In vitro comparison of cefoxitin, cefamandole, cephalexin, and cephalothin

The in vitro effect of cefoxitin, cefamandole, cephalexin, and cephalothin was tested against 645 strains of bacteria recently isolated from clinical sources. Against gram-positive organisms cephalothin and cefamandole were the most effective, generally being three- to fourfold more active than cephalexin or cefoxitin. Enterococci were not inhibited by less than 25 mug of any of the antibiotics per ml. Against Enterobacteriaceae, cefoxitin and cefamandole were the most active. An exception was the Enterobacter strains, against which cefoxitin was the least effective. None of the Pseudomonas aeruginosa strains were susceptible to 100 mug of any of the cephalosporins per ml. Cefamandole was the most active agent against Neisseria meningitidis and Neisseria gonorrhoeae. It was also the most effective agent against Haemophilus influenzae, even when taking into account a threefold inoculum effect.     

Antimicrobial activity of the new carbapenem biapenem compared to imipenem, meropenem and other broad-spectrum beta-lactam drugs

The in vitro activity of biapenem was compared to that of imipenem, meropenem and other broad-spectrum beta-lactams. A total of 716 isolates from recent cases of clinical septicemia and an additional 137 stock strains possessing known beta-lactamases or other well-characterized resistance mechanisms were tested. The minimal concentrations inhibiting 90% of strains (MIC90) of Enterobacteriaceae species were for biapenem 0.03 to 1 mg/l and for imipenem 0.25 to 2 mg/l. No member of the Enterobacteriaceae was found to be resistant to biapenem. Biapenem and meropenem were the most active drugs against Pseudomonas aeruginosa, with an MIC90 of 1 mg/l. Biapenem was more active than ceftazidime against most gram-negative and gram-positive bacteria tested. Biapenem was as potent as imipenem against anaerobic bacteria (including Bacteroides fragilis), with an MIC90 of 0.25 mg/l. High MICs of biapenem were demonstrated for Xanthomonas maltophilia, oxacillin-resistant Staphylococcus spp. and Enterococcus spp. These species have demonstrated resistance to other carbapenems and to most of the newer cephalosporins. The results of this study, coupled with previously documented favorable qualities of biapenem, endorse further investigation of this broad-spectrum antibacterial agent for clinical use.     

Demodex folliculorum and topical treatment: acaricidal action evaluated by standardized skin surface biopsy

Resistance to third-generation cephalosporins mediated by beta-lactamases is an increasing problem for clinical therapeutics. A wide range of Enterobacteriaceae produce these AmpC enzymes (Bush-Jacoby-Medeiros group 1), including Enterobacter spp., Citrobacter freundii, Morganella morganii, Providencia spp., and Serratia marcescens. Resistance via this mechanism has been shown to be statistically correlated with the use of some third-generation cephalosporins, and the infections caused by these stably derepressed enzyme-producing species seem to occur most frequently in the seriously ill. More recently the genes encoding this enzyme have been documented on plasmids capable of transfer into other species such as Klebsiella pneumoniae. Fourth-generation cephalosporins, with stability and low affinity for the Amp C beta-lactamases and the ability to penetrate rapidly into the periplasmic space of Gram-negative organisms, offer a viable alternative in the treatment of these infections or as empiric regimens. Furthermore, these compounds (example: cefpirome) possess greater potency against the frequently occurring Gram-positive cocci such as oxacillin-susceptible staphylococci and the streptococci (including some penicillin-resistant strains) as compared to previously used anti-pseudomonal cephalosporias, ceftazidime.     

Erythromycin, clarithromycin, and azithromycin: use of frequency distribution curves, scattergrams, and regression analyses to compare in vitro activities and describe cross-resistance

