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Activation of arachidonic acid metabolism in mouse macrophages by bacterial amphiphiles.

The relative activities of lipoteichoic acid (LTA) from four Gram-positive bacteria were compared to different lipopolysaccharide (LPS) preparations for activation of arachidonic acid metabolism in mouse peritoneal macrophages. Total eicosanoid was determined in cultures labeled with [3H]-arachidonic acid. Prostaglandin E2 (PGE2) and leukotriene C4 (LTC4) were determined by EIA analysis. The relative potencies of the different preparations were: smooth LPS from Salmonella abortus > or = Re-LPS from Salmonella minnesota (R-595) > or = LTA from Streptococcus pyogenes approximately Streptococcus faecalis approximately Staphylococcus aureus > or = monophosphoryl lipid A derived from the Re-LPS >> LTA from Bacillus subtilis. Activation of eicosanoid release was inhibited by staurosporin for all of the amphiphiles tested. Treatment of the macrophage cultures with LTA from S. pyogenes, S. faecalis, and S. aureus, either in the presence or absence of indomethacin, desensitized the cells to eicosanoid release on subsequent challenge with LPS. The desensitized cells remained responsive to the phorbol ester phorbol myristate acetate. LPS from Gram-negative bacteria has immunostimulatory and endotoxic activities which result, in part, from the release of eicosanoids and other mediators from activated macrophages. The similarities in the patterns of cell activation by LPS and LTA suggest that lipoteichoic acids might contribute to the pathogenicities of Gram-positive bacteria.

Animals↗

Induction of murine B cell proliferation and immunoglobulin synthesis by some bacterial ribosomes.

Ribosomal preparations from Klebsiella pneumoniae, Haemophilus influenzae, Streptococcus pyogenes, and Streptococcus pneumoniae were investigated with respect to their activating capacity towards murine lymphoid cells. The proliferation of BALB/c spleen cells was induced in a dose-dependent fashion (from 1 to 100 micrograms/ml) by ribosomes of K. pneumoniae, H. influenzae, and S. pyogenes with a peak activity at 48 or 72 hr of culture. The majority of the blast cells induced by these ribosomal preparations were positive for surface-immunoglobulin (S-Ig) and negative for Thy 1.2. Furthermore, K. pneumoniae, H. influenzae, and S. pyogenes ribosomes induced the synthesis of IgM and some IgA. Cell proliferation and induction of IgM production were also demonstrated with the 3 ribosomal preparations using spleen cells from athymic nude (nu+/nu+) mice, Lyb-5-defective CBA/N spleen cells, B cell-enriched and T cell-depleted BALB/c spleen cell suspensions, as well as spleen cells from the Ips gene-deficient C3H/HeJ strain. Cell culture supernatants contained specific anti-ribosome IgM antibodies. Antibodies of other specificities (anti-sheep erythrocytes) were also demonstrated in supernatants from K. pneumoniae-stimulated cultures. Evidence against a possible role of contamination of K. pneumoniae and H. influenzae ribosomes by lipopolysaccharide- or lipid A-associated proteins in this effect is discussed. Ribosomes from S. pneumoniae did not induce 3H-thymidine incorporation nor Ig production. None of the 4 ribosomal preparations was found to stimulate T cell blastogenesis or to induce interleukin-2 production by naive BALB/c spleen cells. Finally, ribosomes from H. influenzae, S. pyogenes, S. pneumoniae but not those of K. pneumoniae stimulated interleukin-1 production by adherent spleen cells, from BALB/c mice.

Animals↗

Genetic elements carrying macrolide efflux genes in streptococci.

Type M resistance to macrolides in Streptococcus pyogenes and Streptococcus pneumoniae is associated to the presence of macrolide efflux genes (mef). These genes are carried by 3 very conserved chromosomal genetic elements: (i) "mega", 5.5 kb, typical of S. pneumoniae, carries mef(E), can insert at different sites in the bacterial chromosome and in other genetic elements, does not have genes encoding putative recombinases or transposases, and it is not conjugative; (ii) Tn1207.3, 54, 52 kb, typical of S. pyogenes, carries mef(A), it integrates at a single specific site in the bacterial chromosome, carries 3 ORFs encoding for putative recombinases, it is transferred by conjugation among different streptococcal species, and its genome resembles that of a bacteriophage; (iii) Tn1207.1, 7.2 kb, is a defective form of Tn1207.3 found in a clonal population of S. pneumoniae, it carries mef(A), it integrates at a single specific site in the bacterial chromosome (the same of Tn1207.3), and it is not conjugative.

