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PubMed1992

The microbial etiology and antimicrobial therapy of adults with acute community-acquired sinusitis: a fifteen-year experience at the University of Virginia and review of other selected studies.

Pretreatment sinus puncture was performed on 339 patients with acute community-acquired sinusitis (ACAS) between 1975 and 1990. Bacterial species recovered in titers of greater than or equal to 10(4) colony-forming units per milliliter (CFU/ml) from 383 sinus aspirates included Streptococcus pneumoniae, 92 (41%); Haemophilus influenzae, 79 (35%); anaerobes, 17 (7%); streptococcal species, 16 (7%); Moraxella catarrhalis, 8 (4%); Staphylococcus aureus, 7 (33%); and other, 8 (4%). Viruses (rhinovirus, parainfluenza virus, and influenza virus) and fungi (Aspergillus, zygomycoses, Phaeohyphomycis, Pseudallescheria, and Hyalohyphomycis) have also been reported to cause ACAS. Posttreatment sinus puncture was performed on 220 of the 339 patients in six studies to evaluate efficacy of selected antimicrobial agents in producing bacteriologic cure. Ampicillin, 500 mg four times daily; amoxicillin, 500 mg three times daily; trimethoprim-sulfamethoxazole, twice a day; cefaclor, 500 mg four times daily; bacampicillin, 800 mg twice a day; cyclacillin, 500 mg three times a day; cefuroxime axetil, 250 mg twice daily; amoxicillin-clavulanate, 500/125 three times daily; and loracarbef 400 mg twice daily, given in 10-day courses, produced bacteriologic cure in more than 90% of patients. Early studies were done before beta-lactamase-producing strains of H. influenzae were a frequent cause of ACAS in Charlottesville. Management of therapeutic failures is a difficult problem for which diagnostic and therapeutic sinus puncture and lavage, prolonged antimicrobial therapy, steroid therapy, and evaluation of allergy, immunodeficiency, and surgically correctable lesions of the osteomeatal complex are recommended.

Acute Disease↗
PubMed1992

Antimicrobial therapy of pediatric patients with sinusitis.

The mainstay of medical therapy for acute and subacute sinusitis is the selection of an antimicrobial agent based on an appreciation of the usual bacterial pathogens that include Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Amoxicillin is appropriate therapy for patients with uncomplicated sinusitis in geographic areas in which the prevalence of beta-lactamase-producing pathogens is less than 20%. If a patient does not respond to amoxicillin or in areas in which there is a high prevalence of beta-lactamase-producing bacterial species, alternative antimicrobials include amoxicillin-clavulanate, erythromycin-sulfisoxazole, trimethoprim-sulfamethoxazole, cefaclor, cefuroxime axetil, and cefixime. Cefixime, which is less active against S. pneumoniae than most of these antimicrobials, should be reserved for patients who do not improve with amoxicillin. Amoxicillin-potassium clavulanate, cefuroxime axetil, and erythromycin-sulfisoxazole have the most comprehensive antibacterial spectra.

Acute Disease↗
PubMed1991

Antimicrobial resistance of pneumococci in children with acute lower respiratory tract infection in Pakistan.

87 strains of Streptococcus pneumoniae isolated during three winter seasons (1986-89) from the blood of children with acute lower respiratory tract infection (ALRI) in Pakistan were serotyped and tested for susceptibility to a range of antimicrobial agents. 97% of isolates were resistant to at least one antimicrobial drug. 62% had decreased susceptibility to co-trimoxazole (trimethoprim/sulphamethoxazole) (31% were fully resistant) and 39% were resistant to chloramphenicol. All isolates were susceptible to erythromycin, cefaclor, cephalothin, ceftriaxone, cefuroxime, rifampicin, vancomycin, and clindamycin. 29% of isolates were neither vaccine types nor vaccine-related types. Serotype distribution and antimicrobial susceptibility varied significantly during the three winter seasons. No single serotype was found in all three winters. The findings highlight the need for surveillance of antimicrobial resistance and serotype distribution of S pneumoniae in developing countries as a guide both to the choice of agent for treatment of pneumococcal infections, especially ALRI, and to the formulation of new pneumococcal conjugate vaccines for use in young children.

Child, Preschool↗
PubMed1987

Retention properties of internal-surface reversed-phase silica packing and recovery of drugs from human plasma.

