In vitro activity of rosoxacin against Haemophilus influenzae

The in vitro activity of rosoxacin was compared to that of ampicillin, cefoxitin, chloramphenicol, and rifampin, against 94 clinical isolates of Haemophilus influenzae. The results indicated that rosoxacin had significantly better in vitro activity against H. influenzae than the other antibiotics evaluated in this study. In addition, rosoxacin was an effective antimicrobial agent against isolates of H. influenzae that were resistant to ampicillin due to beta-lactamase production.     

In vitro antimicrobial activity of tigemonam, a new orally administered monobactam.

At five geographically separate medical centers, over 6,000 clinical bacterial isolates were tested for their susceptibility to tigemonam by the broth microdilution method. The antimicrobial spectrum of tigemonam was similar to that of aztreonam, but with two differences. Aztreonam was more active against Pseudomonas spp., and tigemonam was more active against some streptococci. Tigemonam was highly resistant to hydrolysis by the eight beta-lactamase enzymes tested. A significant (greater than a fourfold increase in the MICs of tigemonam) inoculum effect occurred when 3 of 13 isolates were tested with inocula of 5 X 10(5) and 1 X 10(7) CFU/ml. Tigemonam was bactericidal for all but 1 of the 13 isolates. Of the four quality-control strains recommended by the National Committee for Clinical Laboratory Standards, only Escherichia coli ATCC 25922 provided on-scale results. The proposed MIC quality-control range of tigemonam for E. coli ATCC 25922 is 0.13 to 0.5 micrograms/ml.     

In vitro activity of 79 antimicrobial agents against Corynebacterium group D2.

Corynebacterium group D2 (CGD2) is involved in urinary tract infections in patients with underlying predisposing factors. This microorganism is highly resistant to a number of antimicrobial agents. We tested the activities of 79 antimicrobial agents against CGD2. beta-Lactams, aminoglycosides, and macrolides were ineffective. Fluorinated quinolones showed irregular activities, ofloxacin being the most active one. Doxycycline, rifampin, and mainly glycopeptides (vancomycin and teicoplanin) were the most active antibiotics against CGD2.     

In vitro activity of ceftibuten against Haemophilus influenzae and Branhamella catarhallis

The in vitro activity of ceftibuten, a new orally administered cephalosporin, was assessed against clinical isolates of Haemophilus influenzae and Branhamella catarrhalis. The activity of ceftibuten was compared to that of ampicillin, amoxicillin-clavulanic acid, and three oral cephalosporins, cefaclor, cefuroxime, and cefixime. With the exception of rare beta-lactamase-negative ampicillin-resistant strains of H. influenzae, resistance to ceftibuten was not observed with any of the study isolates. Ceftibuten was more active than amoxicillin/clavulanic acid for beta-lactamase-positive and -negative strains of H. influenzae; it was less active than this combination for B. catarrhalis. Ceftibuten was essentially equivalent in activity to cefixime against both Haemophilus and Branhamella but more active than cefaclor and cefuroxime against these two organisms.     

In vitro and in vivo activities of meropenem and comparable antimicrobial agents against Haemophilus influenzae, including beta-lactamase-negative ampicillin-resistant strains.

The in vitro activity of ampicillin, cefotaxime, meropenem, panipenem, imipenem and biapenem was assayed using ampicillin-susceptible, beta-lactamase-positive and beta-lactamase-negative ampicillin-resistant (BLNAR) Haemophilus influenzae isolated recently in Japan. Against ampicillin-susceptible isolates, cefotaxime was the most potent (MIC(90) 0.016 mg/mL). Both cefotaxime and meropenem (MIC(90) of both, 0.5 mg/L) were the most potent against beta-lactamase-positive isolates. Against BLNAR isolates, meropenem (MIC(90) 0.5 mg/L) was the most potent. In murine bronchopneumonia caused by ampicillin-susceptible and BLNAR H. influenzae, cefotaxime showed the best efficacy, followed by meropenem. Our results indicate that meropenem could be a useful intravenous agent for infections caused by H. influenzae, including BLNAR strains.     

Comparative activities of LY 164846 and other orally administered beta-lactam antibiotics against Haemophilus influenzae.

