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PubMed1985

Antibacterial properties of carumonam (Ro 17-2301, AMA-1080), a new sulfonated monocyclic beta-lactam antibiotic.

The in vitro and in vivo activity of carumonam was tested in comparison with that of aztreonam and other beta-lactam antibiotics. With the exception of a few isolates that were overproducers of cephalosporinase, Enterobacteriaceae were highly susceptible to carumonam, 90% of the isolates being inhibited at 0.5 micrograms/ml. Aztreonam, ceftriaxone and ceftazidime were overall slightly less active than carumonam against Enterobacteriaceae. Carumonam was intermediate between ceftazidime and aztreonam as to the activity against Pseudomonas aeruginosa. Staphylococci were resistant to the monocyclic beta-lactams. In accordance with the in vitro data, carumonam was effective against experimental septicemias and infections of the thigh and the kidney that were caused by gram-negative pathogens.

Animals↗
PubMedDate not supplied

Comparative serum bactericidal activity against Pseudomonas aeruginosa of six antipseudomonal agents.

Serum levels and serum bactericidal activities of six antipseudomonal agents were studied comparatively in 60 patients. Single intravenous doses of gentamicin (1.5 mg/kg), piperacillin (4 g), ceftazidime (1 g), imipenem (0.5 g), aztreonam (1 g), and ciprofloxacin (200 mg) were given over 30 min to 10 patients each, and serum samples were obtained 30 min, 1, 2, 3, 4, 6, 8 and 12 h after beginning the infusion. Serum bactericidal activity was determined by the broth microdilution method against 10 recent isolates of Pseudomonas aeruginosa. Mean peak serum levels were as follows: gentamicin 10.4 micrograms/ml, piperacillin 227.5 micrograms/ml, ceftazidime 43.5 micrograms/ml, imipenem 17.3 micrograms/ml, aztreonam 42.3 micrograms/ml, and ciprofloxacin 3.9 micrograms/ml. All agents demonstrated effective serum bactericidal activity (geometric mean titer > 1:2) at peak serum levels. Ceftazidime was by far the most potent compound with a mean titer of 1:46.5, followed by ciprofloxacin (1:17), imipenem (1:13.7), and aztreonam (1:13.4). Ceftazidime also showed the longest duration of activity with a mean titer of 1:5.1 at 4 h. Based on our results, ceftazidime appeared to be the most potent antipseudomonal agent, while gentamicin and piperacillin were the least effective.

Anti-Bacterial Agents↗
PubMed1985

Temocillin. In vitro antibacterial activity.

Temocillin, a 6-alpha-methoxy penicillin derivative, was tested in vitro against 516 recent clinical isolates of Enterobacteriaceae. The compound exhibited good antibacterial activity, with 95% of isolates inhibited by a range 2 to 16 mg/L. Further studies, against selected isolates resistant to ticarcillin, piperacillin and cefuroxime (Klebsiella oxytoca, 25; Enterobacter species, 34; and Citrobacter species, 5), showed about half of the isolates of K. oxytoca (11/25) to be resistant to aztreonam (MIC range 16-greater than or equal to 128 mg/L), but susceptible to temocillin, cefotaxime and latamoxef. In general, the resistant strains of Enterobacter species tested were not susceptible to cefotaxime (MIC range 16-128 mg/L), or aztreonam (MIC range 1.0-64 mg/L), and many exhibited reduced susceptibility to latamoxef (MIC range 2-128 mg/L). In contrast, all the strains were susceptible to temocillin (MIC range 4-16 mg/L). The bactericidal activity of temocillin was confirmed against selected aztreonam-resistant strains of K. oxytoca and Enterobacter cloacae by conventional time-kill studies, and against a strain of E. cloacae in an in vitro model system designed to simulate the temocillin concentration profiles attained in extravascular fluid such as peripheral lymph. In the time-kill studies, temocillin concentrations of 16 and 32 mg/L were shown to effectively reduce the numbers of viable bacteria by 99 and 99.9%, respectively, within 12 hours. In the in vitro model system the numbers of bacteria were reduced 99.9% over the initial 4-hour period. In combination with aminoglycoside antibiotics, temocillin exerted a synergistic or partially synergistic effect (sigma FIC less than or equal to 0.75) against the majority of strains of Pseudomonas aeruginosa tested. When combined with piperacillin, cefotaxime or latamoxef, temocillin, unlike cefoxitin, exhibited no antagonism against strains of Enterobacteriaceae producing inducible cephalosporinases.

