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The in vitro activity of GR-20263, a new aminothiazolyl cephalosporin, was compared with the activities of other beta-lactam antibiotics by using 800 clinical bacterial isolates. GR-20263 was highly active (inhibition of 90% of the isolates between 0.03 and 1 microgram/ml) against the common Enterobacteriaceae and 5 to 20 times more active than cefuroxime, cefoxitin, and cephalothin. GR-20263 was three to six times less active than cefotaxime against Escherichia coli, Klebsiella pneumoniae, Salmonella, and Shigella, but three to four times more active than cefotaxime against Proteus vulgaris and Serratia marcescens. The activity of GR-20263 against Pseudomonas aeruginosa (with minimal inhibitory concentrations of 2 and 8 micrograms/ml for 90 and 100% of the isolates, respectively) was similar to that of tobramycin, 2 times that of cefsulodin, 5 times that of piperacillin, and 10 times that of cefotaxime. Against Haemophilus influenzae GR-20263 was three time more active than ampicillin. The beta-lactamase-producing strains were as susceptible to GR-20263 as the beta-lactamase-negative strains. GR-20263 was less active than cefotaxime and ampicillin against Staphylococcus aureus.

The in vitro activity of piperacillin (T-1220), a new semisynthetic derivative of aminobenzylpenicillin, was investigated. The majority of streptococci and pneumococci were inhibited by 0.12 micrograms/ml; the staphylococci and enterococci were inhibited by 2 micrograms/ml. Piperacillin was slightly more active against Neisseria and Haemophilus influenzae than was ampicillin. Piperacillin was active against all members of the Enterobacteriaceae including the Klebsiella, 58% of which were inhibited by 8 micrograms/ml. The activity of piperacillin was at least equivalent, but generally superior, to that of ampicillin or carbenicillin on species susceptible to these drugs. Most striking was its activity on Pseudomonas aeruginosa: 50% were inhibited by 2 micrograms/ml, and 83% were inhibited by 4 micrograms/ml. The minimum bactericidal concentrations were very close to the minimum inhibitory concentrations, and in most species only a slight inoculum effect was observed on the minimum bacterial values except for certain P. aeruginosa strains. A complete parallel resistance exists between piperacillin and ampicillin or carbenicillin. However, the clinical importance of this is largely mitigated by the intrinsically higher activity of piperacillin.

In vitro activities of eight beta-lactamase-stable cephalosporins, cefoxitin, cefuroxime, cefotaxime, moxalactam, SCE-1365, cefoperazone, ceftazidime, and cefsulodin, were compared against selected cephalothin-resistant or beta-lactamase-producing gram-negative bacilli or both. SCE-1365, cefotaxime, moxalactam, and ceftazidime had very similar activities against Enterobacteriaceae; SCE-1365 displayed the highest activity, and ceftazidime displayed the lowest activity. These four antibiotics were about 20 times more active than cefoperazone and 50 to 100 times more active than cefoxitin and cefuroxime. Against Pseudomonas aeruginosa and the other Pseudomonas species, ceftazidime showed the highest activity by far, followed by cefsulodin and cefoperazone. A close parallel resistance against P. aeruginosa isolates was observed between piperacillin on the one hand and cefoperazone and cefsulodin on the other.

The in vitro activity of N-formimidoyl thienamycin (N-f-thienamycin) was compared with the activities of other B-lactam antibiotics, using over 500 clinical bacterial isolates. N-f-Thienamycin inhibited 90% of the isolates of the common Enterobacteriaceae between 0.006 and 2 microgram/ml, regardless of their resistance to amoxicillin, ticarcillin, or cephalothin. It was, however, fourfold less active than moxalactam and ceftazidime and eightfold less active than cefotaxime. N-f-Thienamycin was nearly as active as ceftazidime against Pseudomonas aeruginosa (mean minimal inhibitory concentration, 3.0 microgram/ml) and eightfold more active than cefotaxime and moxalactam. In contrast to cefotaxime, moxalactam, and ceftazidime, N-f-thienamycin was highly active against enterococci (mean minimal inhibitory concentration, 1.3 microgram/ml) and staphylococci. The oxacillin-susceptible Staphylococcus aureus were inhibited between 0.03 and 0.12 microgram/ml, and the oxacillin-resistant S. aureus were inhibited between 0.12 and 2 microgram/ml. The high activity of N-f-thienamycin against both of the most important gram-positive and gram-negative organisms makes it a very promising new antibiotic.