MICs of erythromycin, clarithromycin, and azithromycin for 852 recent clinical isolates were determined by broth microdilution methods. Frequency distribution curves, scattergrams, and regression analyses were used to compare in vitro activities and describe cross-resistance. Clarithromycin was the most active drug against Bacteroides spp. but the least active against Haemophilus influenzae. Azithromycin was most active against H. influenzae, Moraxella catarrhalis, Pasteurella multocida, and Fusobacterium spp. but the least active against Streptococcus spp. and Enterococcus spp. All three drugs had equivalent activities against Staphylococcus spp. and gram-positive anaerobes. None of the three drugs was particularly active against members of the family Enterobacteriaceae or nonfermentative gram-negative bacilli, although concentrations of 4 micrograms of azithromycin per ml inhibited some strains of the family Enterobacteriaceae (particularly Escherichia coli and Citrobacter diversus) and Acinetobacter baumannii. Although relative drug activities varied by organism, organisms relatively susceptible to one were relatively susceptible to all and organisms relatively resistant to one were relatively resistant to all; an exception was fusobacteria, which were usually susceptible only to azithromycin. Cross-susceptibility and cross-resistance were, therefore, the rule (except for Fusobacterium spp.), although the percentage of susceptible organisms could be varied considerably on the basis of the selection of breakpoints.     

Inducible amp C beta-lactamase producing gram-negative bacilli from blood stream infections: frequency, antimicrobial susceptibility, and molecular epidemiology in a national surveillance program (SCOPE)

A surveillance study of nosocomial blood stream infections [Surveillance and Control of Pathogens of Epidemiologic Importance (SCOPE)] was conducted during a 14-month period in 1995 to 1996 in approximately 50 American medical centers. Among the 4725 blood stream infections, the etiologic agent was Enterobacter spp. in 230, Citrobacter freundii in 24, and Serratia marcescens in 65. The vast majority of these isolates (89%) had been sent to the University of Iowa including 198 Enterobacter spp. (46 Enterobacter aerogenes, 141 Enterobacter cloacae, 11 other Enterobacter spp.), 23 C. freundii, and 62 S. marcescens. Because these species are capable of producing Amp C beta-lactamase, we examined their susceptibility to 12 broad-spectrum antimicrobial agents. The frequency of resistance to ceftazidime and the molecular epidemiology of ceftazidime-resistant strains was also examined. Among the Enterobacter spp. and C. freundii isolates, resistance to third generation cephalosporins (ceftazidime, ceftriaxone) and broad-spectrum semisynthetic penicillins (piperacillin), with or without an enzyme inhibitor (piperacillin/tazobactam), was high, e.g., 35 to 50%. The S. marcescens isolates were quite susceptible to all agents tested. Both imipenem and cefepime were active against virtually all isolates tested including 84 stably derepressed Amp C-producing ceftazidime-resistant strains of Enterobacter spp. and C. freundii. The overall rank order of activity for the six best agents against these Amp C-producing strains was: imipenem (100% susceptible) > amikacin = cefepime (98.6%) > ciprofloxacin = gentamicin = ofloxacin (93.6 to 94.0%). Molecular typing studies of ceftazidime-resistant E. cloacae using an automated ribotyping system, as well as pulsed-field gel electrophoresis, indicated that although clonal spread of a single strain occurred in some of the medical centers, most of the episodes of bacteremia were caused by patient-unique strains. Control of these resistant organisms will require attention to microbiologic recognition of phenotypes, to infection control practices, and to limiting the overuse of certain extended spectrum beta-lactams.     

In vitro antimicrobial activity of fluoroquinolones against clinical isolates obtained in 1989 and 1990

The in vitro activity of nine fluoroquinolones, enoxacin, norfloxacin, ofloxacin, ciprofloxacin, lomefloxacin, tosufloxacin, sparfloxacin, fleroxacin and levofloxacin, and two earlier quinolones, nalidixic acid and pipemidic acid, against 1,346 bacterial strains isolated clinically between 1989 and 1990, was evaluated by agar dilution method. The bacteria studied were Staphylococcus aureus (including methicillin-susceptible and -resistant strains), Staphylococcus epidermidis, Enterococcus species (including high-level gentamicin-resistant strains), Escherichia coli, Salmonella species, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens, Citrobacter spp., Pseudomonas aeruginosa, Pseudomonas cepacia, Acinetobacter baumannii, and Bacteroides fragilis. In contrast to the moderate to poor activity of two earlier quinolones, the fluoroquinolones acted well against most Enterobacteriaceae and A. baumannii. The minimum inhibitory concentrations for 90% of the drug strains (MIC90s) were < 1 microgram/mL against most tested species. Ciprofloxacin, tosufloxacin, sparfloxacin, and levofloxacin were more effective against multi-drug-resistant nosocomial pathogens. All fluoroquinolones assayed were very active against methicillin-susceptible S. aureus, with MIC90s < or = 1 microgram/mL. For methicillin-resistant strains, on the other hand, the MIC90s were > or = 4 micrograms/mL. There was no significant difference in fluoroquinolone susceptibility between methicillin-susceptible and -resistant S. epidermidis. Sparfloxacin, tosufloxacin, ciprofloxacin and levofloxacin were more active against enterococci. Most fluoroquinolones were relatively inactive against B. fragilis, with the exception of tosufloxacin, sparfloxacin and levofloxacin. The MIC90s of most quinolones assayed against K. pneumoniae, Citrobacter spp., E. cloacae, S. aureus and S. epidermidis were at least four-fold higher in our study. Therefore, it is important for physicians to use fluoroquinolones carefully so as to prevent or delay the emergence of resistant strains.     

