Emergence of quinolone resistance among clinical isolates of methicillin-resistant Staphylococcus aureus in Ontario, Canada.

One hundred two isolates of methicillin-resistant Staphylococcus aureus (MRSA) randomly selected from across the Canadian province of Ontario were tested for their susceptibility to ciprofloxacin, norfloxacin, and nalidixic acid by the agar dilution method. Forty-nine percent (50 of 102) had high levels of resistance to these quinolone compounds. For the 50 resistant isolates, ciprofloxacin and norfloxacin had high MICs for 90% of isolates (MIC90s) of 128 micrograms/ml and greater than 128 microgram/ml, respectively; for these isolates, the nalidixic acid MIC90 was greater than 640 micrograms/ml. The majority (98%) of the 50 isolates were also resistant to tobramycin (MIC90, greater than 128 micrograms/ml), while 42% of the isolates were resistant to gentamicin (MIC90, 64 micrograms/ml). Quinolone-resistant MRSA isolates were susceptible to bacteriophages from several groups, indicating independent selection of resistant strains. These results suggest that a reappraisal of the use of fluoroquinolones against MRSA in Canada is necessary.     

In vitro activities of 12 orally administered antimicrobial agents against four species of bacterial respiratory pathogens from U.S. Medical Centers in 1992 and 1993.

Clinical isolates of Haemophilus influenzae, Streptococcus pneumoniae, Streptococcus pyogenes, and Moraxella catarrhalis were gathered from 19 different clinical laboratories throughout the continental United States. The in vitro activities of 12 orally administered antimicrobial agents were compared by broth microdilution tests with 3,151 bacterial isolates. Among 890 H. influenzae isolates, 30% were capable of producing beta-lactamase enzymes (12 to 41% in different medical centers). Most of the 619 beta-lactamase-negative H. influenzae strains were susceptible to ampicillicin (MIC, < or = 1.0 micrograms/ml): 5 strains were intermediate in susceptibility (MIC, 2.0 micrograms/ml) and 1 strain was ampilicillin resistant (MIC, 4.0 micrograms/ml). Ninety-two percent of 698 M. catarrhalis strains were beta-lactamase positive. Of 799 S. pneumoniae isolates, 15% were intermediate in susceptibility to penicillin and 7% were resistant to penicillin. The prevalence of penicillin-susceptible pneumococci in different institutions ranged from 63 to 95%. Only 1% of 764 S. pyogenes isolates were resistant to the macrolides, but 5% of S. pneumoniae isolates were macrolide resistant. Only 71% of 58 penicillin-resistant S. pneumoniae isolates were erythromycin susceptible, whereas 97% of the 622 penicillin-susceptible strains were erythromycin susceptible. Penicillin-resistant pneumococci were also relatively resistant to the cephalosporins and amoxicillin. Penicillin-susceptible pneumococci were susceptible to amoxicillin-clavulanic acid (MIC for 90% of isolates tested [MIC90], < or = 0.12/0.06 microgram/ml), cefixime (MIC90, 0.25 microgram/ml), cefuroxime axetil (MIC90, < or = 0.5 microgram/ml), cefprozil (MIC90, < or = 0.5 micrograms/ml), cefaclor (MIC90, 0.5 microgram/ml), and loracarbef (MIC90, 1.0 microgram/ml). Most strains of the other species remained susceptible to the study drugs other than amoxicillin.     

