related to cefoperazone.

Serum bactericidal activity was determined against 10 strains each of Pseudomonas aeruginosaand Staphylococcus aureusin serum from volunteers 1 and 6 h after intravenous infusion of cefotaxime, tobramycin, and the combination; or of moxalactam, tobramycin, and the combination. High serum bactericidal activity against P. aeruginosawas found significantly more frequently with moxalactam plus tobramycin than with cefotaxime, moxalactam, and tobramycin alone or with cefotaxime plus tobramycin.

The Working Party on Safety in Biotechnology of the European Federation of Biotechnology has proposed a classification of microorganisms that cause diseases in plants. In this paper appropriate safety levels are proposed for these classes of microorganisms in order to ensure that research, development and industrial fermentation work with plant pathogens will limit the risk of outbreaks of diseases in crops that could result from work with such microorganisms when they are cultivated in laboratories, glasshouses and biotechnology installations.

Temocillin (BRL 17421) a new penicillin, was compared with cefazolin against 20 strains of Klebsiella. The in vitro minimal bactericidal concentration of cefazolin was twice as active as that of temocillin. Serum bactericidal levels obtained in volunteers treated with temocillin were consistently higher than those levels reached after the administration of cefazolin at the 6-h sampling.

The bactericidal activity of rifampin plus other antibiotics was examined with in vitro checkerboard dilutions against 15 strains of staphylococci, with time-kill studies, and with determinations of serum bactericidal activities (SBAs) in volunteers. In vitro synergism was found consistently only in inhibitory assays with rifampin plus minocycline. Time-kill studies with rifampin plus methicillin revealed enhanced killing at concentrations close to the MBC but reduced combined activity at higher concentrations. SBAs with rifampin, oxacillin, and the two drugs in combination were studied in three treatment regimens (regimen A: 2 g of oxacillin and 300mg of rifampin; regimen B: I g of oxacillin and 450 mg of rifampin; and regimen C: 3 g of oxacillin and 450 mg of rifampin). The SBA against methicillin-sensitive Staphylococcus aureus was significantly lower with the two drugs in combination than with oxacillin alone in regimen A but not in regimen B. In vitro synergy with rifampin plus other antibiotics was not frequent. At high concentrations, the bactericidal activity of oxacillin was reduced by rifampin, but killing activity may be enhanced at low concentrations of oxacillin.

Results of three consecutive clinical trials of therapy of anaerobic infections in cancer patients were compared, using doxycycline versus tinidazole, clindamycin versus cefoxitin and tinidazole versus tinidazole plus amikacin. Mixed aerobic and anaerobic infections had a similar response rate when treatment consisted of a specific anti-anaerobic drug as compared to a broader antimicrobial therapy directed against aerobic and anaerobic pathogens. Even when the anaerobic pathogen was resistant to therapy, many patients were cured. Surgical drainage played an important role, but was difficult to assess precisely.