Anti-Bacterial Agents↗
PubMed1988

Evaluation of bactericidal activity of cefotaxime and other beta-lactams by a novel method.

In previous studies on Streptococcus faecium we proposed that the minimum beta-lactam concentration killing 99.9% of a bacterial population within 3 hours be defined as the minimum directly bactericidal concentration (MDBC) of that drug. In the present study we first evaluated the kinetics of cellular killing by various beta-lactams as related to penicillin-binding-protein (PBP) binding in Escherichia coli DC2, a hyperpermeable mutant. We concluded that in E. coli the MDBC for beta-lactams coincides with the minimum concentration capable of saturating PBPs 1b, 2 and 3. Of the antibacterial drugs we studied, cefsulodin, mecillinam and aztreonam had a much greater affinity for one essential PBP (PBP 1b, 2 and 3, respectively) than for all others, whereas cefotaxime had close affinities for all the above PBPs. MDBC values of greater than 500, 500, greater than 50, 10 and 1.5 mg/L were obtained for cefsulodin, mecillinam, aztreonam, ampicillin and cefotaxime, respectively. On the basis of the pharmacokinetic properties of these drugs, our results indicate that mecillinam, ampicillin and cefsulodin may be bactericidal in urine but not at other body sites; aztreonam is probably bactericidal in urine and blood, but not elsewhere; and cefotaxime is bactericidal in all the biological fluids we studied.

Amdinocillin↗
PubMedDate not supplied

Comparative activity of newer antibiotics against gram-negative bacilli.

The in vitro activities of cefoperazone, cefotaxime, ceftriaxone, ceftazidime, azlocillin, mezlocillin, piperacillin, ticarcillin/clavulanate, aztreonam, imipenem, and ciprofloxacin were concurrently determined against over 1,000 isolates of gram-negative bacilli from clinical specimens of patients at the Cleveland Clinic. Cephalosporins, penicillins, and aztreonam were active against species of Enterobacteriaceae other than Citrobacter freundii, Enterobacter aerogenes, and Enterobacter cloacae. Ceftazidime was the most active cephalosporin against Pseudomonas aeruginosa. Against the Enterobacteriaceae, the rank order of activity of penicillins was ticarcillin/clavulanate greater than piperacillin greater than mezlocillin greater than azlocillin. Against P. aeruginosa, the rank order of activity of penicillins was piperacillin greater than ticarcillin/clavulanate greater than azlocillin greater than mezlocillin. Aztreonam was less active v P. aeruginosa than ceftazidime, cefoperazone, or piperacillin. The most active antimicrobials against all isolates tested were imipenem and ciprofloxacin.

Aztreonam↗
PubMed1990

Synthesis and antimicrobial properties of substituted 3-aminoxypropionyl and 3-aminoxy-(E)-2-methoxyiminopropionyl monobactams.

The substituted 3-aminoxyproprionyl (VII) and 3-aminoxy-(E)-2-methoxyiminopropionyl monobactams (VIII) which possess the monocyclic beta-lactam nucleus of aztreonam (IX) were synthesized by reaction of triethylammonium (3S, 4S)-3-amino-4-methyl-2-oxo-1-azetidinsulfonate with the aminoxy acids X and XI, respectively. Compounds VII and VIII were assayed in vitro for their antimicrobial properties against Gram-positive and Gram-negative bacteria, whether producers of beta-lactamases or otherwise. Both types of compounds (VII and VIII) exhibited a poor antibacterial activity towards Gram-positive bacteria, comparable to that of aztreonam. On the contrary VII and VIII proved to be practically inactive against Gram-negative microorganisms, towards which aztreonam exhibits a high degree of activity.

Anti-Bacterial Agents↗
PubMed1989

In vitro activity of tigemonam against multiresistant nosocomial Enterobacteriaceae.