Antimicrobial susceptibility of clinical isolates of Brucella

A number of antimicrobial agents have been used in the treatment of human brucellosis with varying effectiveness. The purpose of this study was to test the in vitro susceptibility of isolates of four Brucella species to a variety of antimicrobial agents, and to study in vitro synergy of combinations of agents. Minimal inhibitory concentrations (MICs) were determined using conventional broth microdilution methods and commercially available systems. Conventional checkerboard synergy microdilutions were prepared for gentamicin or streptomycin plus tetracycline, and rifampicin plus tetracycline. Synergy or antagonism was determined by the fractional inhibitory concentration index. Penicillin G and ampicillin showed in vitro activity against Brucella (MIC90 4 micrograms/ml), whereas the antipseudomonal penicillins were less active (carbenicillin MIC90 12 micrograms/ml, piperacillin MIC90 32 micrograms/ml). Among the third generation cephalosporins tested, cefotaxime (MIC90 2 micrograms/ml) demonstrated greatest activity. As a class, aminoglycosides were equivalent (MIC90 1-4 micrograms/ml). All strains were sensitive to tetracycline (MIC90 0.25 microgram/ml), trimethoprim-sulfamethoxazole (MIC90 1/19 micrograms/ml), and rifampin (MIC90 1 microgram/ml). Erythromycin (MIC90 greater than 8 micrograms/ml) and vancomycin (MIC90 greater than 16 micrograms/ml) demonstrated no activity. In vitro synergy (fractional inhibitory concentration index less than 0.5) was demonstrated with tetracycline plus rafampin in six of eight isolates tested.     

In vitro antimicrobial activity of CP-99,219, a novel azabicyclo-naphthyridone.

CP-99,219 is a trifluoronaphthyridone with significant antibacterial activity that includes the family Enterobacteriaceae (MICs for 90% of the strains tested [MIC90s], < or = 0.015 to 0.5 micrograms/ml), Moraxella catarrhalis, Haemophilus influenzae, and gonococci (MICs, < or = 0.015 micrograms/ml). Legionella spp. were also CP-99,219 susceptible, with MICs of 0.008 to 0.12 micrograms/ml. CP-99,219 demonstrated activity greater than that of ciprofloxacin, ofloxacin, or enoxacin against Pseudomonas aeruginosa (MIC90, 1 microgram/ml), Xanthomonas maltophilia (MIC90, 2 micrograms/ml), Staphylococcus haemolyticus (MIC90, 0.5 micrograms/ml), Enterococcus faecalis (MIC90, 1 microgram/ml), and pneumococci (MIC90, 0.12 micrograms/ml). Numerous ciprofloxacin-resistant isolates were susceptible to CP-99,219, a new compound showing potential value for further in vivo trials.     

The comparative activity of fleroxacin, three other quinolones and eight unrelated antimicrobial agents.

The in vitro activity of fleroxacin, a new trifluorinated quinolone was evaluated against 432 bacterial isolates. Fleroxacin was 1- to 2-fold less active than ciprofloxacin and at least as active as ofloxacin and lomefloxacin against most members of the family Enterobacteriaceae. The MICs of fleroxacin for 90% of strains tested (MIC90) were < or = 0.25 micrograms/ml against all isolates of Enterobacteriaceae except Citrobacter freundii (MIC90, 4 micrograms/ml) and Serratia marcescens (MIC90, 2 micrograms/ml). Fleroxacin was as active as ciprofloxacin, ofloxacin and lomefloxacin against Pseudomonas spp, (MIC90 for all quinolones tested were > 8 micrograms/ml). Acinetobacter and Haemophilus influenzae were very susceptible to fleroxacin; however fleroxacin was 1-fold less active than lomefloxacin against Acinetobacter and at least 1-fold less active than ciprofloxacin or ofloxacin against H. influenzae. Methicillin-susceptible and -resistant strains of Staphylococcus epidermidis and methicillin-susceptible strains of S. aureus were very susceptible to fleroxacin, with an MIC90 < or = 1 microgram/ml (range 0.5-1 microgram/ml). Methicillin-resistant S. aureus and Staphylococcus spp. other than aureus and epidermidis were not susceptible to fleroxacin (MIC90 > 8 micrograms/ml). In addition, fleroxacin as well as ciprofloxacin, ofloxacin and lomefloxacin were inactive against Enterococcus spp. (MIC90 > 8 micrograms/ml). Streptococcus pneumoniae and S. pyogenes were resistant to both fleroxacin and lomefloxacin but were very susceptible to ciprofloxacin and ofloxacin. These results suggest that fleroxacin represents a valid therapeutic option in the treatment of infections caused by most Enterobacteriaceae and some species of staphylococcus.     