The minimal inhibitory concentration (MIC) of Ro 13-9904 against 245 clinical isolates was determined by an agar dilution method. The activity of Ro 13-9904 against most Enterobacteriaceae was similar to that of cefotaxime; it was slightly more active than cefotaxime against Proteus mirabilis, Providencia species, and Serratia marcescens, but slightly less active against Klebsiella species. Ro 13-9904 was twofold more active than cefotaxime and threefold more active than ticarcillin against ticarcillin-susceptible Pseudomonas aeruginosa, with a mean MIC of 7.2 micrograms/ml; isolates highly resistant to ticarcillin were inhibited by a mean MIC of 17.2 micrograms/ml. Ro 13-9904 was fourfold more active than ampicillin against susceptible Haemophilus influenzae and was equally active against beta-lactamase-producing isolates. Ro 13-9904 was highly active against pneumococci and moderately active (MIC, 4 micrograms/ml) against Staphylococcus aureus isolates, whether they were susceptible or resistant to penicillin G. Oxacillin-resistant S. aureus and Streptococcus faecalis were completely resistant to Ro 13-9904 (MIC, greater than 128 micrograms/ml).

The pharmacokinetics of piperacillin were studied in a total of 26 Caucasian normal male volunteers. Single intramuscular doses of 0.5, 1.0, and 2.0 g were given to three groups, each containing eight volunteers. Mean peak serum concentrations of 4.9, 13.3, and 30.2 μg/ml were assayed at 30 to 50 min, and measurable levels were present up to 4, 6, and 8 h, respectively, after dosing. Single intravenous bolus doses of 1.0, 2.0, 4.0, and 6.0 g were given to four groups of five subjects, and mean serum concentrations of 70.7, 199.5, 330.7, and 451.8 μg/ml were measured at the end of the injections. The antibiotic had a mean terminal serum half-life of 60 to 80 min after the intramuscular doses and 36 to 63 min after intravenous administrations, depending on the dose. The apparent distribution volume was 20 to 24 liters/1.73 m2, and distribution volume at steady state was 16 to 19 liters/1.73 m2. Mean urinary recovery in 24 h was 74 to 89% for the intravenous doses and 57 to 59% for the intramuscular doses. The piperacillin-creatinine clearance ratios indicated that the proportion of renal excretion of piperacillin through tubular secretion was 56 to 73%, and this was confirmed by the renal clearance data from eight volunteers receiving probenecid treatment before the piperacillin dose. Probenecid (1 g given orally before administration of piperacillin) increased peak serum concentration by 30%, terminal serum half-life by 30%, and the area under the plasma concentration curve by 60%, and it decreased the apparent distribution volume by 20% and the renal clearance of the intramuscularly administered (1 g) antibiotic by 40%. Injections of piperacillin by both parenteral routes were well tolerated.

In an open prospective study, single oral doses of norfloxacin (800 mg) and thiamphenicol (2.5 g) were used to treat, respectively, 122 and 46 consecutive patients with uncomplicated gonorrhea. Neisseria gonorrhoeae was eradicated from 119 (97.5%) patients treated with norfloxacin and from 35 (76.0%) patients treated with thiamphenicol. Norfloxacin treatment failure was not related to drug resistance or to insufficient absorption of the drug. Thiamphenicol failure correlated with low in vitro susceptibility of the infecting strain. In a single oral dose of 800 mg, norfloxacin appeared to be an excellent alternative treatment regimen for uncomplicated gonorrhea in an area with a high prevalence of penicillin-resistant gonococci.

A severe epidemic of dysentery began late in 1979 in northeast Zaire and spread to Rwanda, Burundi, and Tanzania. The epidemic strain is a multiply resistant Shigella dysenteriae type 1, which acquired resistance against trimethoprim and more recently against nalidixic acid in the course of the epidemic. A comparative open trial in Rwandan adults with Shiga dysentery involved 18 patients treated with norfloxacin at 400 mg twice daily and 12 patients treated with nalidixic acid at 1 g three times daily for 5 days. All isolates showed in vitro susceptibility to both drugs. Though norfloxacin eliminated Shigella organisms from stools more rapidly than nalidixic acid, its clinical superiority did not reach the level of significance. Norfloxacin is a promising drug and is more effective than nalidixic acid in the treatment of multiresistant shigellosis.