LY 164846, a new oral cephalosporin, demonstrated very good inhibitory and bactericidal activities against Haemophilus influenzae irrespective of the production of beta-lactamase by the test strains. However, its activity was not markedly superior to that of either Augmentin (amoxicillin plus clavulanate) or cefaclor.     

In vitro activity of several antimicrobial agents against genital mycoplasmas.

The increasing resistance of genital mycoplasmas to tetracyclines is a serious problem, since this group of antibiotics is one of the few that is effective against virtually all species of mycoplasmas. Tetracyclines are also used to treat many sexually transmitted diseases. In this study, we assessed the susceptibility of Mycoplasma hominis and Ureaplasma urealyticum to macrolides, tetracyclines, spectinomycin, and trospectomycin by the agar dilution method. For M hominis, trospectomycin was the most active agent. Spectinomycin, tetracycline, and doxycycline had comparable mycoplasmatic activity, and the macrolides were ineffective. Against U urealyticum, spectinomycin and trospectomycin were the most active drugs, and were at least twofold more active than the macrolides and tetracyclines.     

Comparative in vitro activity of imipenem against Haemophilus influenzae and Haemophilus parainfluenzae.

A microdilution broth method was used to test 77 clinical isolates of Haemophilus influenzae and Haemophilus parainfluenzae, including beta-lactamase-positive and -negative strains, for susceptibility to ampicillin, chloramphenicol, and imipenem. Except for ampicillin against beta-lactamase-producing strains (MIC for 90% of strains [MIC90], greater than or equal to 128 micrograms/ml), all three antimicrobial agents had comparable in vitro activity (MIC90, less than or equal to 1 microgram/ml) against these bacterial strains.     

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 activity of cefditoren and other antimicrobial agents against 288 Streptococcus pneumoniae and 220 Haemophilus influenzae clinical strains isolated in Zaragoza, Spain

In vitro cefditoren antimicrobial activity was tested against 288 Streptococcus pneumoniae and 220 Haemophilus influenzae clinical strains isolated in our hospital from January 2005 to May 2006 by agar dilution and broth microdilution method, respectively. MICs were also determined for 13 and 10 comparison drugs, respectively. The pneumococci tested comprised 113 (39.2%) penicillin susceptible, 91 (31.6%) penicillin intermediate, and 84 (29.2%) penicillin resistant. Cefditoren was the most active drug on the basis of the MICs (MIC(90)=0.5 microg/mL), followed by ceftriaxone and levofloxacin (MIC(90)=1 microg/mL). Cefditoren MICs ranged from 0.25 to 1 microg/mL for ceftriaxone-resistant isolates, with a modal MIC of 0.5 microg/mL and an MIC(90) of 1.0 microg/mL. No S. pneumoniae isolates evaluated in this study showed MICs to cefditoren higher than 1 microg/mL (MIC range, 4 microg/mL). Against H. influenzae (Hi beta+), the rank order of intrinsic activity (MIC(90), microg/mL) was cefditoren (0.03) < cefixime (0.06)8.0).     

In vitro activity of cefixime (CL284635) and other antimicrobial agents against Haemophilus isolates from pediatric patients

In vitro activity of cefixime, an experimental oral third-generation cephalosporin and 7 other antimicrobials (ampicillin, augmentin, trimethoprim/sulfamethaxazole, cefamandole, cefotaxime, cefuroxime, and cefaclor) were determined for 150 isolates of Haemophilus obtained from pediatric patients. All (109) non-typeable H. influenzae isolates were sensitive to cefixime and cefotaxime. All (18) isolates of H. parainfluenzae were sensitive to cefotaxime, cefuroxime, cefamandole, cefaclor, and augmentin; 17/18 isolates were sensitive to cefixime. All (23) isolates of H. influenzae-b were sensitive to cefixime, cefotaxime, cefamandole, cefuroxime, cefaclor, and augmentin. Only 10/23 were sensitive to tri/sulfa. 137 of 150 (91.3%) isolates had MBCs equivalent to their MICs for cefixime, compared to 149/150 (99.3%) isolates for cefotaxime. Approximately 95% (143/150) of isolates tested had MICs of less than or equal to 0.06 microgram/ml for cefixime. These data demonstrate that in vitro cefixime has good activity against Haemophilus isolates and it is very similar to the activity of cefotaxime.     

