Comparative In Vitro Activity of Newer Cephalosporins Against Anaerobic Bacteria

The in vitro susceptibilities of 408 recent clinical isolates of anaerobic bacteria against cefaclor, cephalexin, cephalothin, cefazolin, cefamandole, and cefoxitin were compared by an agar dilution technique. Against gram-positive bacteria, especially peptococci, peptostreptococci, and propionibacteria, cephalexin and cefaclor were significantly less active than cephalothin (P < 0.05). Cephalexin was also less active than cephalothin against clostridia and lactobacillus (P < 0.05). Against gram-negative bacteria, major differences were observed primarily with Bacteroides fragilis, against which cephalexin, cefazolin and cefoxitin were all significantly more active than cephalothin (P < 0.001). At concentrations of 16 μg per ml, however, all cephalosporins showed high in vitro activity, except against Lactobacillus species and B. fragilis. Cephalothin, cefazolin and cefamandole were considerably more active against the former, whereas cefoxitin was distinctly more active against the latter.     

In Vitro Activity of Sodium Fusidate Against Anaerobic Bacteria

The microtiter broth dilution method was employed to determine the in vitro susceptibility of 525 recent clinical isolates of anaerobic bacteria to sodium fusidate. The minimal inhibitory concentrations of sodium fusidate ranged from 相似文献   

Comparative In Vitro Activity of Five Cephalosporin Antibiotics Against Salmonellae

The in vitro activities of five cephalosporin antibiotics against 121 strains of salmonellae were compared. Cefamandole and cefaclor were more potent than cefazolin, and these three drugs were more active than cephalothin and cephalexin.     

Comparative In Vitro and Bactericidal Activity of Oxazolidinone Antibiotics Against Multidrug-Resistant Enterococci

Increasing resistance among enterococci poses a considerable therapeutic problem. In this study, we evaluated the comparative in vitro activity of two investigational oxazolidinone antibiotics, eperezolid and linezolid, versus clinical isolates of multidrug-resistant enterococci. One hundred isolates (16 Enterococcus faecalis, 69 E. faecium, 10 E. gallinarum, 2 E. casseliflavus, 1 E. avium, 1 E. hirae, and 1 E. raffinosus) evaluated were collected from diverse geographic areas in North America and Europe from 1991 to 1995. Eperezolid MIC₅₀ and MIC₉₀ were 1.0 μg/mL and 2.0 μg/mL (1.0–2.0 μg/mL range). Linezolid MIC₅₀ and MIC₉₀ were 2.0 μg/mL and 2.0 μg/mL (0.5–2.0 μg/mL range), respectively. MICs were the same at 10³ CFU/mL and 10⁸ CFU/mL initial inoculum. In time-kill experiments using 10 strains and concentrations of 4 μg/mL, 8 μg/mL, and 16 μg/mL (achievable serum concentrations) of eperezolid and linezolid, there was a 2 log₁₀ reduction of growth for 2 of 10 isolates tested using eperezolid and a 1 log₁₀ reduction for 50% of isolates with both agents. There was indifferent bactericidal killing when either oxazolidinone was combined with gentamicin, ampicillin, or streptomycin for isolates lacking these resistances. This study demonstrates these oxazolidinone agents to have excellent in vitro activity versus multidrug-resistant enterococci.     

In Vitro Activity of Mezlocillin and Its Related Compounds Against Aerobic and Anaerobic Bacteria

A total of 900 clinical isolates of aerobic (462 isolates) and anaerobic (438 isolates) bacteria were tested against mezlocillin in comparison with other penicillins, and the aerobes were also tested against cephalothin, cefoxitin, and cefamandole. Among penicillins, mezlocillin was the most effective against Escherichia coli, Klebsiella pneumoniae, Salmonella species, Pseudomonas aeruginosa, and Bacteroides fragilis. Mezlocillin was more effective than cephalothin against Klebsiella pneumoniae.     