In vitro susceptibility of Ureaplasma urealyticum clinical isolates to new macrolides.

Nine antimicrobial agents, the new macrolides, rokitamycin and midecamycin acetate, and seven other antibiotics, tetracycline, minocycline, doxycycline, josamycin, erythromycin, spiramycin, and norfloxacin, were studied for their antimicrobial activity against 100 strains of Ureaplasma urealyticum, using a microtiter broth dilution technique. The new macrolides, rokitamycin and midecamycin acetate, had the highest activity, with the MIC against 90% of isolates tested (MIC90) being less than or equal to 0.05 microgram/ml. MICs90 of erythromycin, josamycin, doxycycline, minocycline and tetracycline ranged from 0.1 to 0.78 micrograms/ml. Norfloxacin was least active, with a MIC90 of 12.5 micrograms/ml. Five of 100 strains tested were resistant (MIC greater than or equal to 12.5 micrograms/ml) to tetracycline, and two were resistant to minocycline and doxycycline; all of these were susceptible to rokitamycin and midecamycin acetate.     

In vitro susceptibility of Capnocytophaga species to 29 antimicrobial agents.

A hemoglobin-supplemented medium composed of Columbia agar base supplemented with 1% hemoglobin and 1% Polyvitex was used to investigate the in vitro activity of 29 antimicrobial agents against Capnocytophaga species. Clindamycin was the most active agent, with all strains being inhibited by 0.06 microgram/ml or less. Amoxicillin-clavulanic acid and imipenem were the most active among the beta-lactam antibiotics (MIC for 90% of strains tested [MIC90], 0.50 microgram/ml); other very active drugs were BMY 28142, cefpirome, cefotaxime, ceftazidime, and ceftriaxone (MIC90, 0.06 to 0.50 micrograms/ml), although at least one strain showed resistance to each of these antibiotics (MIC, greater than or equal to 16 micrograms/ml). Ciprofloxacin was the most active among the quinolones, with all strains being inhibited by 0.50 microgram/ml. The MICs of the other four drugs ranged from 0.12 to 4 micrograms/ml. Ampicillin, penicillin G, ticarcillin, aztreonam, and temocillin were moderately active (MIC90, 1 to 8 micrograms/ml; MIC range, less than or equal to 0.03 to greater than 128 micrograms/ml). All strains were uniformly resistant to the aminoglycosides, polymyxin B, vancomycin, trimethoprim, and amphotericin B. Three strains produced beta-lactamase. No significant difference was found between the susceptibility of strains isolated from various sources or patients.     

Comparative in vitro activities of several new fluoroquinolones and beta-lactam antimicrobial agents against community isolates of Streptococcus pneumoniae.

The in vitro susceptibilities of 551 community isolates of Streptococcus pneumoniae from the Canadian province of Ontario to several new fluoroquinolones and beta-lactam antimicrobial agents were determined by a broth microdilution technique. Eight (1.5%) of these isolates were moderately susceptible (MICs, greater than or equal to 0.12 and less than or equal to 1.0 microgram/ml) to penicillin; none was resistant. Temafloxacin, ciprofloxacin, and ofloxacin (MICs for 90% of strains tested, between 1 and 2 micrograms/ml) were the most active fluoroquinolones tested, and BMY-28100 (MIC for 90% of strains tested, 0.25 microgram/ml) was the most active of the new beta-lactams tested.     

In vitro activity of DU-6859a, a new fluorocyclopropyl quinolone.