In vitro evaluation of nicotinamide riboside analogs against Haemophilus influenzae.

Exogenous NAD, nicotinamide mononucleotide, or nicotinamide riboside is required for the growth of Haemophilus influenzae. These compounds have been defined as the V-factor growth requirement. We have previously shown that the internalization of nicotinamide riboside is energy dependent and carrier mediated with saturation kinetics. Thionicotinamide riboside, 3-pyridinealdehyde riboside, 3-acetylpyridine riboside, and 3-aminopyridine riboside were prepared from their corresponding NAD analogs. These compounds and several other nicotinamide riboside analogs were evaluated for their ability to support the growth of H. influenzae and for their ability to block the uptake of [carbonyl-14C]nicotinamide riboside by H. influenzae. 3-Aminopyridine riboside blocked the uptake of [carbonyl-14C]nicotinamide riboside and inhibited the growth of H. influenzae when NAD, nicotinamide mononucleotide, or nicotinamide riboside served as the V factor. The antibacterial activity of 3-aminopyridine riboside was found to be specific for H. influenzae but had no effect on the growth of Staphylococcus aureus or Escherichia coli. In additional experiments by reversed-phase high-performance liquid chromatography, it was determined that whole cells of H. influenzae degrade 3-aminopyridine adenine dinucleotide to 3-aminopyridine riboside, which is then internalized. Inside the cell, 3-aminopyridine riboside has the ability to interfere with the growth of H. influenzae by an undetermined mechanism.     

In vitro and in vivo activity of combination antimicrobial agents on Haemophilus ducreyi

OBJECTIVES: Development of single dose antibiotic treatments for chancroid has been followed by drug-resistant Haemophilus ducreyi in endemic areas. We examined the activity and interactions of antimicrobial agents and combinations against H. ducreyi. METHODS: We evaluated the in vitro susceptibility of three virulent strains of H. ducreyi to ceftriaxone, azithromycin, rifabutin and streptomycin, and each two-drug combination by the agar dilution method. We then tested each two-antibiotic combination for activity by the chequerboard method. Lastly, we chose the antibiotic combination with the lowest fractional inhibitory concentration index (FICI) and tested combined sub-therapeutic doses, the highest doses which had no effect alone on lesion healing compared with controls, for in vivo interaction in the temperature-dependent rabbit model of H. ducreyi infection. RESULTS: Each H. ducreyi strain was susceptible in vitro to each antibiotic and two-antibiotic combination, and combined ceftriaxone and streptomycin had the lowest FICI at 0.63. In five treated animals versus three untreated controls, combined sub-therapeutic doses of ceftriaxone (0.05 mg/kg) and streptomycin (10 mg/kg) reduced mean (SD) duration of culture positivity from 7.3 (1.1) to 2.6 (1.7) days (P<0.001), time to 50% reduction in lesion size from 9.7 (1.5) to 5.8 (0.8) days (P<0.005), and time to resolution of ulcer from 11.7 (2.3) to 6.6 (1.7) days (P<0.05). CONCLUSIONS: Ceftriaxone and streptomycin have in vivo synergic interaction against H. ducreyi lesions in the temperature-dependent rabbit model of infection. Antibiotic combinations may be evaluated clinically as single-dose therapy for chancroid.     

In vitro susceptibility of Haemophilus somnus to 33 antimicrobial agents.

Minimal inhibitory concentrations of 33 antimicrobial agents for Haemophilus somnus were determined by the agar dilution method. The tested H. somnus strains were highly susceptible to penicillin G, ampicillin, colistin, and novobiocin. They were not susceptible to spiramicin and sulfadimethoxine, and streptomycin-resistant strains were found.     

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.     