Anti-Bacterial Agents↗

BL-S786 (ceforanide), a new parenteral cephalosporin: in vitro studies.

BL-S786 (ceforanide) is a new cephalosporin which showed broad-spectrum activity in vitro against 453 clinical isolates. At a concentration of 3.12 mug/ml, it inhibited greater than 75% of isolates of Escherichia coli, Klebsiella spp., Proteus mirabilis, Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae. Essentially no activity was observed against isolates of Serratia marcescens, and only minimal activity was observed against Enterobacter spp. Its activity was directly related to the size of the inoculum. The minimal bactericidal concentrations were similar to the minimal inhibitory concentrations for isolates of all organisms except S. aureus and S. pyogenes. The minimal bactericidal concentrations were considerably higher than the minimal inhibitory concentrations for these organisms.

Bacteria↗

Plasma bactericidal activity of a new C-5 methyl fluoroquinolone after oral doses of 400 and 800 mg.

The plasma bactericidal activity of a new C-5 methyl fluoroquinolone, OPC-17116, was determined after once-daily oral ingestion of 400 mg and 800 mg in normal, healthy volunteers. OPC-17116 at a 400-mg dose produced plasma bactericidal titers greater than or equal to 1:16 at 12 hours against Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, Haemophilus influenzae, and Moraxella catarrhalis. OPC-17116 bactericidal titers against Pseudomonas aeruginosa were 1:2 or 1:4 at 6 and 12 hours. The plasma bactericidal titers against Streptococcus pyogenes and Streptococcus pneumoniae were 1:4 or greater, but bactericidal titers against Staphylococcus aureus were 1:2 at 12 hours and less than 1:2 at 24 hours. The 800-mg dose of OPC-17116 produced bactericidal titers of at least 1:32 at 12 hours for the Enterobacteriaceae, Haemophilus, and Moraxella, and 1:4 for S. pyogenes and S. pneumoniae, but bactericidal titers against S. aureus were 1:2. These data would suggest that an 800-mg dose of OPC-17116 taken orally once daily would provide adequate concentrations to treat infections due to the pathogens examined in this study.

Administration, Oral↗

Fluid- or surface-phase human salivary scavenger protein gp340 exposes different bacterial recognition properties.

Salivary scavenger receptor cysteine-rich protein gp340 aggregates streptococci and other bacteria as part of the host innate defense system at mucosal surfaces. In this article, we have investigated the properties of fluid-phase gp340 and hydroxylapatite surface-adsorbed gp340 in aggregation and adherence, respectively, of viridans group streptococci (e.g., Streptococcus gordonii and Streptococcus mutans), non-viridans group streptococci (e.g., Streptococcus pyogenes and Streptococcus suis), and oral Actinomyces. Fluid-phase gp340 and surface-phase gp340 bioforms were differentially recognized by streptococci, which formed three phenotypic groupings according to their modes of interaction with gp340. Group I streptococci were aggregated by and adhered to gp340, and group II streptococci preferentially adhered to surface-bound gp340, while group III streptococci were preferentially aggregated by gp340. Each species of Streptococcus tested was found to contain strains representative of at least two of these gp340 interaction groupings. The gp340 interaction modes I to III and sugar specificities of gp340 binding strains coincided for several species. Many gp340 interactions were sialidase sensitive, and each of the interaction modes (I to III) for S. gordonii was correlated with a variant of sialic acid specificity. Adherence of S. gordonii DL1 (Challis) to surface-bound gp340 was dependent upon expression of the sialic acid binding adhesin Hsa. However, aggregation of cells by fluid-phase gp340 was independent of Hsa and involved SspA and SspB (antigen I/II family) polypeptides. Conversely, both gp340-mediated aggregation and adherence of S. mutans NG8 involved antigen I/II polypeptide. Deletion of the mga virulence regulator gene in S. pyogenes resulted in increased cell aggregation by gp340. These results suggest that salivary gp340 recognizes different bacterial receptors according to whether gp340 is present in the fluid phase or surface bound. This phase-associated differential recognition by gp340 of streptococcal species of different levels of virulence and diverse origins may mediate alternative host responses to commensal or pathogenic bacterial phenotypes.

Actinomyces↗

[Toxic shock like syndrome due to S. pyogenes (TSLS)].