The in vitro activity of teicoplanin, a new antibiotic related to vancomycin, was determined against 456 gram-positive cocci. The activity of teicoplanin in comparison with that of vancomycin was similar against staphylococci but 4 to 40 times higher against enterococci and beta-hemolytic and viridans streptococci. The single-dose pharmacokinetics of teicoplanin were studied in six healthy volunteers after administration of 3 and 6 mg/kg intravenously and of 3 mg/kg intramuscularly. The kinetic parameters after both intravenous doses were very similar. The curves for concentration in plasma for the 3- and 6-mg/kg intravenous doses showed a triexponential decline with elimination half-lives of 47.3 and 44.1 h, respectively. The percentages of the doses recovered in urine (0 to 102 h) were 43.2 and 44.1%, respectively. The areas under the plasma curves were dose related: 256.5 and 520.9 micrograms/h per ml, respectively. The bioavailability of teicoplanin after injection of 3 mg/kg intramuscularly was 90%, and the peak level was 7.1 micrograms/ml. The mean levels in plasma 24 h after the 3-mg/kg doses were 2.1 and 2.3 micrograms/ml, respectively, and the mean level in plasma 24 h after the 6-mg/kg intravenous dose was 4.2 micrograms/ml.

The pharmacokinetics of ceftazidime and moxalactam were compared after intravenous and intramuscular administration of single 1-g doses to eight healthy volunteers in a crossover study. The bioavailability of the antibiotics after administration by either route was almost complete. Both drugs had similar areas under the serum curves. Significant differences between ceftazidime and moxalactam were observed with respect to the apparent volume of distribution (18.4 and 24.1 liters, respectively), to the terminal half-life (1.6 versus 2.0 h), and to urinary recovery of the active compound (96 versus 79%). Ceftazidime was almost completely eliminated by renal excretion (greater than 96%), whereas about 20% of the moxalactam was eliminated by nonrenal mechanisms. The concentrations of ceftazidime and moxalactam in serum after a 1-g dose exceeded the concentrations required to inhibit 90% of the Enterobacteriaceae for about 8 and 10 h, respectively. The levels of ceftazidime and moxalactam in serum exceeded the 90% minimal inhibitory concentration of Pseudomonas aeruginosa for about 6 and 1 h, respectively.

The new in vitro activity of temocillin (BRL 17421), a new beta-lactamase-stable penicillin, was compared with those of other beta-lactam antibiotics for over 500 clinical bacterial isolates. Temocillin inhibited 94% of the Enterobacteriaceae organisms at concentrations of 0.5 to 8 microgram/ml, regardless of organisms resistance to ampicillin, ticarcillin, cefazolin, or combinations thereof. Most pseudomonas aeruginosa isolates and all staphylococci and streptococci tested were resistant to temocillin.

The MICs of erythromycins A, B, C, and D and some of their derivatives were determined against 21 gram-positive and 15 gram-negative microorganisms. Antibacterial activity was confined to gram-positive and very few gram-negative bacteria. Erythromycin B was somewhat less active than erythromycin A, and erythromycin C and D showed about half that activity or even less. Most other derivatives had negligible activity. Determination of potency by diffusion and turbidimetric assays were in line with MICs. The examination of the results of these assays, however, revealed that there are differences between the data of different laboratories, depending on the microorganisms and conditions used.

The absorption and excretion of equivalent doses of ampicillin, pivampicillin, and amoxycillin were compared in 10 healthy volunteers after administration of these antibiotics in a randomized triple crossover fashion. As recommended, ampicillin and amoxycillin were administered on an empty stomach, whereas pivampicillin was given with breakfast. The mean half-life times were nearly identical for all three antibiotics: 60.9 min for ampicillin; 58.4 min for pivampicillin; and 62.2 min for amoxycillin. The absorption of the drugs was evaluated according to the following three criteria: the mean peak serum levels; the “area under the curve”; and the percentage of recovery in urine. By these criteria, pivampicillin was the best-absorbed drug, with absorption 3.0 to 3.6 times higher than that of ampicillin and 1.2 to 1.5 times higher than that of amoxycillin, whereas the absorption of amoxycillin was 2.1 to 2.9 times higher than that of ampicillin.