Antimicrobial activity of RU-66647, a new ketolide

A new macrolide subclass called ketolides, possess a mode of action similar to the macrolide-lincosamide-streptogramin (MLS) compounds. Utilizing reference in vitro tests, the in vitro activity of RU-66647 (a ketolide) was compared to other MLS compounds against 376 Gram-positive organisms and over 400 representative strains of Gram-negative bacilli. The ketolide's spectrum was most similar to clindamycin and an earlier drug in the series (RU-64004 or RU-004) against staphylococci and streptococci. However, RU-66647 was more active than erythromycin and azithromycin against oxacillin-resistant Staphylococcus spp. and vancomycin-resistant enterococci. Ketolide activity was more potent than other MLS drugs against vancomycin-susceptible enterococci (MIC90, 0.25-4 micrograms/ml) and all streptococci (MICs, < or = 0.25 microgram/ml). Erythromycin-resistant (constitutive) strains were generally inhibited by < or = 2 micrograms RU-66647/ml (staphylococci, 31 to 36%; streptococci, 100%; enterococci, 72%). RU-66647 was active against Haemophilus influenzae (MIC90, 2 micrograms/ml), Moraxella catarrhalis (MIC90, 0.12 microgram/ml), and pathogenic Neisseria spp. (MIC90 0.5 microgram/ml). The ketolide failed to inhibit Enterobacteriaceae, nonfermentative Gram-negative bacilli, and Bacteriodes fragilis group strains. RU-66647 was observed to be a promising new compound directed toward some organisms resistant to other MLS-class drugs.     

Activity of cefamandole and other cephalosporins against aerobic and anaerobic bacteria

The activity of cefamandole was comparable to that of cephalothin, cefazolin, and cephaloridine against Staphylococcus aureus, Streptococcus pyogenes, and Diplococcus pneumoniae. In contrast, cefamandole was considerably more active than cephalothin, cefazolin, or cephaloridine against gram-negative facultative bacilli, including Haemophilus influenzae, the most striking disparities being noted with indole-positive Proteus and Enterobacter. Bacteroides fragilis was more susceptible to cefoxitin than to cefamandole or cefazolin (median minimal inhibitory concentration, approximately 8, 32, and 32 mug/ml, respectively); cephalothin exhibited still less activity against this species. The majority of other anaerobes were inhibited by relatively low concentrations of all four cephalosporins. The results indicate a potentially valuable role for cefamandole against facultative gram-negative bacilli, including H. influenzae, but no exceptional activity against anaerobes.     

In vitro and in vivo antibacterial activities of T-3761, a new quinolone derivative

T-3761, a new quinolone derivative, showed broad and potent antibacterial activity. Its MICs for 90% of the strains tested were 0.20 to 100 micrograms/ml against gram-positive bacteria, including members of the genera Staphylococcus, Streptococcus, and Enterococcus; 0.025 to 3.13 micrograms/ml against gram-negative bacteria, including members of the family Enterobacteriaceae and the genus Haemophilus; 0.05 to 50 micrograms/ml against glucose nonfermenters, including members of the genera Pseudomonas, Xanthomonas, Acinetobacter, Alcaligenes, and Moraxella; 0.025 micrograms/ml against Legionella spp.; and 6.25 to 25 micrograms/ml against anaerobes, including Bacteroides fragilis, Clostridium difficile, and Peptostreptococcus spp. The in vitro activity of T-3761 against these clinical isolates was comparable to or 2- to 32-fold greater than those of ofloxacin and norfloxacin and 2- to 16-fold less and 1- to 8-fold greater than those of ciprofloxacin and tosulfoxacin, respectively. When administered orally, T-3761 showed good efficacy in mice against systemic, pulmonary, and urinary tract infections with gram-positive and gram-negative bacteria, including quinolone-resistant Serratia marcescens and Pseudomonas aeruginosa. The in vivo activity of T-3761 was comparable to or greater than those of ofloxacin, ciprofloxacin, norfloxacin, and tosufloxacin against most infection models in mice. The activities of T-3761 were lower than those of tosufloxacin against gram-positive bacterial systemic and pulmonary infections in mice but not against infections with methicillin-resistant Staphylococcus aureus. The activities of T-3761 against systemic quinolone-resistant Serratia marcescens and Pseudomonas aeruginosa infections in mice were 2- to 14-fold greater than those of the reference agents.     