Resurgence of severe infection, caused by Streptococcus pyogenes was observed in the USA from the middle of the 1980s. Toxic Shock like Syndrome due to Streptococcus pyogenes (TSLS) has been one of the most life-threatening diseases with soft tissue infections, such as necrotizing fasciitis, myositis, bacteremia and shock. Patients with TSLS has been reported in Europe, USA, Canada, etc. The first report of TSLS in Japan was described by Y. Shimizu and his colleague, Asahi General Hospital, Chiba, 1992. Since then more cases of TSLS, diagnosed by CDC's Criteria, have been found in various parts of Japan, including Chiba prefecture. They are characterised by rapid development of shock and death. Some of the isolated strains from blood or tissues have been identified as S. pyogenes, M3, M1 with SPEA (Streptococcal pyrogenic exotoxin A).

Humans↗

Antimicrobial activity of quinupristin/dalfopristin, a new injectable streptogramin with a wide Gram-positive spectrum.

Quinupristin/dalfopristin (Synercid) is a new injectable streptogramin antibiotic proposed for the treatment of severe antimicrobial infections, that has been shown to be active against Gram-positive, multi-resistant cocci. We compared the in vitro activity of quinupristin/dalfopristin with that of amoxycillin, ampicillin, penicillin, cefixime, ceftriaxone, clindamycin, erythromycin, imipenem, meropenem, oxacillin, piperacillin/tazobactam, teicoplanin and vancomycin. The susceptibility of 37 Staphylococcus aureus (14 MS, 23 MR), 26 Staphylococcus epidermidis (16 MS, 10 MR), 20 Streptococcus pneumoniae, 33 Group A Streptococcus pyogenes, 15 Streptococcus agalactiae, 10 Enterococcus faecalis (1 vancomycin-resistant), 15 Enterococcus faecium (9 van A) was evaluated. Quinupristin/dalfopristin was active against all Gram-positive species tested, including met-R S. aureus (MIC < or = 2 mg/l), met-R S. epidermidis (MIC < or = 2 mg/l), S. pneumoniae (MIC < or = 1 mg/l), ery-R and ery-S streptococci (MIC < or = 1 mg/l). The strains of E. faecalis were generally less susceptible. Time-kill studies confirmed that quinupristin/dalfopristin at 4 x MIC concentration showed a complete bactericidal effect (3 log reduction) in about 4 6 h against all strains tested. A post-antibiotic effect (PAE) of 3.9-5.2 h was observed at 4 x MIC concentration of quinupristin/dalfopristin against staphylococci. A prolonged PAE was obtained for S. pneumoniae (8 h), S. pyogenes (9 h) and S. agalactiae (7 h), while the shortest PAE was seen for E. faecalis and E. faecium (about 4 h).

Anti-Bacterial Agents↗

[Pharmacokinetic, bacteriological and clinical studies on cefpodoxime proxetil in the field of pediatrics].

Pharmacokinetic, bacteriological and clinical studies on cefpodoxime proxetil (CPDX-PR, CS-807), a newly developed oral cephem, were carried out in the treatment of infectious diseases in the field of pediatrics. 1. Since CPDX demonstrates very powerful antimicrobial actions against such Gram-negative bacilli as Escherichia coli, Salmonella sp., Klebsiella pneumoniae and Serratia sp., such Gram-positive cocci as Streptococcus pyogenes and Streptococcus pneumoniae, and beta-lactamase producing Branhamella catarrhalis and Haemophilus influenzae, this drug was thought to be useful for the treatment of pediatric infectious diseases when main causative bacteria in the field of pediatrics were taken into account. 2. When changes in blood and urine concentrations of CPDX following the administration of this drug at 3.7 mg/kg before meal were determined, Cmax and T1/2 were found to be 2.98 micrograms/ml at 2-hour and 1.73 hours, respectively; an urinary excretion rate in the first 6 hours and a maximum urine concentration were 32.5% and 52 micrograms/ml, respectively. 3. Clinically, 8 of 8 patients with the upper respiratory tract infections (100%), 28 of 29 patients with bronchitis and/or pneumonia (96.6%), 3 of 4 patients with otitis media (75%), 2 of 2 patients with sinusitis (100%), 3 of 3 patients with the skin soft tissue infections (100%), 1 of 1 patient with bacterial enteritis (100%) and 11 of 14 patients with urinary tract infections (78.6%) responded well to the treatment with CPDX-PR, showing a 91.8% efficacy rate in all the patients treated. 4. Bacteriologically, Staphylococcus aureus, Staphylococcus epidermidis, S. pyogenes, S. pneumoniae, E. faecalis, B. catarrhalis, H. influenzae, E. coli and Salmonella typhimurium were all eradicated from 5, 1, 4, 6, 1, 5, 5, 11 and 1 patient, respectively. An eradication rate in all the patients examined was 97.5% (39/40). 5. Gastrointestinal symptoms appeared as side effects in 2 of 71 patients (vomiting in 1 and diarrhea in 1), hence, an incidence of side effects was 2.8% (2/71). As for abnormal laboratory findings, eosinophilia, thrombocytosis and increases in GOT and GPT were observed in 3 of 39 patients examined (7.7%), 1 of 39 patients (2.6%) and 2 of 34 patients (5.9%), respectively. In addition, we also examined the effect of the drug on the hemostatic system, but found no changes upon the treatment. Based on these results, it appeared that CPDX-PR was a useful and safe drug in treatment of infectious diseases in the field of pediatrics when administered 2-3 times a day at a dose of 3-6 mg/kg.