Comparative Activities of Selected Beta-Lactam Antibiotics Against Haemophilus influenzae

The comparative activities of ampicillin, cefamandole, cefoxitin, cefaclor, and cefatrizine against both beta-lactamase-producing and non-beta-lactamase-producing isolates of Haemophilus influenzae were determined by using an agar dilution susceptibility test procedure. Ampicillin was the most active drug tested against non-beta-lactamase-producing isolates, whereas cefamandole was most active against beta-lactamase-producing strains.     

In Vitro Activity of Ticarcillin Against Anaerobic Bacteria Compared with That of Carbenicillin and Penicillin

A total of 334 clinical anaerobic isolates were tested in an anaerobic glove box by the agar dilution technique for susceptibility to clinically achievable levels of ticarcillin, carbenicillin, and penicillin. Thirty-two micrograms or less of penicillin per milliliter inhibited 91% of all strains, whereas 100 μg of carbenicillin and ticarcillin per ml inhibited 95 and 98%, respectively. A total of 82% (85 strains) of Bacteroides were inhibited by penicillin, and 93 and 96% were inhibited by carbenicillin and ticarcillin, respectively. Thirteen (24%) of 55 strains of Bacteroides fragilis tested were resistant to 32 μg of penicillin per ml, and 6 (11%) and 3 (5%) were resistant to 100 μg of carbenicillin and ticarcillin per ml, respectively. Within the therapeutic range, ticarcillin was the most effective of the three penicillins tested against B. fragilis subsp. fragilis.     

Antibacterial Activity of Selected Beta-Lactam and Aminoglycoside Antibiotics Against Cephalothin-Resistant Enterobacteriaceae

The in vitro antibacterial activity of four β-lactam antibiotics (cefatrizine [BL-S640], cefamandole, cefoxitin, and carbenicillin) and three aminoglycosides (amikacin, gentamicin, and tobramycin) was determined against 197 strains of cephalothin-resistant Enterobacteriaceae. Eighty strains were found to be gentamicin-sensitive, and 117 were found to be gentamicin-resistant. Carbenicillin was the most active β-lactam antibiotic against gentamicin-sensitive Serratia marcescens and Enterobacter spp. Cefoxitin was the most active β-lactam antibiotic against the remaining gentamicin-sensitive and -resistant Enterobacteriaceae, including Providencia stuartii and indole-positive Proteus spp. Cefatrizine exhibited little activity against the organisms studied. Cefamandole was less active than cefoxitin and carbenicillin. Amikacin was the most effective agent in vitro. With the exception of S. marcescens, cefoxitin appeared to be the next most promising agent in vitro against gentamicin- and cephalothin-resistant Enterobacteriaceae.     

Comparison of the In Vitro Activity of Several Cephalosporin Antibiotics Against Gram-Negative and Gram-Positive Bacteria Resistant to Cephaloridine

The in vitro activity of each of two oral [cefatrizine (BL-S640), cephalexin] and three parenteral (cefamandole, cefazolin, cephapirin) cephalosporin antibiotics was compared with that of cephalothin against 168 clinical isolates of gram-negative and gram-positive bacteria selected as resistant to 20 μg of cephaloridine per ml on the basis of agar dilution susceptibility test data. Each of the five other cephalosporins inhibited a greater percentage of gram-negative bacillary isolates than did cephalothin or cephaloridine, with minimal inhibitory concentration values ranging 2- to 50-fold lower. Significant differences between minimal inhibitory concentrations of the compounds tested were also observed in tests against strains of Streptococcus faecalis and of methicillin-resistant Staphylococcus aureus. Potential advantages of including more than a single cephalosporin antibiotic in the panel of antibiotics used for routine susceptibility testing, suggested by these observations, are discussed.     

Comparative In Vitro Activity of Five Cephalosporins Against Lactobacilli

Of five parenteral cephalosporins tested against 43 lactobacilli, cephaloridine, cefazolin, and cefamandole were the most active inhibitory and bactericidal agents. Timed-kill analysis revealed a slow bactericidal effect, with significant declines in mean minimal bactericidal concentration values at 48 h versus 24 h.     