Tigemonam, an oral monobactam that exhibits beta-lactamase stability similar to that of aztreonam, was tested in vitro against 240 species of Enterobacteriaceae (50 Escherichia coli, 48 Klebsiella pneumoniae, 52 Enterobacter cloacae, 32 Proteus mirabilis, 22 Proteus indole-positive [Providencia sp.], 24 Serratia sp., and 12 Citrobacter sp. All strains were resistant to ampicillin and first-generation cephalosporins. In addition, 77.4% were resistant to amoxicillin plus clavulanic acid, 46.8% to cefuroxime, 23.3% to ceftriaxone, 22.2% to aztreonam, 46.9% to cotrimoxazole, and 0.9% to norfloxacin. Tigemonam at a concentration of 4 micrograms/mL or less inhibited 72.7% of the strains with minimum inhibitory concentrations ranging from 0.03 or less to more than 512 micrograms/mL. The highest intrinsic activity was observed against Proteus sp. Tigemonam proved to be a bactericidal antibiotic. Cross-resistance was chiefly observed with aztreonam and ceftriaxone. It is concluded that tigemonam should play an important role in the treatment of nosocomial infections that do not require parenteral therapy and in the treatment of multiresistant community-acquired infections.

Aztreonam↗
PubMed1988

Carumonam's in-vitro activity against gram-negative bacteria and its stability to their beta-lactamases.

The in vitro activity of the novel monobactam carumonam (RO17-2301) was evaluated on 311 gram-negative clinical isolates in comparison to aztreonam, cefotaxime, ceftazidime, cefotetan and ceftriaxone. Carumonam showed an antibacterial potency equal to or higher than any other reference compound; in particular it was the most effective against Proteus indole positive and Klebsiella sp. Its antipseudomonal activity was comparable to that of ceftazidime and it showed, together with aztreonam, the highest activity against the Citrobacter, Enterobacter and Escherichia coli isolates. The minimal inhibitory concentrations performed on permeability altered organisms indicated that carumonam has a penetration rate comparable to aztreonam and higher than cefotetan and ceftriaxone. Carumonam demonstrated excellent stability to chromosomal and plasmid-mediated beta-lactamases and that correlated with its antibacterial activity against the producing strains and inoculum size effect.

Anti-Bacterial Agents↗
PubMed1988

UTIs and two new antibiotics in the elderly.

Of the new antimicrobials available for the treatment of urinary tract infections (UTIs), aztreonam and imipenem/cilastatin represent two structurally unique, but distinct, classes of beta-lactam antibiotics. Aztreonam has a directed spectrum of activity covering gram-negative bacilli usually associated with UTIs. In comparative clinical trials of patients with complicated UTIs, aztreonam is well-tolerated and is as effective as conventional control regimens, including aminoglycosides. On the other hand, the antimicrobial spectrum of imipenem/cilastatin includes not only gram-negative bacilli but also gram-positive cocci and anaerobes. As such, this broad-spectrum antibiotic should be reserved for the treatment of mixed infections.

Aged↗
PubMed1993

Outer membrane proteins and lipopolysaccharide changes after exposure of Pseudomonas aeruginosa to antibacterial drugs.

Many studies show the low sensitivity of P. aeruginosa to antimicrobial agents, due to the permeability degree of the outer membrane (OM). Since the alterations of porins and lipopolysaccharides (LPS) are responsible for permeability to antibacterial drugs, the aim of this study was to evaluate the sub-M.I.C. effects of different antibiotics on the OM components. The M.I.C.s of five P. aeruginosa strains were determined and sub-M.I.C.s. versus PD-131,628, a new difluoroquinolone, aztreonam and netilmicin were calculated. The OM components were extracted before and after contact with the antibacterial drugs. We noted a decrease in M.I.C. values in two strains, and simultaneously an increase in the 19 and 38 Kd bands after using aztreonam. The M.I.C.s tended to increase in three strains after using netilmicin. The electrophoresis profile showed a decrease in the 38, 41 and 45 Kd bands and in one strain also in the 19 Kd band. The use of the quinolone did not significantly modify the M.I.C. values, although an evident increase in 38 and 41 Kd bands occurred in three strains. LPS alterations were observed with aztreonam and netilmicin, but not when PD 131,628 was used.

Anti-Bacterial Agents↗
PubMed2004

Double-disk synergy test positivity in Stenotrophomonas maltophilia clinical strains.