Absorption↗

[Different phenotypes of erythromycin-resistant blood isolates in viridans group streptococci]

Macrolide resistance has been widely studied in Streptococcus pyogenes and Streptococcus pneumoniae although not in viridans group streptococci (VGS). We studied 30 blood culture isolates of viridans group streptococci (25 resistant to erythromycin: 10 S. mitis, 8 S. milleri, 6 S. sanguis and 1 S. salivarius; and 5 susceptible: 2 S. mitis, 2 S. milleri and 1 S. sanguis). We carried out a double-disk test and determined MICs. The susceptibility testing was carried out by agar dilution for 14-, 15- and 16-member lactone ring macrolides, as well as for clindamycin and quinupristin-dalfopristin. Fifty-six percent of the erithromycin-resistant strains (6 S. mitis, 6 S. milleri and 2 S. sanguis) showed an MLS(B) phenotype, with a high level of intrinsic resistance to all the macrolides studied and clindomycin; 28% were of the M phenotype (4 S. sanguis, 2 S. mitis and 1 S. salivarius). We found a third resistance phenotype, which was present in 4 strains with MICs of 2-8 µg/ml, with resistance to macrolides and different degrees of resistance to clindamycin. All isolates were fully susceptible to quinupristin-dalfopristin. The MLS(B) and M phenotypes initially described in S. pyogenes and S. pneumoniae are also observed in VGS.

Journal Article↗

Conformation and stability of streptokinases from nephritogenic and nonnephritogenic strains of streptococci.

Conformation and stability of three Sks from Streptococcus equisimilis strain H46A, Streptococcus pyogenes strain A374, and Streptococcus pyogenes strain AT27 were compared by limited proteolysis, CD, and fluorescence measurements and by DSC. The general similarity of the peptide CD spectra in the spectral region 185 to 260 nm indicates the same type of folding for the three proteins. Fluorescence and aromatic CD spectra are consistent with a predominant surface localization of the aromatic amino acids and a low rigidity of their surroundings. A major difference among the three Sks is shown by deconvolution of their excessive heat capacity functions. Deconvolution reveals two energetic folding units in Sk H46A but three energetic folding units in Sk A374 and Sk AT27. Digestion of the Sks with trypsin indicates a reduced sensitivity of the C-terminal region of Sk A374 and Sk AT27 in comparison to Sk H46A. This suggests that amino acids of the C-terminal region participate in the formation of the third folding unit of Sk A374 and Sk AT27.

Amino Acid Sequence↗

In vitro activity of cefcanel versus other oral cephalosporins.