Activity of Four Cephalosporin Antibiotics In Vitro Against Bovine Udder Pathogens and Pathogenic Bacteria Isolated from Newborn Calves

The in vitro activity of chephaloridine, cephalexin, cefatrizine (BL-S640), and cephapirin (BL-P-1322) was evaluated by the serial dilution method against pathogenic gram-positive and gram-negative bacteria isolated from bovine udders and neonatal calf diseases. Cephapirin showed the comparatively greatest activity against the most common streptococcal species associated with bovine mastitis, whereas cephaloridine exhibited the best activity against Staphylococcus aureus. Cefatrizine was more active than the other cephalosporins against the gram-negative bacteria studied. In general, the minimal bactericidal concentration of each cephalosporin was two- to fourfold lower than the comparative value reported in the literature against the same type of pathogen of human origin.     

In Vitro Activity of Ceftaroline against 623 Diverse Strains of Anaerobic Bacteria

The in vitro activities of ceftaroline, a novel, parenteral, broad-spectrum cephalosporin, and four comparator antimicrobials were determined against anaerobic bacteria. Against Gram-positive strains, the activity of ceftaroline was similar to that of amoxicillin-clavulanate and four to eight times greater than that of ceftriaxone. Against Gram-negative organisms, ceftaroline showed good activity against β-lactamase-negative strains but not against the members of the Bacteroides fragilis group. Ceftaroline showed potent activity against a broad spectrum of anaerobes encountered in respiratory, skin, and soft tissue infections.With the continuing emergence of novel patterns of resistance to commonly used antimicrobial agents, alternative therapies are needed to treat serious infections. Ceftaroline is a novel, parenteral, broad-spectrum cephalosporin that exhibits bactericidal activity against Gram-positive organisms, such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate S. aureus, and multidrug-resistant Streptococcus pneumoniae (MDRSP) strains, as well as common Gram-negative pathogens (8, 12, 14, 16, 18-22). Ceftaroline is currently in development for the treatment of complicated skin and skin structure infections and community-acquired pneumonia.Anaerobic bacteria are common pathogens in a variety of pleuropulmonary infections, including aspiration pneumonia, lung abscesses, and empyema (1, 3, 6, 15). However, many laboratories do not culture for anaerobes (9), diminishing awareness of the role of anaerobes in these infections. The main anaerobic pathogens isolated from these infections include Prevotella melaninogenica (∼25%), Prevotella intermedia (∼30%), Fusobacterium species (∼39%), Gram-positive cocci (∼30%), and Veillonella species (∼35%) (7). Cephalosporins such as cefoxitin have been used for the therapy of aspiration pneumonias. Although cefoxitin is active against most respiratory anaerobes, it has poor activity against the newer resistant strains of members of the family Enterobacteriaceae and MRSA. The activity of ceftaroline against Gram-positive anaerobes is similar to that of amoxicillin-clavulanate, and non-β-lactamase-producing Gram-negative strains generally have low ceftaroline MICs (present study), suggesting that ceftaroline might have an adequate spectrum of activity for therapy for some cases of aspiration pneumonia.To investigate the broader potential of ceftaroline, we compared its in vitro activity against 623 unique clinical isolates of anaerobic bacteria representing 5 Gram-negative bacterial genera and 17 Gram-positive bacterial genera to the activities of ceftriaxone, metronidazole, clindamycin, and amoxicillin-clavulanate.The reference agar dilution procedure described in CLSI document M11-A7 was used (5). The organisms were recovered from a variety of clinical specimens and were stored at −70°C in 20% skim milk. Identification was accomplished by standard phenotypic methods or by partial 16S rRNA gene sequencing for strains that could not be identified phenotypically (13, 17). Quality control strains Bacteroides fragilis ATCC 25285, Clostridium difficile ATCC 700057, and Staphylococcus aureus ATCC 29213 were included on each day of testing.The antimicrobial agents were obtained as follows: ceftaroline was from Forest Laboratories, Inc. (New York, NY); ceftriaxone, vancomycin, and metronidazole were from Sigma-Aldrich, Inc. (St. Louis, MO); and amoxicillin and clavulanate were from GlaxoSmithKline (Research Triangle Park, NC). The agar dilution plates were prepared on the day of testing.The strains were taken from the freezer and transferred twice to ensure purity and good growth. Cell paste from 48-h cultures was suspended in brucella broth to achieve the turbidity of a 0.5 McFarland standard, and the mixture was applied to plates with a Steers replicator to deliver approximately 10⁵ CFU/spot. The plates were incubated for 44 h at 37°C in an anaerobic chamber. The MIC was the lowest concentration that completely inhibited growth or that resulted in a marked reduction in growth compared with that for the drug-free growth control (5).A summary showing the MIC range, MIC₅₀, MIC₉₀, and percent susceptibility is presented in Table ​Table1.1. The cumulative ceftaroline MIC distributions for all groups of strains are displayed in Table ​Table22.