DU-6859a was tested against 844 recent clinical isolates (most from bacteremias) by using reference MIC determination procedures. The activity of DU-6859a against members of the family Enterobacteriaceae was comparable to that of ciprofloxacin (range of MICs for 90% of isolates [MIC90], < or = 0.015 to 1 microgram/ml), and the highest MICs were observed among Serratia marcescens and Providencia rettgeri isolates. The DU-6859a MIC90 for Pseudomonas aeruginosa and Xanthomonas maltophilia was 0.5 microgram/ml. Pneumococci (MIC90, 0.06 microgram/ml), Haemophilus influenzae (MIC90, < or = 0.004 microgram/ml), Moraxella catarrhalis (MIC90, < or = 0.015 microgram/ml), and pathogenic neisseriae (MIC90, 0.015 to 0.03 microgram/ml) were very susceptible to DU-6859a. All staphylococci had DU-6859a MICs of < or = 1 microgram/ml, including oxacillin- and ciprofloxacin-resistant strains. DU-6859a was very active against isolates resistant to ceftazidime (MIC90, < or = 0.12 microgram/ml), ciprofloxacin (MIC90, < or = 8 micrograms/ml), and gentamicin (MIC90, < or = 1 microgram/ml).     

Comparative in vitro activities of sparfloxacin (CI-978; AT-4140) and other antimicrobial agents against staphylococci, enterococci, and respiratory tract pathogens.

The in vitro activity of sparfloxacin (CI-978; AT-4140) was compared with those of other antimicrobial agents against isolates of staphylococci, enterococci, and various respiratory tract pathogens. Sparfloxacin was the most active drug tested against staphylococci (MIC for 90% of the strains tested [MIC90], 0.125 micrograms/ml) and enterococci (MIC90, 1.0 microgram/ml). It was also active against Haemophilus influenzae (MIC90, less than or equal to 0.06 microgram/ml), Moraxella (Branhamella) catarrhalis (MIC90, 0.125 microgram/ml), Streptococcus pneumoniae (MIC90, 0.5 microgram/ml), and Streptococcus pyogenes (MIC90, 1.0 microgram/ml).     

Comparative antimicrobial activity of ceftibuten against multiply-resistant microorganisms from Belgium

To study the activity of ceftibuten, we obtained multiply-resistant isolates from approximately 20 hospitals in Belgium. Against Enterobacteriaceae, all of the tested comparative compounds were more active than cefaclor, and ceftibuten and tigemonam were the most active of the agents tested. Ceftibuten MIC50s were less than or equal to 1 microgram/ml for most enteric bacilli species and 85% of strains were susceptible (less than or equal to 8 micrograms/ml). This level of activity compared favorably to that recorded for cefaclor (less than or equal to 8 micrograms/ml), cefetamet (less than or equal to 4 micrograms/ml), and cefteram (less than or equal to 1 microgram/ml), that is, 37%, 69%, and 59%, respectively. Ceftibuten, cefetamet, cefteram, and tigemonam were highly active against isolates of Haemophilus influenzae and Neisseria gonorrhoeae. None of the comparative agents were as active as cefaclor against staphylococcal isolates. Against streptococci, cefteram was the most active, and tigemonam the least active of the agents. The MIC90s of ceftibuten for strains of Streptococcus pneumoniae and Streptococcus pyogenes were 2 micrograms/ml and 0.5 microgram/ml, respectively. Strains of Streptococcus agalactiae were resistant to both ceftibuten and tigemonam; cefaclor and cefteram inhibited 100% of isolates of this species. Strains of Enterococcus faecalis and Pseudomonas aeruginosa were consistently resistant to all of the compounds. Overall, ceftibuten exhibited potent activity against many multiply-resistant clinical isolates.     

Comparative susceptibilities of Campylobacter pylori to norfloxacin and other agents.

Twenty-one strains of Campylobacter pylori (Campylobacter pyloridis) were tested for susceptibility to norfloxacin and other agents by the serial agar dilution method. Ampicillin (MIC for 90% of isolates [MIC90], 0.016 micrograms/ml) and famotidine (MIC90, greater than 1,024 micrograms/ml) were, respectively, the most and the least active of the agents tested. Norfloxacin (MIC90, 1 microgram/ml) and imipenem (MIC90, 0.125 micrograms/ml) were substantially active against this organism.     

In vitro activity of Ro 23-6240, a new difluoroquinolone derivative, compared with that of other antimicrobial agents.