Cefcanel is a new orally absorbed cephalosporin. Its activity was compared with that of cefuroxime, cefaclor, cephalexin, and cefixime against gram-positive and negative aerobic and anaerobic bacteria. Cefcanel had excellent activity against methicillin-susceptible Staphylococcus aureus and Staphylococcus epidermidis, MIC90 1 micrograms/ml, superior to the other oral cephalosporins. However, methicillin-resistant staphylococci were resistant, MIC greater than or equal to 16 micrograms/ml. Streptococcus pyogenes and Streptococcus pneumoniae were inhibited by 0.015-1 micrograms/ml, concentrations comparable to other cephalosporins. Clostridium spp. were inhibited by 0.25 micrograms/ml, 8- to 128-fold lower concentrations than were found for other agents, but the MICs were greater than 64 micrograms/ml for Bacteroides spp. The MIC90 for Moraxella catarrhalis was 1 micrograms/ml, similar to cefuroxime but 16-fold greater than the MICs of cefixime. Escherichia coli and Klebsiella pneumonia which were high beta-lactamase producers were resistant, MICs greater than 64 micrograms/ml, and 50% of Enterobacter cloacae and Citrobacter freundii were resistant. Cefcanel was hydrolyzed by TEM-1, TEM-3 and Moraxella Bro-1 beta-lactamases. Escherichia coli containing TEM-1, 2, 3, 5, 7, and 9 had cefcanel MICs of greater than or equal to 16 micrograms/ml. Although cefcanel inhibited gram-positive species as well as or at lower concentrations than other cephalosporins, it lacked activity against gram-negative species that produced common plasmid beta-lactamase although it inhibited Haemophilus influenzae carrying TEM-1.

Administration, Oral↗

In vitro activity and beta-lactamase stability of the oral cephalosporin BMY-28100.

BMY-28100 was compared with cephalexin, cefaclor, cefixime, and cefteram and found to be more active than the reference cephalosporins against Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus faecalis, and Clostridium difficile. BMY-28100 was the next most active, after cefteram, against Streptococcus pyogenes and Streptococcus pneumoniae. Against gram-negative bacteria, BMY-28100 showed similar activity to that of cefaclor. The antimicrobial activity of BMY-28100, including bactericidal activity, against Staphylococcus aureus was less affected by penicillinase-production than was that of cefaclor. BMY-28100 was more stable than cefaclor against various types of penicillinases, especially against the penicillinase from Staphylococcus aureus.

Cefaclor↗

Intravenous sulbactam/ampicillin in the treatment of pediatric infections.

A total of 82 patients involving 83 episodes of proven or presumed bacterial infection were treated with sulbactam/ampicillin. These included 36 cases of soft tissue infection or abscess, four cases of joint or bone infection, 20 cases of respiratory tract infection (17 cases of pneumonia, two of otitis media, and one of tonsillitis), 15 urinary tract infections, three cases of enterocolitis, one case of infective endocarditis, two cases of septicemia, and two of peritonitis. The causative pathogen was isolated in 48 cases (49 infections). These pathogens included Staphylococcus aureus 13 cases, Staphylococcus epidermidis one, Streptococcus pyogenes two, Streptococcus pneumoniae two, Viridans group streptococcus two, peptostreptococcus one, Haemophilus influenzae one, Escherichia coli 12, Enterobacter cloacae three, Proteus mirabilis one, Acinetobacter calcoaceticus one, Salmonella spp. two, Shigella sonnei one, Bacteroides fragilis one, and polymicrobial infections of various combinations in five cases. No bacterial pathogens were isolated in 34 infections, 14 cases of pneumonia and 15 soft tissue infections. Sulbactam/ampicillin was given by intravenous bolus in a dosage range of 75-450 mg/kg/day in four divided doses for variable periods of time depending on the type and severity of the infection. Of a total of 83 episodes of infections, 80 (96.4%) cases were either cured or improved. Bacteriologic eradication also occurred in 46 (93.9%) of 49 infections. Side effects were diarrhea in two patients, acute hemolytic anemia in one patient, and transient elevations in SGOT and leukopenia in one patient. Side effects disappeared upon completion of treatment. Sulbactam/ampicillin is a safe and effective antibiotic for the treatment of common pediatric infections.

Adolescent↗

Evaluation of the BD Phoenix Automated Microbiology System SMIC/ID panel for identification and antimicrobial susceptibility testing of Streptococcus spp.

The BD Phoenix Automated Microbiology System SMIC/ID panel was evaluated for identification and antimicrobial susceptibility testing (AST) of various streptococci. A group of 97 consecutive clinical isolates of Streptococcus pneumoniae, 23 Streptococcus pyogenes, 24 Streptococcus agalactiae, and 34 viridans streptococci were collected and comparisons made with routine manual methods used in the clinical microbiology laboratory. Overall, in 162 (91%) of 178 isolates, Phoenix identification results demonstrated agreement. For AST results for the 162 isolates that demonstrated identification concordance, the overall essential agreement rate was 98.5%; the category agreement was 94.9%; and the very major error, major error, and minor error rates were 0%, 0.15%, and 5.8%, respectively. Although relatively high minor error rates were observed with S. pneumoniae and beta-lactams, 79.2% of the 77 minor errors were the result of a single log(2) dilution difference. The Phoenix SMIC/ID panel performed favorably and demonstrated the advantages of automation and simple methodology.