TABLE 1.

Summary of ceftaroline and comparator agent MICs, by species or group

Activity of Methacycline, Related Tetracyclines, and Other Antibiotics Against Various L-Forms and Their Parent Bacteria In Vitro

The activity of methacycline against microbial L-forms and their parent bacteria was compared with that of oxytetracycline, chlortetracycline, tetracycline, and demethylchlortetracycline, as well as with that of 22 other antibiotics which included examples of major groups of antibiotics. The L-forms and bacteria used were Streptococcus faecalis, S. faecium, S. faecalis var. zymogenes, Staphylococcus aureus (three strains), Proteus mirabilis (two strains), Pseudomonas aeruginosa, Escherichia coli (two strains), Sarcina flava, Serratia marcescens, and Klebsiella pneumoniae. The five tetracyclines had similar activities and were more active against L-forms than bacterial forms, except that the bacterial form of S. flava was more susceptible than the L-form. In general, other antibiotics (except the penicillins) were more active against L-forms than bacterial forms. There were certain exceptions where the bacterial form was more susceptible than the L-form. These included the effect of polymyxin B and colistin on P. aeruginosa, E. coli, and P. mirabilis, and the effect of gentamicin on P. aeruginosa, E. coli, S. flava, and S. marcescens.     

Relative Morphological Effects Induced by Cefoxitin and Other Beta-Lactam Antibiotics In Vitro

Cefoxitin, a new semisynthetic cephamycin antibiotic, induced filament formation at subinhibitory concentrations with a beta-lactamaseless strain of Enterobacter cloacae (HSC 18410 M66). The extent of filament induction by cefoxitin was similar to that seen with cephalothin, cefazolin, and benzylpenicillin. Filament induction by cefoxitin was markedly less than that seen with cephalexin, carbenicillin, ticarcillin, cephradine, and cephapirin. Antibiotics which failed to induce filaments at any level tested included cephaloridine, cephacetrile, cephalosporin C, the cephamycins, 6-aminopenicillanic acid, 7-aminocephalosporanic acid, A16884, A16886, and FL-1060. Those antimicrobial agents tested which lacked an aromatic substituent in the 7-position (for cephems) or in the 6-position (for penams) did not induce filaments. These observations suggest a possible relationship between filament induction of the test organism and the molecular nature of constituents in the 7- or 6-position of beta-lactams.     