The double-disk synergy test (DDST) using Mueller-Hinton agar and antibiotic disks with centrally positioned disks of amoxicillin-clavulanate, ampicillin-sulbactam, and piperacillin-tazobactam and, at a center-to-center distance of 25-30 mm, 2-4 disks with 10 various beta-lactam antibiotics per one plate was performed in 58 clinical isolates of Stenotrophomonas maltophilia to determine the effectivity of 3 beta-lactamase inhibitors. When tested with clavulanate as the central beta-lactamase inhibitor synergic action on tested strains was the most frequent with aztreonam (81.0% of strains), cefoperazone (63.8%), and cefepime (60.3%). With sulbactam the synergic action, i.e. DDST positivity, was high in the case of cefoperazone (15.5%), ampicillin, aztreonam and piperacillin (8.6% each); with tazobactam it was the most frequent with aztreonam (53.4%), cefoperazone (44.8%) and cefepime (37.9%). No synergy was demonstrated after application of meropenem regardless of the kind of beta-lactamase inhibitor used. In 58 strains of S. maltophilia, 55 different profiles of DDST positivity were found. The results confirm that clavulanate is the most effective inhibitor of S. maltophilia beta-lactamases. The utilization of DDST (performed in the recommended way) for the typization of strains Stenotrophomonas species and for the estimation of potential effectiveness combinations of beta-lactams with beta-lactamase inhibitors for the therapy of stenotrophomonade infections was suggested.

Amoxicillin-Potassium Clavulanate Combination↗
PubMed1991

Novel transferable extended-spectrum beta-lactamase (SHV-6) from Klebsiella pneumoniae conferring selective resistance to ceftazidime.

A clinical isolate of Klebsiella pneumoniae sensu lato isolated from throat and a blood culture taken from a neutropenic patient treated for 2 weeks with ceftazidime and vancomycin was resistant to ceftazidime (MIC: 32 micrograms/ml) and moderately susceptible to aztreonam (MIC: 4 micrograms/ml). The isolate contained a plasmid of 180 kb which, when transferred to Escherichia coli by conjugation, conferred resistance to ceftazidime and tetracycline. The transconjugant had decreased susceptibility to ceftazidime (128-fold) and aztreonam (8-fold). Clavulanic acid and sulbactam each inhibited the resistance and clavulanic acid showed a synergistic effect when associated with ceftazidime and aztreonam. An extended-spectrum beta-lactamase with an isoelectric point of 7.6 was detected in the clinical isolates from blood and its transconjugant. This beta-lactamase showed similar substrate and inhibition profiles to SHV-1. In particular it did not hydrolyse ceftazidime. Hybridization with an intragenic probe for SHV-3 indicates that this beta-lactamase is an SHV-type enzyme. We propose that this novel CAZ-type extended-spectrum beta-lactamase be named SHV-6.

Ceftazidime↗
PubMedDate not supplied

Lomefloxacin (SC 47111 or NY-198), a new difluorinated quinolone: comparison of the in vitro activity with other broad spectrum antimicrobials against Enterobacteriaceae, Acinetobacter spp, Aeromonas spp, and Pseudomonas aeruginosa.

Using a broth microdilution method, we compared the in vitro activity of lomefloxacin to other broad spectrum antimicrobials against clinical strains of Enterobacteriaceae, Acinetobacter spp, Aeromonas spp, and P. aeruginosa. Against the Enterobacteriaceae and A. hydrophila, lomefloxacin showed excellent activity with MIC50 values ranging from 0.12-0.5 micrograms/ml and MIC90 values ranging from 0.12-1.0 micrograms/ml. By comparison, lomefloxacin had superior activity to nalidixic acid and difloxacin, comparable activity to norfloxacin and fleroxacin, and slightly less activity than ciprofloxacin. Lomefloxacin was also more active than imipenem, ceftazidime, aztreonam, ticarcillin/clavulanic acid (T-CA), and gentamicin. Lomefloxacin was less active (MIC90, 4 micrograms/ml) against Acinetobacter strains than Enterobacteriaceae strains. Against these same Acinetobacter strains, lomefloxacin was 8- to 64-fold more active than ceftazidime, aztreonam, T-CA, and gentamicin but slightly less active than imipenem. Lomefloxacin was 2- to 8-fold more active than fleroxacin, difloxacin, and nalidixic acid against strains of P. aeruginosa. However, lomefloxacin was less active than ciprofloxacin and norfloxacin. Lomefloxacin had comparable activity to imipenem but was 2- to 16-fold more active than ceftazidime, aztreonam, T-CA, and gentamicin. Thus, lomefloxacin demonstrated comparable activity to other fluorinated quinolones in that it possesses high active against clinical strains of Enterobacteriaceae and had good-to-moderate activity against most strains of Acinetobacter and P. aeruginosa.