Anti-Bacterial Agents↗

Aerobic and anaerobic microbiology of infection after trauma.

Clinical and laboratory data from 1973 to 1988 were retrospectively reviewed to study the microbiology of infection following trauma. A total of 368 specimens obtained from 340 trauma patients showed bacterial growth. The traumas included lacerations (163), blunt trauma (76), penetrating trauma (65), bites (20), and open fractures (10). Anaerobic bacteria only were isolated in 119 (32%) specimens, aerobic bacteria only in 58 (16%), and mixed aerobic-anaerobic flora in 191 (52%). A total of 444 anaerobic (1.2 isolates per specimen) and 267 aerobic or facultative (0.7 per specimen) were recovered. The predominant anaerobic bacteria included Bacteroides fragilis group (119 isolates), Peptostreptococcus spp (113), Clostridium spp (78), Prevotella spp (58), and Fusobacterium spp (23). The predominant aerobic bacteria included Escherichia coli (83), Staphylococcus aureus (61), Streptococcus pyogenes (27), Streptococcus group D (16), and Klebsiella pneumoniae (16). The types of infections included abscesses (109), bacteremia (32), bites (13), empyema (10), osteomyelitis (21), peritonitis (52), thrombophlebitis (12), and wounds (116, including posttraumatic wounds, cellulitis, stump wound, decubitus ulcers, myositis, and fasciitis). S. aureus was isolated at all sites. However, organisms of the oropharyngeal flora predominated in infections that originated from that location (ie, head and neck wounds, and abscesses or bites), and those of the gastrointestinal flora predominated in infections that originated from that site (ie, peritonitis, abdominal abscesses, decubitus ulcers). This study showed the polymicrobial nature of many infections that follow trauma.

Adolescent↗

Minimal inhibitory concentrations and time-kill determination of moxifloxacin against aerobic and anaerobic isolates.

Moxifloxacin is a new oral 8-methoxy-quinolone with a wide spectrum of activity against Gram-negative and anaerobic bacteria, atypical micro-organisms and multi-resistant Gram-positive bacteria. This study was designed to assess the in vitro activity of moxifloxacin against Gram-positive bacteria with different resistance patterns, anaerobes and atypical micro-organisms such as Chlamydia and Mycoplasma. Moxifloxacin had good activity against Streptococcus pneumoniae with all strains inhibited by < or =0.12 mg/l. The minimal inhibitory concentrations (MICs) of moxifloxacin for Streptococcus pyogenes and Streptococcus agalactiae ranged from 0.03 to 0.5 mg/l while those of ciprofloxacin were about two- to four-fold higher (MICs=0.12-1 mg/l). Moxifloxacin was poorly active against enterococci but its activity against Clostridium and Bacteroides spp. was in the same range as that of metronidazole and superior to that of clindamycin. Moxifloxacin was substantially more active than both ciprofloxacin and sparfloxacin against Chlamydia.

Aerobiosis↗

Comparative in vitro activity of gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin and trovafloxacin against 4151 Gram-negative and Gram-positive organisms.

Gatifloxacin, grepafloxacin, moxifloxacin and trovafloxacin are fluoroquinolones with enhanced Gram-positive activity while retaining broad-spectrum activity against Gram-negative pathogens. Levofloxacin and ciprofloxacin are older quinolones with broad activity against Gram-negative pathogens and borderline activity against some Gram-positive organisms. We compared the in vitro activity of these compounds against 4151 Gram-negative and -positive organisms. Gatifloxacin, grepafloxacin, moxifloxacin and trovafloxacin were highly active against penicillin sensitive and resistant Streptococcus pneumoniae, Staphylococcus aureus, Streptococcus pyogenes and Streptococcus agalactiae. Ciprofloxacin and levofloxacin were active but less potent. All compounds were highly active (overall) against Gram-negative pathogens with ciprofloxacin being the most active agent against Pseudomonas aeruginosa. Our data indicate that the advanced fluoroquinolones will be important compounds for treating infections caused by Gram-positive and Gram-negative pathogens.

Anti-Infective Agents↗

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