Myocardial ischemic tolerance following heat stress is abolished by ATP-sensitive potassium channel blockade

The purpose of this study was to compare the effect, both in vitro and in vivo, of cefepime with those of four other cephalosporins, namely ceftriaxone, cefotaxime, cefuroxime and cephalothin, against penicillin-resistant pneumococci. One hundred pneumococcal strains, 31 penicillin-susceptible, 30 penicillin-intermediate-resistant and 39 penicillin-resistant pneumococci, were used in MIC studies. Time-kill experiments were carried out for four strains. In the mouse peritonitis model, the dose that gave protection to 50% of mice challenged with a lethal dose of pneumococci (ED50) was determined for three pneumococci and five cephalosporins. The MICs of all five cephalosporins and penicillin correlated significantly with each other. In vitro, the most potent cephalosporins against pneumococci were cefotaxime, ceftriaxone and cefepime, followed by cefuroxime and cephalothin. In time-kill experiments, carried out for four pneumococci, no differences were found in the killing effect of these five cephalosporins in relation to MICs. In the mouse peritonitis model, there was no significant correlation between log(MIC) and log(ED50) for the five cephalosporins against three pneumococci (Spearman's rho = 0.39, P = 0.16). However, if the values for cefepime against the three pneumococci were excluded, there was a significant correlation for the remaining four cephalosporins (Spearman's rho = 0.62, P = 0.04). For all three pneumococci, the ED50s of cefepime were lower than expected from the MICs. It was not possible to explain this beneficial difference in the effect of cefepime in terms of in-vitro bactericidal activities, serum protein binding or pharmacodynamic parameters.     

Susceptibility of Campylobacter fetus subsp. jejuni to twenty-nine antimicrobial agents

The activity of 29 antimicrobial agents was tested against 95 strains of Campylobacter fetus subsp. jejuni isolated from human stools. Furazolidone and gentamycin were the most active agents. The tetracyclines, erythromycin, and chloramphenicol were very active against most of the strains, but with each antibiotic a few resistant strains were found. The penicillins were relatively inactive, and the cephalosporins tested were only active against occasional strains.     

Idiopathic swelling of the lower lip associated with topical anaesthesia. Report of three cases

Aim of the present study was to evaluate the effect of cefamandole, cefuroxime and cefoxitin on the level of gastrointestinal (GI) colonization by Candida albicans in humans. Twenty-eight adult patients received one of these three cephalosporins for 10 days, as treatment of infection, and were studied prospectively. Quantitative stool cultures for yeasts were performed immediately before, at the end, and 1 week after discontinuation of treatment. All three antibiotics caused an increase of the yeast concentration in the fecal flora. The increase caused by cefoxitin was the highest (2.5 log10 CFU/g of stool). Our results suggest that the cephalosporins tested cause minor increases of the colonization of the GI tract by C. albicans.     

