A total of 434 clinical aerobic gram-negative bacillary isolates were tested against LY127935, a new 1-oxa cephalosporin, and compared with other cephalosporins, penicillins, and aminoglycosides by a broth microdilution technique. Cefotaxime (HR756), a new semisynthetic cephalosporin, and LY127935 were more active, and showed lower minimun inhibitory concentrations (rantes, -O.12 to 2.0 ,ug/ml), than cefamandole, cefoxitin, and cefazolin against Escherichia coli, Klebsiella spp., Enterobacter spp., Proteus mirabilis, indole-positive Proteus spp., Serratia marcescens, Providencia spp., and Citrobacter spp. Against P. aeruginosa, piperacillin, azlocillin, and mezlocillin were the most active betalactam agents; 64 ,ug/ml inhibited 99, 93, and 87%, of the isolates, respectively. LY127935 and cefotaxime at 16 ,ug/ml inhibited 71% of Pseudomonas isolates, whereas the aminoglycosides gentamicin, tobramycin, and amikacin at a concentration of 4 ,ug/ml inhibited 84, 88, and 93%, respectively. Minimum bactericidal concentrations were determined for all isolates and were generally the same as the minimum inhibitory concentrations.LY127935 is a new parenteral semisynthetic 1-oxa cephalosporin antibiotic which has been shown in preliminary in vitro testing to be highly active against gram-negative microorganisms including Pseudomonas aeruginosa and Enterobacteriaceae resistant to other cephalosporins and cephamycins (4). Determination of MICs. Minimum inhibitory concentrations (MICs) were determined by a microdilution technique as described by Barry (1). Antibiotic dilutions were prepared in Mueller-Hinton broth. With calibrated pipettes, 50 ,ul of each antibiotic dilution was transferred to each well of a U-shaped microtiter plate (Dynatech, Inc., Alexandria, Va.), with resulting final antibiotic concentrations ranging from 0.12 to 64 ug/ml.Organisms to be tested were picked from nutrient agar slants and suspended in 1 ml of Mueller-Hinton broth. After overnight incubation at 37°C, the cultures were adjusted to 10' colony-forming units per ml with a 0.5 McFarland standard and then diluted 1:1,000 with Mueller-Hinton broth. A 0.05-ml amount of the culture dilution was added to each well of the microtiter plate, resulting in a final inoculum of 5 x 104 colony-forming units per ml.The microtiter plates were incubated for 18 h 864 on May 9, 2018 by guest http://aac.asm.org/ Downloaded from

A prospective, randomized, single-blind comparison of parenteral cefamandole and ampicillin was conducted in 27 hospitalized adult patients with pneumonia or purulent tracheobronchitis due to Haemophilus spp. Patients received either parenteral cefamandole or ampicillin in a dose of 1 g every 6 h. Cefamandole was as effective and safe as ampicillin. Of the 14 patients treated with cefamandole, 13 were considered cured, as were 12 of the 13 treated with ampicillin. One patient in each treatment group improved clinically but did not clear his sputum of Haemophilus spp. One patient treated with cefamandole had a recurrence of Haemophilus spp. bronchitis 9 days after cure. Adverse effects were more common in the cefamandole-treated group (50% versus 15%), but were mild and did not require discontinuation of therapy in any patient. The in vitro susceptibilities of 64 clinical isolates of Haemophilus spp. to 10 antibiotics were determined.Cefamandole was the most active of the cephalosporin-cephamycin antibiotics tested, inhibiting 98% of 61 non-beta-lactamase-producing isolates at 2 ,ug/ml and 100% at 4 ,g/ml. Cefamandole inhibited the three ampicillin-resistant isolates at 2 ug/ml or less. Cephapirin, cefoxitin, and cephalothin were the next most active, whereas cefazolin and cephradine were the least active.Ampicillin has generally been regarded as the antimicrobial agent of choice for Haemophilus influenzae bronchopulmonary infections (13). However, there have been recent reports of ampicillin-resistant H. influenzae strains, particularly type B (10,12,20,23). Recently, there have also been sporadic reports of resistance to chloramphenicol and tetracycline (14,23), the usual alternative drugs. Cefamandole, a new cephalosporin with a broad spectrum of activity, has been shown to be effective against various infectious disorders caused by H. influenzae (2,18

The concentration of spectinomycin in serum and cerebrospinal fluid was compared in rabbits with and without experimental pneumococcal meningitis. When injected intravenously, spectinomycin could not be detected in the cerebrospinal fluid of normal rabbits. In rabbits with meningeal inflammation, however, spectinomycin penetrated the blood-brain barrier and produced significant cerebrospinal fluid concentrations, equal to or well above spectinomycin minimal inhibitory concentrations for many bacterial species.Although spectinomycin is currently used primarily for treating infections with strains of Neisseriagonorrhoeae resistant to penicillin (5), this aminocyclitol is active in vitro against a variety of gram-positive and gram-negative bacteria (4, 8) at concentrations that persist in serum for 8 h or longer after intramuscular delivery of 2-to 4-g doses (2, 7). The broad-spectrum activity of spectinomycin might be exploitable in the treatment of meningitis, provided that the compound crossed the blood-brain barrier. The present study in rabbits with pneumococcal meningitis was designed to examine this possibility.A strain of type HI pneumococcus, isolated from a child with meningitis, was grown overnight in brain heart infusion broth (BBL, Microbiology Systems), and the suspension was adjusted to 108 colony-forming units per ml by using a 0.5 McFarland standard.New Zealand white rabbits weighing 2.5 to 3.5 kg were anesthesized with ketamine (30 mg/kg), acepromazine (3 mg/kg), and scopalamine (0.15 mg/kg), given together as a single intramuscular injection. With a 25-gauge needle, 0.5 to 1.0 ml of cerebrospinal fluid (CSF) was removed from the cisterna magna, and 0.5 ml of a pneumococcal suspension (5 x 107 colorny-forming units per ml) in brain heart infusion broth was injected intracistemally.Rabbits were studied when they developed signs of meningitis with lethargy and fever 12 to 24 h after intracisternal inoculation. A total of 21 rabbits with evidence ofmeningitis were given spectinomycin (60 mg/kg) intravenously over 1 min. CSF (0.5 to 1.0 ml) via cisternal puncture and heart blood were obtained at 15, 30, 60, 120, and 480 min after the intravenous injection of spectinomycin. Cell counts were performed on all CSF samples; those samples containing more than 30,000 erythrocytes per mm3 were considered to be significantly contaminated by blood and were not included in the study.Serum and CSF samples were assayed by a cup-plate method described by Bennett et al.(1). The assay organism was Escherichia coli (UC 527), and the medium was sterile streptomycin assay agar with yeast extract (antibiotic medium no. 5; BBL). On the day of each study, spectinomycin hydrochloride standards of 320, 160, 80, 40, 20, 10, 5, and 2.5 ,ug/ml were made up in sterile saline and pooled rabbit serum for use in the CSF and serum samples, respectively. The 5-ytg/ml standard produced the minimum readable zone. Each assay was run in duplicate, and the CSF and serum concentrations were calculated from a standard curve.Spectinomycin c...