Ro 23-6240 is a new difluorinated quinolone antimicrobial agent. Its in vitro activity against a wide range of bacteria was compared with those of other quinolones and beta-lactams. Generally, members of the family Enterobacteriaceae were inhibited by low concentrations of Ro 23-6240 (MIC90 [MIC for 90% of isolates tested], less than or equal to 1 microgram/ml). Ninety percent of Staphylococcus aureus (including methicillin-resistant strains) and Neisseria gonorrhoeae isolates were inhibited by 0.5 microgram/ml. Pseudomonas aeruginosa (MIC90, 2 micrograms/ml) and Bacteroides fragilis (MIC90, 4 micrograms/ml) showed intermediate susceptibility, and Streptococcus pneumoniae (MIC90, 8 micrograms/ml) was less susceptible. Strains resistant to nalidixic acid were less susceptible to all the quinolones tested. The protein binding of Ro 23-6240 (5 micrograms/ml) was 27%.     

Susceptibility of Haemophilus ducreyi to ampicillin and sulbactam in vitro.

The MICs of ampicillin, ampicillin plus sulbactam in equal proportions, and a range of ampicillin concentrations with a constant 0.5 micrograms/ml concentration of sulbactam were determined for 66 strains of Haemophilus ducreyi by an agar dilution technique with standardized inocula prepared by ultrasonication. Fifty-five strains were susceptible to ampicillin alone (MIC range, 0.06 to 1 microgram/ml). The MICs for the 11 resistant strains were (micrograms per milliliter): range, 8 to greater than 16; MIC for 50% of the strains tested (MIC50), greater than 16; MIC90, greater than 16; 8 of them produced beta-lactamase. In the presence of an equal concentration of sulbactam, the MICs for ampicillin-resistant strains were lowered to (micrograms per milliliter): range, 0.125 to 2; MIC50, 0.25; MIC90, 1. In the presence of a fixed 0.5-micrograms/ml concentration of sulbactam, the MICs for the resistant strains were (micrograms per milliliter): range, 0.125 to 2; MIC50, 0.125; MIC90, 0.25. Sulbactam-ampicillin appears to be suitable for the treatment of H. ducreyi infections, especially those caused by ampicillin-resistant strains.     

Evaluation of the in vitro activity of BMY-28142, a new broad-spectrum cephalosporin.

The in vitro activity of BMY-28142, a new cephalosporin, was tested by a broth microdilution system and compared with those of cefotaxime, ceftazidime, cefoperazone, moxalactam, and HR 810 against 747 bacterial isolates, one-third of which were resistant to one or more third-generation cephalosporins. BMY-28142 was the most active drug tested against 326 Enterobacteriaceae with an MIC for 90% of the organisms tested (MIC90) of 1.0 micrograms/ml. Against these Enterobacteriaceae the relative activities were: BMY-28142 greater than HR 810 greater than moxalactam and ceftazidime greater than cefotaxime greater than cefoperazone. For cefotaxime- and cefoperazone-resistant strains, the MIC90 of BMY-28142 was 4.0 micrograms/ml (compared with 0.13 micrograms/ml for susceptible strains). BMY-28142, with an MIC90 of 8.0 micrograms/ml for Pseudomonas aeruginosa, was about half as active as ceftazidime. The relative activities against P. aeruginosa were: ceftazidime greater than BMY-28142 greater than HR 810 greater than cefoperazone greater than moxalactam and cefotaxime. The MIC90 of BMY-28142 against staphylococci was 2.0 micrograms/ml, which was fourfold less active than HR 810, slightly less active than cefotaxime and cefoperazone, and fourfold more active than ceftazidime and moxalactam. BMY-28142 was very active against beta-lactamase-positive and -negative Haemophilus influenzae (MIC90, 0.06 micrograms/ml), Neisseria gonorrhoeae (MIC90, 0.015 micrograms/ml),aand nonenterococcal streptococci. Its activity against Streptococcus faecalis was poor (MIC90, 64 micrograms/ml). BMY-28142 was stable against the several beta-lactamases tested but exhibited little beta-lactamase inhibitory effect.     