In Vitro Activity of 5-Episisomicin in Bacteria Resistant to Other Aminoglycoside Antibiotics

Eighty-seven isolates of Pseudomonas, Enterobacteriaceae, and Staphylococcus, chosen because of their resistance to other aminoglycosides, were tested for susceptibility to 5-episisomicin. Tests were performed in Mueller-Hinton agar and also, with 38 of these isolates, in Mueller-Hinton broth. Of Enterobacteriaceae, 85 and 95.5% were inhibited by 5 and 10 mug of 5-episisomicin per ml, respectively. Amikacin inhibited 74 and 91% of the strains at 10 and 20 mug/ml, respectively. Fifty-four percent of P. aeruginosa were inhibited by 5-episisomicin and amikacin. Eighty-three percent of S. aureus were inhibited by netilmicin and amikacin, whereas only 50% were inhibited by 5-episisomicin. Isolates resistant to 5-episisomicin were most often resistant to the other aminoglycosides and occurred in gram-negative bacilli that did not carry aminoglycoside-modifying enzymes. Five of 23 isolates that carried a 6'-N-acetyltransferase (AAC-6') and one of two that carried an aminoglycoside 3-acetyltransferase were resistant to and acetylate 5-episisomicin. Strains carrying other aminoglycoside-modifying enzymes were inhibited by 5-episisomicin. Thus, 5-episisomicin is a promising aminoglycoside not attacked by most aminoglycoside-modifying enzymes. Resistance will probably most often be based upon nonenzymatic mechanisms which will also affect other aminoglycosides.     

Activity of Five Aminoglycoside Antibiotics In Vitro Against Gram-Negative Bacilli and Staphylococcus aureus

The in vitro susceptibility to BB-K8, butirosin, gentamicin, sisomicin, and tobramycin of seven groups of clinically significant gram-negative bacilli and Staphylococcus aureus was assessed by using the International Collaborative Study-World Health Organization criteria. The activity of gentamicin, sisomicin, and tobramycin generally paralleled each other. Sisomicin was the most potent compound by weight and usually demonstrated the most rapid rate of killing. BB-K8 and butirosin were less potent, but higher serum levels may be achieved with these agents. BB-K8 generally showed the greatest ratio between achieveable mean peak serum levels and concentrations needed to inhibit [Formula: see text] of each group of organisms tested. Additionally, BB-K8 was active against six of seven highly gentamicin-resistant strains. All of these antibiotics showed diminished activity at pH 6.4 but only gentamicin and sisomicin showed occasionally enhanced activity at pH 8.4.     

In Vitro Susceptibilities of Anaerobic Bacteria to Josamycin

A total of 132 strains of anaerobic bacteria were tested for susceptibility to josamycin, using a broth dilution technique. All strains of Peptococcus species, Peptostreptococcus species, and Bacteroides fragilis were inhibited by 2 μg or less per ml. Seventy percent of these susceptible strains were also killed by 2 μg or less of josamycin per ml. However, 2 of 12 Clostridium species and 6 of 10 Fusobacterium species had minimum inhibitory concentrations of 32 μg or more per ml.     

In Vitro Activity of Penicillins Against Anaerobes

The in vitro susceptibility of 162 anaerobic isolates from clinical material were tested to pencillin G, BL-P1654, and carbenicillin. Penicillin G and BL-P1654 showed good activity against Bacteroides fragilis, but only 60% of strains were susceptible to carbenicillin at achievable blood levels (128 μg/ml).     

Standardized Antimicrobial Disc Susceptibility Testing of Anaerobic Bacteria: In Vitro Susceptibility of Clostridium perfringens to Nine Antibiotics

The in vitro susceptibility of 43 strains of Clostridium perfringens to nine antibiotics was determined by a standardized test for rapid-growing anaerobes. Good correlation was established between the agar dilution susceptibility and the disc diffusion susceptibility results. The inhibition zone diameters around the antibiotic discs, however, were generally much smaller than those of gram-negative anaerobes previously studied. All of the strains tested were susceptible in vitro to chloramphenicol, clindamycin, doxycycline, minocycline, penicillin, and vancomycin. Erythromycin showed poor in vitro activity against this organism, with only 7% of the strains susceptible, 72% intermediate in susceptibility, and 21% resistant. In tests of the 43 strains against lincomycin, 58% were susceptible, 32.5% were intermediate in susceptibility, and 9.5% were resistant. Against tetracycline, 37% of the strains were intermediate in susceptibility and the rest were susceptible.