Outpatient management of asthma during pregnancy

CS-834 is a prodrug of the carbapenem R-95867, developed by Sankyo Co., Ltd., Tokyo, Japan. To investigate the possibility that CS-834 may be the first carbapenem usable in an oral dosage form, its in vitro antibacterial activity (as R-95867) and in vivo antibacterial activity were compared with those of cefpodoxime proxetil, cefditoren pivoxil, cefdinir, ofloxacin, imipenem, and amoxicillin. R-95867 had high levels of activity against methicillin-susceptible staphylococci and streptococci, including penicillin-resistant Streptococcus pneumoniae, as well as Neisseria gonorrhoeae, Moraxella catarrhalis, the members of the family Enterobacteriaceae (with the exception of Serratia marcescens), Haemophilus influenzae, and Bordetella pertussis; for all these strains, the MICs at which 90% of tested strains are inhibited (MIC90s) were 1.0 microg/ml or less. Against methicillin-resistant staphylococci, enterococci, Serratia marcescens, Burkholderia cepacia, Stenotrophomonas maltophilia, and Acinetobacter calcoaceticus, R-95867 showed activity comparable to or slightly less than that of imipenem, with MIC90s ranging from 2 to >128 microg/ml. The in vivo efficacy of oral CS-834 against experimental mouse septicemia caused by gram-positive and gram-negative bacteria was better than that of comparative drugs. In murine respiratory infection models, the efficacy of CS-834 reflected not only its potent in vitro activity but also the high levels present in the lungs.     

In vitro and in vivo antibacterial activities of CS-834, a novel oral carbapenem

CS-834 is a novel oral carbapenem antibiotic. This compound is an ester-type prodrug of the active metabolite R-95867. The antibacterial activity of R-95867 was tested against 1,323 clinical isolates of 35 species and was compared with those of oral cephems, i.e., cefteram, cefpodoxime, cefdinir, and cefditoren, and that of a parenteral carbapenem, imipenem. R-95867 exhibited a broad spectrum of activity covering both gram-positive and -negative aerobes and anaerobes. Its activity was superior to those of the other compounds tested against most of the bacterial species tested. R-95867 showed potent antibacterial activity against clinically significant pathogens: methicillin-susceptible Staphylococcus aureus including ofloxacin-resistant strains, Streptococcus pneumoniae including penicillin-resistant strains, Clostridium perfringens, Neisseria spp., Moraxella catarrhalis, most members of the family Enterobacteriaceae, and Haemophilus influenzae (MIC at which 90% of strains are inhibited, < or =0.006 to 0.78 microg/ml). R-95867 was quite stable to hydrolysis by most of the beta-lactamases tested except the metallo-beta-lactamases from Stenotrophomonas maltophilia and Bacteroides fragilis. R-95867 showed potent bactericidal activity against S. aureus and Escherichia coli. Penicillin-binding proteins 1 and 4 of S. aureus and 1Bs, 2, 3, and 4 of E. coli had high affinities for R-95867. The in vivo efficacy of CS-834 was evaluated in murine systemic infections caused by 16 strains of gram-positive and -negative pathogens. The efficacy of CS-834 was in many cases superior to those of cefteram pivoxil, cefpodoxime proxetil, cefdinir, and cefditoren pivoxil, especially against infections caused by S. aureus, penicillin-resistant S. pneumoniae, E. coli, Citrobacter freundii, and Proteus vulgaris. Among the drugs tested, CS-834 showed the highest efficacy against experimental pneumonia in mice caused by penicillin-resistant S. pneumoniae.     

Prevalence and sensitivity to antibiotics of Enterobacteriaceae isolated from urinary cultures in some microbiology laboratories of a city in west Greece

The prevalence of Enterobacteriaceae from midstream urine samples from patients with community acquired urinary tract infections (UTI) of a town in SW Greece during one year period and their susceptibility to antibiotics were studied. The most frequently recovered pathogens were E. coli (77%), Proteus mirabilis (10%), Klebsiella spp (8.7%), Enterobacter spp (2.5%) and Citrobacter freundii (1.8%). E. coli were found more resistant to carbenicillin, the combination of amoxicillin/clavulanic acid and cotrimoxazole. Half of the strains were found resistant to more than one antibiotics. All strains were found sensitive to aminoglucosides, 2nd generation cephalosporines (except cefoxitin), 3rd generation cephalosporines, aztreonam and imipeneme. According to our results a statistically significant increase of the resistance to antibiotics at individuals over 45 years of age was noticed. The positivity of the samples was not correlated to prior antibiotic consumption and to the occupation of the participants or their residence.     