Antimicrobial activity of E-1040, a novel thiadiazolyl cephalosporin compared with other parenteral cephems

E-1040, a new parenteral fourth-generation cephalosporin, was tested against greater than 600 bacteremic pathogens and compared with cefotaxime, ceftazidime, and cefpirome. E-1040 activity against Staphylococcus aureus was comparable (MIC90, 8 micrograms/ml) to ceftazidime, but inferior to cefotaxime (MIC90, 2 micrograms/ml) and cefpirome (MIC90, 0.5 microgram/ml). beta-Hemolytic streptococci and most Gram-positive anaerobes were also susceptible to E-1040. Some strains of coagulase-negative staphylococci, all oxacillin-resistant Staphylococcus spp., enterococci, and Bacteroides fragilis group strains were resistant to E-1040 (MIC90, greater than 64 micrograms/ml). Comparative tests for E-1040 and the three other cephalosporins against pseudomonads and nonenteric Gram-negative bacilli showed E-1040 to be generally most active. The E-1040 MIC90 for Pseudomonas aeruginosa was 1 microgram/ml and for ceftazidime it was 4 micrograms/ml. Haemophilus influenzae, Moraxella catarrhalis, and Neisseria spp. has E-1040 MIC90s ranging from 0.12 to 2 micrograms/ml. Neisseria gonorrhoeae, strains resistant to penicillin, did not have markedly elevated E-1040 MICs compared with penicillin-susceptible strains. Enterobacteriaceae species had all MICs of less than or equal to 8 micrograms/ml for E-1040 and cefpirome, indicating activity against strains producing stably derepressed beta-lactamases. E-1040 appeared to be beta-lactamase stable, little influenced by testing systems or media, and was bactericidal. E-1040 seems to have promise as a parenteral beta-lactam for use on strains resistant to "third-generation" cephalosporins and other families of drugs such as aminoglycosides and fluoroquinolones.     

In vitro antibiotic susceptibilities of Neisseria gonorrhoeae isolates in the Philippines.

Antibiotic susceptibility surveillance testing was performed on clinical isolates of Neisseria gonorrhoeae collected in September 1989 in the Philippines. beta-Lactamase was produced by 77 (55%) of 140 isolates. In vitro MIC testing revealed significant resistance to penicillin (MIC for 90% of isolates [MIC90], greater than 64 micrograms/ml), tetracycline (MIC90, 4 micrograms/ml), and cefmetazole (MIC90, 8 micrograms/ml). Spectinomycin resistance was rare (10 of 117), but the MIC90 was 32 micrograms/ml. Isolates were susceptible to fluoroquinolones and cephalosporins at the time of this survey, as evidenced by the MIC90s of ciprofloxacin (0.25 microgram/ml), norfloxacin (2.0 micrograms/ml), ofloxacin (0.625 microgram/ml), cefpodoxime (2.0 micrograms/ml), cefotaxime (1.0 microgram/ml), ceftazidime (0.25 microgram/ml), ceftizoxime (0.25 microgram/ml), and ceftriaxone (0.06 microgram/ml). To date, ceftriaxone resistance has not emerged, despite the widespread use of this antibiotic in the Philippines.     

In vitro activity of DJ-6783 (a keto carboxylic acid) compared with six other orally administered antimicrobial agents

DJ-6783 is a new keto carboxylic acid having an expanded antimicrobial activity when compared with nalidixic acid or cinoxacin. Its usable activity includes the following: Enterobacteriaceae (MIC90, less than or equal to 0.06-4.0 micrograms/ml), Acinetobacter species (MIC90, 0.25-1.0 microgram/ml), Pseudomonas species (MIC90, 1.0-2.0 micrograms/ml), P. aeruginosa (MIC90, 16 micrograms/ml), Staphylococcus species (MIC90, 1.0-32 micrograms/ml), Haemophilus influenzae (MIC900, less than or equal to 0.06 microgram/ml), and Neisseria species (MIC90 less than or equal to 0.06 microgram/ml). The Streptococcus species were resistant to DL-6783 with MIC50 ranging from 16 to greater than 32 micrograms/ml. The drug appears to be bactericidal, minimally influenced by increasing inocula, but resistant mutants can be selected by serial subinhibitory concentration passages of strains in DJ-6783. The resulting resistant organisms also have higher MICs to related drugs such as norfloxacin, cinoxacin, and nalidixic acid. DJ-6783 was the most active organic acid not having structural characteristics of the fluorinated 4-quinolones.     