The properties of internal-surface reversed-phase silica packings developed for use in high-performance liquid chromatography, were investigated with regard to the effects of mobile phase conditions (pH, ionic strength, nature and concentration of organic modifiers, ion-pairing agent and surfactant) on the retention of some selected compounds having different polarities. The results indicated that pi-electron interactions play the main role in solute retention, although it is weaker than that on phenylsilica supports, and that weak cation-exchange properties exert a secondary effect on the retention of ionic solutes. The ion-pairing effect was found to be markedly weakened in mobile phases containing an anionic counter ion. In contrast, the addition of a surfactant (SDS) caused a marked increase in the retention of certain drugs at low pH and expanded the pH range of the mobile phase applicable to plasma samples. Based on these findings, the separation and recovery of several drugs (probenecid, lidocaine, cefpiramide and cefaclor) from human plasma were investigated, with emphasis on their protein bindings. The contour chromatogram of human plasma is also demonstrated in relation to the selection of the detection wavelength.

Blood Proteins↗
PubMed1994

High-performance liquid chromatographic method for the determination of cefpodoxime levels in plasma and sinus mucosa.

A selective HPLC method is described for the determination of cefpodoxime levels in plasma and sinus mucosa. Sample preparation included solid-phase extraction with a C8 cartridge. Cefpodoxime and cefaclor (internal standard) were eluted with methanol and analyzed on an optimised system consisting of a C18 stationary phase and a ternary mobile phase (0.05 M acetate buffer pH 3.8-methanol-acetonitrile, 87:103, v/v) monitored at 235 nm. Linearity and both between- and within-day reproducibility were assessed for plasma and sinus mucosa samples. Inter-assay coefficients of variation were lower than 13.6% (n = 10) for plasma (0.2 micrograms/ml) and lower than 12.4% (n = 5) for sinus mucosa (0.25 micrograms/g). The quantification limit was 0.05 micrograms/ml for plasma and 0.13 micrograms/g for tissue. The method was used to study the diffusion of cefpodoxime in sinus mucosa.

Ceftizoxime↗
PubMed1985

Evaluation of in vitro antibacterial activity of enoxacin: comparison with other orally absorbed antimicrobial agents, proposed disk diffusion test interpretive criteria, and quality control limits.

The antibacterial activity of enoxacin was assessed by a standard microdilution susceptibility test method against 6,096 consecutive clinical isolates at four clinical laboratories and compared with that of norfloxacin and cefaclor. Its activity was comparable to that of norfloxacin; both inhibited over 90% of Enterobacteriaceae at 0.5 micrograms/ml. Resistance to enoxacin [minimum inhibitory concentration (MIC) greater than 4 micrograms/ml] was observed in only 18 of 4,076 Enterobacteriaceae (0.5%, 36 of 650 nonfermentative gram-negative bacilli (5.5%), and 6 of 836 staphylococci (0.7%). Relatively poor activity was observed against streptococci. An additional 618 selected clinical isolates were tested with enoxacin and were compared with nine other orally absorbed antimicrobial agents. The greatest activity was observed with enoxacin, norfloxacin, and cotrimoxazole, but some difference were noted with individual species. Results of enoxacin disk diffusion susceptibility testing of 487 isolates were correlated with the MICs, analyzed, and interpretive criteria were determined. With MIC breakpoints of: susceptible = less than or equal to 2.0 micrograms/ml, intermediate = 4.0 micrograms/ml, and resistant = greater than 4.0 micrograms/ml, the corresponding preliminary disk diffusion zone diameter breakpoints for the 10-micrograms enoxacin disk are: susceptible greater than or equal to 18 mm, intermediate 15-17 mm, and resistant less than or equal to 14 mm. Quality control zone diameter limits were determined for three standard QC organisms.

Anti-Bacterial Agents↗
PubMed1987

RO23-6240, a new orally absorbed quinolone: in vitro comparison with other broad-spectrum oral antimicrobial agents and imipenem.