Susceptibility trends of haemophilus influenzae and Moraxella catarrhalis against orally administered antimicrobial agents: five-year report from the SENTRY Antimicrobial Surveillance Program

The assessment of orally administered antimicrobial susceptibilities of common pathogens that cause community-acquired respiratory tract infections (CARTI) has become exceedingly important due to the number of office visits for this indication. Numerous local, regional and global studies have documented the susceptibilities of Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis, the most common CARTI pathogens. SENTRY Antimicrobial Surveillance Program sites in North and Latin America, and Europe were requested to send a combined total of 100 isolates of these pathogens to the local monitor for reference broth microdilution testing (1997-2001). This study compared the susceptibility profiles of H. influenzae and M. catarrhalis isolates (13,370 strains) from the three geographic regions over a five year period. beta-lactamase mediated ampicillin resistance among H. influenzae was highest among North American isolates (27.9%) compared to Latin America and Europe (16.2 to 16.3%), although it was noted that during the five year study period, ampicillin resistance was steadily increasing in the latter two regions. Cefprozil (84.3% susceptible) and clarithromycin (81.1% susceptible) were also less active against North American H. influenzae isolates. Latin American isolates were much less susceptible to trimethoprim/sulfamethoxazole (T/S; 59.3%) compared to the other regions (75.8 to 78.6%). M. catarrhalis isolates were also significantly less susceptible to T/S in Latin America (10.5% resistance). The production of beta-lactamase enzymes among the M. catarrhalis isolates exceeded >95% in all three regions during the five year period. The fluoroquinolones (FQ) remained very active against these two respiratory pathogens with rare isolates with elevated FQ MIC results. It is apparent from this investigation that many commonly prescribed empiric treatments remain viable therapeutic options for CARTI caused by these two Gram-negative respiratory tract pathogens.     

In vitro activity of sparfloxacin and other antimicrobial agents against genital pathogens.

The in vitro activity of sparfloxacin was determined for 60 strains of Neisseria gonorrhoeae, 15 strains of Chlamydia trachomatis and 40 strains each of Gardnerella vaginalis, Mycoplasma hominis, and Ureaplasma urealyticum and compared with those of ampicillin, azithromycin, clarithromycin, erythromycin, ofloxacin, temafloxacin and tetracycline. Sparfloxacin was active against all the strains studied and appeared to be the most potent quinolone tested. Sparfloxacin had the lowest MICs against N. gonorrhoeae (MICs 0.002-0.06 micrograms/ml). Its MICs against C. trachomatis (0.03-0.06 micrograms/ml) were higher than those of clarithromycin but lower than those of the other antimicrobial agents. Sparfloxacin was particularly active against tetracycline-susceptible as well as resistant strains of M. hominis (MICs, 0.06 micrograms/ml) and U. urealyticum (MICs 0.125-1 micrograms/ml). Because of this in vitro activity and its tissue distribution, sparfloxacin might be a valuable therapeutic agent for treating major bacterial sexually transmitted diseases.     

In vitro activities of piperacillin against beta-lactamase-negative ampicillin-resistant Haemophilus influenzae

The in vitro activities of piperacillin (PIP) against beta-lactamase-negative ampicillin (AMP)-resistant (BLNAR) Haemophilus influenzae were compared with those of cefotaxime (CTX) and ceftriaxone (CRO), and the potency of PIP as therapy for meningitis caused by BLNAR is also discussed. PIP showed good activity (MIC at which 90% of strains are inhibited, 0.25 micro g/ml) against 69 BLNAR strains, and its activity was comparable to that of CRO and superior to that of CTX. No significant correlation was observed between the MICs of PIP and CTX or CRO or AMP, whereas a high correlation was observed between the MICs of CTX and CRO. In the killing study, PIP showed potent bactericidal activity compared with those of CTX and CRO. By microscopic examination, PIP caused the formation of a spindle and short filamentous cells with bulges and induced cell lysis in BLNAR strains, while treatment with CTX and CRO resulted in the formation of large, spherical cells without any obvious lysis. The affinity of Bocillin FL, a fluorescent penicillin used for determination of the 50% inhibitory concentration (IC(50)s) for penicillin-binding proteins (PBPs), to PBPs 3a and 3b of BLNAR strains was drastically decreased compared with that to an AMP-susceptible strain (ATCC 33391). In the case of the BLNAR strains, the IC(50)s for PBPs 1a, 1b, and 2 were similar to those for the PBPs of ATCC 33391. Since the affinity of binding to PBPs 3a and 3b of the BLNAR strains decreased drastically, the second targets among the PBPs were PBP 2 for PIP, PBP1 (1a and 1b) for CTX and CRO. In conclusion, PIP showed excellent activities against BLNAR strains in a manner different from those of cephem antibiotics, suggesting that it could be a candidate therapeutic agent for the treatment of meningitis caused by BLNAR strains.