In vitro activities of two glycylcyclines.

The in vitro activities of two glycylcyclines, CL 329,998 and CL 331,002 (two new semisynthetic tetracyclines), were evaluated in comparison with those of tetracycline and other available oral antimicrobial agents. A total of 523 recent clinical isolates were studied, including strains resistant to tetracycline. Members of the family Enterobacteriaceae were generally > or = 16-fold more susceptible to the glycylcyclines than to tetracycline (although less difference was seen with Proteus spp.). Pseudomonas aeruginosa was modestly susceptible to both new compounds (MIC for 90% of strains tested [MIC90], 16 micrograms/ml). Tetracycline- and methicillin-susceptible and -resistant strains of Staphylococcus aureus were all susceptible to the glycylcyclines (MIC90 < or = 1 microgram/ml). Streptococci (including Streptococcus pneumoniae) and Enterococcus faecalis and Enterococcus faecium displayed a bimodal distribution of susceptibility to tetracycline yet were uniformly susceptible to the glycylcyclines (MIC90 < or = 0.25 microgram/ml). The glycylcyclines were highly potent against Neisseria, Moraxella, Haemophilus, and Bacteroides spp. (MIC90 < or = 0.5 microgram/ml). Strains of Chlamydia spp. (three C. trachomatis strains and one C. pneumoniae strain) were inhibited by < or = 0.25 microgram of CL 329,998 or CL 331,002 per ml. Two strains of Mycoplasma pneumoniae were inhibited by < or = 0.12 microgram of CL 331,002 per ml and by 1 microgram of CL 329,998 per ml. Mycobacterium tuberculosis and Mycobacterium avium were resistant to the two glycylcyclines (MIC > or = 8 micrograms/ml). These results indicate that the two glycylcyclines have potent in vitro activities against a wide range of clinically important pathogenic bacteria.     

Lomefloxacin, a new fluoroquinolone. Studies on in vitro antimicrobial spectrum, potency, and development of resistance

Lomefloxacin (NY-198; SC-47111), a potent new difluoroquinolone, was studied to compare its in vitro activity with that of other antimicrobials against 2194 clinical isolates. Lomefloxacin showed excellent inhibitory and bactericidal activity against strains of Enterobacteriaceae and inhibited greater than 99% of the isolates at a concentration of 4 micrograms/ml or less. Lomefloxacin exhibited good-to-moderate activity against strains of Acinetobacter (MIC90 4 micrograms/ml) and Pseudomonas aeruginosa (MIC90 8 micrograms/ml), but poor activity for Pseudomonas cepacia (MIC90 greater than 16 micrograms/ml). Staphylococcus aureus, and Staphylococcus epidermidis isolates, both oxacillin-susceptible and -resistant strains, were susceptible (MIC90 1 micrograms/ml) to lomefloxacin and the other fluoroquinolones. Strains of Haemophilus influenzae, (MIC90 less than or equal to 0.13 micrograms/ml) Neisseria gonorrhoeae (MIC90 less than or equal to 0.03 micrograms/ml), and Branhamella catarrhalis (MIC90 less than or equal to 0.03 micrograms/ml) were highly susceptible to lomefloxacin. Streptococcal isolates, especially viridans streptococci, were considerably less susceptible to the fluoroquinolones. Overall, lomefloxacin had comparable activity to norfloxacin, fleroxacin, and ofloxacin, and against many facultative anaerobes lomefloxacin was more active than imipenem, cefotaxime, ceftazidime, ticarcillin/clavulanic acid, aztreonam, trimethoprim/sulfamethoxazole and gentamicin. Development of resistance to lomefloxacin by spontaneous mutation was low and comparable to that of other fluoroquinolones. Growth in subinhibitory concentrations resulted in increased resistance to fluoroquinolones for selected test strains.