In vitro evaluation of activities of nitazoxanide and tizoxanide against anaerobes and aerobic organisms

The antibacterial activities of nitazoxanide and its main metabolite, tizoxanide, were tested against a broad range of bacteria, including anaerobes. Metronidazole, amoxicillin, amoxicillin-clavulanic acid, piperacillin, cefoxitin, imipenem, and clindamycin were used as positive controls. MICs were determined by reference agar dilution methods. The 241 anaerobes were all inhibited by nitazoxanide, with the MICs at which 90% of isolates are inhibited (MIC90S) being between 0.06 and 4 mg/liter with the exception of those for Propionibacterium species, for which the MIC90 was 16 mg/liter. The MIC90s of nitazoxanide were 0.5 mg/liter for the Bacteroides fragilis group (80 strains), 0.06 mg/liter for Clostridium difficile (21 strains), and 0.5 mg/liter for Clostridium perfringens (16 strains). Metronidazole showed a level of activity comparable to that of nitazoxanide except against Bifidobacterium species, against which it was poorly active, and Propionibacterium species, which were resistant to metronidazole. The other antibiotics showed various levels of activity against anaerobes, with imipenem along with nitazoxanide being the most active agents tested. Tizoxanide was less effective than nitazoxanide except against the B. fragilis group, against which its activity was similar to that of nitazoxanide. Under aerobic conditions, nitazoxanide demonstrated poor activity against members of the family Enterobacteriacae and Pseudomonas, Staphylococcus, and Enterococcus species. The same results were obtained when culture was performed under anaerobic conditions with the notable exception of the results against Staphylococcus aureus. The MICs of nitazoxanide were in the range of 2 to 4 mg/liter for 34 clinical isolates of S. aureus, 12 of which were methicillin resistant, while tizoxanide was not effective.     

Decreased nitrogen rates and irrigation effect on celery yield and internal quality

Sparfloxacin, a new orally administered fluoroquinolone, was tested against 14,182 clinical strains isolated (generally blood stream and respiratory tract cultures) at nearly 200 hospitals in the United States (USA) and Canada. Sparfloxacin activity was compared with 13 other compounds by Etest (AB BIODISK, Solna, Sweden), broth microdilution, or a standardized disk diffusion method. Using the Food and Drug Administration/product package insert MIC breakpoint for sparfloxacin susceptibility (< or = 0.5 microgram/ml), 94% of Streptococcus pneumoniae (2666 isolates) and 89% of the other streptococci (554 isolates) were susceptible. However, at < or = 1 microgram/ml (the breakpoint for all nonstreptococcal species) sparfloxacin susceptibility rates increased to 100% and 98%, respectively, for the two groups of streptococci. Only 50% and 65% of pneumococci were susceptible to ciprofloxacin (MIC90, 3 micrograms/ml) and penicillin (MIC90, 1.5 micrograms/ml), respectively. Although there were significant differences between regions in the USA in the frequency of penicillin-resistant pneumococcal strains, results indicate that the overall sparfloxacin MIC90 was uniformly at 0.5 microgram/ml. Nearly all (> or = 99%) Haemophilus species and Moraxella catarrhalis, including those harboring beta-lactamases, were susceptible to sparfloxacin, ciprofloxacin, and amoxicillin/clavulanic acid. Only cefprozil and macrolides demonstrated lower potency and spectrum against these two species. Sparfloxacin was active against oxacillin-susceptible Staphylococcus aureus (96 to 97%), Klebsiella spp. (95%), and other tested enteric bacilli (93%). Comparison between broth microdilution MIC and disk diffusion interpretive results for M. catarrhalis, Staphylococcus aureus, and the Enterobacteriaceae showed an absolute intermethod categorical agreement of > 95% using current sparfloxacin breakpoints, in contrast to those of cefpodoxime for S. aureus where a conspicuous discord (98% versus 59%) between methods was discovered. These results demonstrate that sparfloxacin possesses sufficient in vitro activity and spectrum versus pathogens that cause respiratory tract infections (indications), especially strains resistant to other drug classes such as the earlier fluoroquinolones, oral cephalosporins, macrolides, and amoxicillin/clavulanic acid. The sparfloxacin susceptibility breakpoint for streptococci may require modification (< or = 1 microgram/ml) based on the MIC population analysis presented here. A modal MIC (0.38 to 0.5 microgram/ml) was observed at the current breakpoint. Regardless, sparfloxacin inhibited 89% (nonpneumococcal Streptococcus spp.) to 100% (Haemophilus spp., M. catarrhalis) of the isolates tested with a median activity of 97% against indicated species.     