4-Quinolones↗
PubMed2005

Reevaluation of Enterobacteriaceae MIC/disk diffusion zone diameter regression scattergrams for 9 beta-lactams: adjustments of breakpoints for strains producing extended spectrum beta-lactamases.

Validity of the current susceptibility breakpoint criteria for 9 beta-lactam antimicrobials and performance of proposed alternative breakpoints to improve prediction of clinical outcomes were analyzed by testing a contemporary collection of 350 Enterobacteriaceae, enriched for an overrepresentative collection of 70 (20.0%) strains producing extended-spectrum beta-lactamases (ESBLs). The majority of the strains were isolated from bloodstream infections (83.7% of the entire collection and 85.7% of the ESBL subset). The 9 beta-lactam antimicrobials analyzed were aztreonam, cefepime, cefotaxime, cefotetan, cefoxitin, ceftazidime, ceftriaxone, ceftizoxime, and cefuroxime. Reference broth microdilution MIC results were compared with those zone diameters obtained by the standardized disk diffusion test. The correlation coefficient (r) was acceptable for all antimicrobials, ranging from 0.87 (cefotetan) to 0.97 (aztreonam, cefotaxime, and ceftazidime). Using the current susceptible breakpoint criteria for Enterobacteriaceae, the intermethod categorical agreement ranged from 90.6% (cefotaxime) to 98.0% (ceftazidime). Very major (false-susceptible by disk test) and major errors (false-resistant) were nil (0.0%) for 6 of the 9 beta-lactams. Minor error rates ranged from only 0.9% (cefotetan) to 9.4% (cefotaxime). The proposed MIC breakpoint criteria (generally lower) adjusted to levels to accurately detect ESBL-producing strains and better predict clinical outcomes, also had acceptable intermethod concordance ranging from 90.6% (cefotetan) to 100.0% (ceftazidime). Remarkably, an improvement in the intermethod categorical agreement ranging from +1.7% to +8.3% was observed for 7 of the 9 antimicrobials, including the ESBL index or screening compounds (aztreonam, ceftazidime, cefotaxime, and ceftriaxone). No change in the breakpoint criteria, with removal of the intermediate category was tentatively proposed for cefoxitin and cefuroxime, resulting in an increase of the serious intermethod errors (very major and major), but the absolute intermethod agreement remained highly acceptable at 90.6% to 93.4%. Although the current breakpoint criteria remain acceptable in minimizing intermethod discords, the alternative susceptible breakpoint criteria proposed by combining pharmacokinetic/pharmacodynamic (PK/PD), microbiology MIC population analyses, and clinical success parameters possess improved intermethod agreement for the ESBL screening drugs and 5 other broad-spectrum beta-lactam compounds. The Clinical Laboratory Standards Institute (formerly, the National Committee for Clinical Laboratory Standards) should consider these changes to facilitate the detection of all Enterobacteriaceae with low PK/PD target attainment rates, therefore having the potential for suboptimal responses with usual therapeutic dosing.

Anti-Bacterial Agents↗
PubMed1997

Transferable antibiotic resistance in nosocomial Stenotrophomonas maltophilia strain.

Stenotrophomonas maltophilia (298/85) was isolated from the extensively inflamed conjunctiva of a neonate in a regional hospital in Ostrava, Czech Republic. It was resistant to all available antibiotics except cefepime and trimethoprim. The donor S. maltophilia strain 298/85 transferred carbenicillin and cephaloridine resistance determinants to recipient strains of Escherichia coli K-12 3110 rif+ and Proteus mirabilis P-38 rif+. All transconjugant colonies were co-resistant also to kanamycin, cefotaxime, and aztreonam. Active hydrolysis of imipenem in the original strain was inhibited by ethylene diamine tetra-acetic acid, and hydrolysis of cefotaxime and aztreonam in the original strain and in the E. coli K-12 transconjugant was inhibited by clavulanate. In contrast, ceftazidime was hydrolyzed by the original strain and was not inhibited by clavulanate, indicating a different character of the resistance to cefotaxime or aztreonam and ceftazidime.

Anti-Bacterial Agents↗
PubMed2002

Biochemical characterization of a novel extended-spectrum beta-lactamase from Pseudomonas aeruginosa 802.