In vitro and in vivo antibacterial activities of ER-35786, a new antipseudomonal carbapenem

ER-35786 is a new parenteral 1 beta-methyl carbapenem with a broad antibacterial spectrum and a potent antipseudomonal activity. It showed high in vitro activity, comparable to those of meropenem and a new carbapenem, BO-2727, against methicillin-susceptible Staphylococcus aureus and streptococci, with MICs at which 90% of strains tested are inhibited (MIC90S) of < or = 0.39 microgram/ml. Against methicillin-resistant S. aureus, ER-35786 was the most active among the compounds tested, yet its MIC90 was 12.5 micrograms/ml. Against members of the family Enterobacteriaceae, Moraxella catarrhalis, and Haemophilus influenzae, ER-35786 inhibited 90% of strains tested at a concentration of < or = 1.56 micrograms/ml. The MIC90 of ER-35786 for Pseudomonas aeruginosa was 3.13 micrograms/ml, and the compound was more active than meropenem. In addition, the activity of ER-35786 against imipenem-, meropenem-, cefclidin-, or ceftazidime-resistant P. aeruginosa was equal to or higher than that of the most active reference compound. The in vivo activity of ER-35786 was consistent with this in vitro activity. The in vivo activity of ER-35786 was highest for systemic infection models with methicillin-resistant S. aureus and beta-lactam-resistant P. aeruginosa strains. In acute pneumonia caused by P. aeruginosa, ER-35786 produced a greater reduction in the viable cell count in the lungs than did imipenem-cilastatin or meropenem.     

N-formimidoyl-thienamycin: in vitro activity in bacteria with resistance to beta-lactam antibiotics or gentamicin

The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of N-formimidoyl-thienamycin were determined for 25 strains each of Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens and Pseudomonas aeruginosa which were resistant to gentamicin and/or acylureido penicillins or cefotaxime, cefoperazone or moxalactam, and for 38 strains of the group D streptococci. The drug was very active against the most frequently encountered gram-negative resistant causative organisms of nosocomial infections. The MIC ranged from 0.25-1 mg/l for multiresistant Enterobacteriaceae, and from 0.5-4 mg/l for multiresistant P. aeruginosa. The group D streptococci (enterococci) showed a low MIC (median: 0.75 mg/l); the median of the MBC was greater than 64 mg/l, however.     

Non-alcoholic steatohepatitis (NASH): a disease of emerging identity and importance

The agar dilution MIC method was used to test the activity of cefminox, a beta-lactamase-stable cephamycin, compared with those of cefoxitin, cefotetan, moxalactam, ceftizoxime, cefotiam, cefamandole, cefoperazone, clindamycin, and metronidazole against 357 anaerobes. Overall, cefminox was the most active beta-lactam, with an MIC at which 50% of isolates are inhibited (MIC50) of 1.0 microg/ml and an MIC90 of 16.0 microg/ml. Other beta-lactams were less active, with respective MIC50s and MIC90s of 2.0 and 64.0 microg/ml for cefoxitin, 2.0 and 128.0 microg/ml for cefotetan, 2.0 and 64.0 microg/ml for moxalactam, 4.0 and > 128.0 microg/ml for ceftizoxime, 16.0 and > 128.0 microg/ml for cefotiam, 8.0 and >128.0 microg/ml for cefamandole, and 4.0 and 128.0 microg/ml for cefoperazone. The clindamycin MIC50 and MIC90 were 0.5 and 8.0 microg/ml, respectively, and the metronidazole MIC50 and MIC90 were 1.0 and 4.0 microg/ml, respectively. Cefminox was especially active against Bacteroides fragilis (MIC90, 2.0 microg/ml), Bacteroides thetaiotaomicron (MIC90, 4.0 microg/ml), fusobacteria (MIC90, 1.0 microg/ml), peptostreptococci (MIC90, 2.0 microg/ml), and clostridia, including Clostridium difficile (MIC90, 2.0 microg/ml). Time-kill studies performed with six representative anaerobic species revealed that at the MIC all compounds except ceftizoxime were bactericidal (99.9% killing) against all strains after 48 h. At 24 h, only cefminox and cefoxitin at 4x the MIC and cefoperazone at 8x the MIC were bactericidal against all strains. After 12 h, at the MIC all compounds except moxalactam, ceftizoxime, cefotiam, cefamandole, clindamycin, and metronidazole gave 90% killing of all strains. After 3 h, cefminox at 2 x the MIC produced the most rapid effect, with 90% killing of all strains.