Pseudomonas aeruginosa 802 was isolated at Rabta hospital in Tunis and was resistant to extended-spectrum cephalosporins and aztreonam. It produced a pI 7.6 extended-spectrum beta-lactamase (ESBL). The ESBL, named LBT 802, was purified to homogeneity by filtration on Sephadex G-75 followed by CM-Sepharose chromatography and high-performance liquid chromatography (HPLC) on a TSK-gel SP-5PW column. The LBT 802 enzyme had a molecular mass of 30 kDa. It showed a broad-substrate profile by hydrolyzing benzylpenicillin, ampicillin, cephalothin, cephaloridine, cefotaxime, ceftriaxone, and cefpirome but not ceftazidime, cefoxitin, imipenem, or aztreonam. The highest hydrolytic efficiency (Vmax/Km) was obtained for ampicillin, cephalothin, cephaloridine, and benzylpenicillin. Among extended-spectrum cephalosporins the best substrate was ceftriaxone followed by cefotaxime and cefpirome. LBT 802 activity was inhibited by clavulanic acid, sulbactam, imipenem, cefoxitin, and aztreonam. It showed its lowest Ki values for clavulanic acid, imipenem and sulbactam.

Anti-Bacterial Agents↗
PubMedDate not supplied

Recent developments in beta-lactamase research and their implications for the future.

beta-Lactamases, major determinants of bacterial resistance to beta-lactam antibiotics, can be classified into specific molecular classes following identification of active-site amino acid or nucleotide sequences. The use of gene probes for epidemiologic purposes is becoming commoner. A semiempirical classification scheme has been proposed using substrate profiles and inhibition by clavulanic acid and aztreonam as criteria. Class 1 cephalosporinases are potently inhibited by aztreonam but poorly inhibited by clavulanate, whereas class 2 penicillinases and broad-spectrum beta-lactamases have very poor affinities for aztreonam but are inhibited by clavulanic acid. Class 3 beta-lactamases include the metalloenzymes. Resistance to beta-lactam antibiotics can be related to many beta-lactamase-mediated phenomena, including increased frequency of beta-lactamase production in clinical isolates, wider distribution of beta-lactamase-mediating plasmids, production of multiple beta-lactamases, induction of chromosomal class 1 cephalosporinases, selection of depressed mutants for production of class 1 enzymes, leakage of beta-lactamase from gram-negative organisms, functions of penicillin-binding proteins as beta-lactamases, and identification of novel beta-lactamases.

Anti-Bacterial Agents↗
PubMed1985

Gram-negative bacilli resistant to third-generation cephalosporins: beta-lactamase characterization and susceptibility to Sch 34343.

We studied 192 recent clinical isolates, comprising six species of Gram-negative bacilli resistant either to cefotaxime or latamoxef (Moxalactam), from several hospitals. All isolates were resistant to several other third-generation cephalosporins or a monobactam. Two to five types of chromosomal beta-lactamases, as defined by isoelectric focusing, were readily identified in each species. Isolates of Citrobacter, Enterobacter and Serratia produced higher levels of chromosomal beta-lactamase than corresponding cefotaxime-susceptible strains. In addition, 20 of 57 produced one or two plasmid-determined beta-lactamases, TEM-1, OXA-2, or a novel enzyme, OHIO-1. The penem and carbapenem antibiotics, Sch 34343 and imipenem, were more active than cefotaxime, ceftazidime, ceftriaxone, latamoxef and aztreonam against isolates of Acinetobacter, Citrobacter, Ent. aerogenes, Ent. cloacae and Morganella, whereas imipenem, ceftazidime, and aztreonam were more active against Serratia isolates. The addition of plasmid-determined beta-lactamase increased resistance to piperacillin, cefoperazone and cefamandole but not to cefotaxime, ceftazidime, ceftriaxone, latamoxef, aztreonam, Sch 34343, or imipenem. Of 24 strains susceptible to aminoglycosides, none produced a plasmid-determined beta-lactamase, whereas 20 were found among the 33 strains resistant to aminoglycosides. Resistance of clinical isolates to newer beta-lactams appears to be due primarily to a high level of chromosomal cephalosporinase present without inducing agents. The plasmid-determined beta-lactamases, TEM-1 and OHIO-1, contributed little to resistance to most of the newer beta-lactams but were strongly associated with aminoglycoside resistance in these selected isolates. The greater in-vitro efficacy of the penem and carbapenem antibiotics, Sch 34343 and imipenem, against most of these isolates makes them promising candidates as first line agents against these pathogens.

Acinetobacter↗