A total of 626 clinical isolates were tested for their susceptibility to RO23-6240 and other broad-spectrum antimicrobial agents. RO23-6240 showed good activity against strains of Enterobacteriaceae, Acinetobacter, and P. aeruginosa. RO23-6240 MIC90s ranged from 0.032 to 4 micrograms/ml for these strains. RO23-6240 also showed good activity against staphylococci, both methicillin-susceptible and -resistant strains. The activity in vitro of RO23-6240 was comparable with that of norfloxacin and ofloxacin, and more active than imipenem, trimethoprim-sulfamethoxazole, cefaclor, and amoxycillin/clavulanate potassium. As with the other quinolones tested, increases in inoculum size produced moderate increases in the MICs and MBCs of RO23-6240.

Anti-Bacterial Agents↗
PubMed1988

Characterization of beta-lactam antagonist in Supplement C.

In the course of using Mueller-Hinton agar with 1% Supplement C (SC) (Difco, Detroit, MI) as a susceptibility test medium for Haemophilus influenzae, one lot of SC was encountered whose use was associated with markedly increased ampicillin MICs. Acidimetric and chromogenic cephalosporin filter paper disc tests of SC failed to detect beta-lactamase activity. Macrobroth dilution MIC tests to determine substrate specificity showed SC to antagonize benzylpenicillin and ampicillin but not cephalothin, cefazolin, or cefaclor, with the antagonism being prevented by the addition of clavulanic acid. High pressure liquid chromatographic analysis of reference and reaction solutions of benzylpenicillin with SC showed almost complete degradation of benzylpenicillin to benzylpenicilloic acid after 24 hr at 37 degrees C. For two other lots of SC that had passed MIC quality control testing, similar high pressure liquid chromatographic studies demonstrated slow conversion of small amounts of benzylpenicillin to benzylpenicilloic acid. These findings indicate that the beta-lactam antagonism by SC was due to the presence of a contaminating beta-lactamase directed primarily toward the penicillins.

Anti-Bacterial Agents↗
PubMedDate not supplied

In vitro activity evaluations of cefdinir (FK482, CI-983, and PD134393). A novel orally administered cephalosporin.

Cefdinir, a so-called third-generation oral cephalosporin was tested in vitro against over 700 pathogens from patients with bacteremia. Cefdinir was very active against the Enterobacteriaceae with a 50% minimum inhibitory concentration (MIC50) value range of less than or equal to 0.03-8 micrograms/ml. The enteric species having the highest MIC90S (greater than or equal to 16 micrograms/ml) were Citrobacter freundii, and the enterobacters, Morganella morganii, Proteus vulgaris, and Serratia marcescens. Cefdinir was generally two- to fourfold less active than cefixime, but markedly more potent with a wider spectrum compared with older oral cephalosporins, cefaclor or cefuroxime. In contrast to cefixime, cefdinir inhibited Staphylococcus aureus (MIC90, 1 micrograms/ml) and other staphylococci. Pneumococci, beta-hemolytic streptococci, Haemophilus influenzae, Moraxella catarrhalis, and pathogenic Neisseria spp. (MIC90S, 0.12-0.5 micrograms/ml) were cefdinir susceptible, but Pseudomonas aeruginosa, oxacillin-resistant staphylococci and Bacteroides fragilis gr. strains were resistant. Cefdinir was generally bactericidal with a minimal inoculum effect at 10(6) colony-forming units per spot. Cefdinir beta-lactamase hydrolysis by some recently described extended broad spectrum beta-lactamases was suspected. Cefdinir exhibited a wide, balanced spectrum for an oral cephalosporin indicating possible clinical use against susceptible pathogens in respiratory tract, urinary tract, genital and cutaneous infections.

Cefdinir↗
PubMedDate not supplied

Ceftibuten: a new orally absorbed cephalosporin. In vitro activity against strains from the United Kingdom.

The in vitro activity of ceftibuten was studied in 572 bacterial strains and was compared with the activity of other orally administered beta-lactams. Ceftibuten displayed high activity against the Enterobacteriaceae, generally being 16-fold more active than cefuroxime, cefaclor, cephalexin, or amoxicillin-clavulanic acid. Its activity was comparable to cefixime. There was little ceftibuten or cefixime activity against staphylococci (MIC90s greater than or equal to 64 micrograms/ml) and reduced activity against Streptococcus pneumoniae (MIC90, 16 micrograms/ml). Haemophilus influenzae and Neisseria spp. were highly susceptible to ceftibuten and cefixime. The protein binding of ceftibuten was 77%, and the primary target site was PBP 3. A high degree of stability to beta-lactamase hydrolysis was observed.

Administration, Oral↗
PubMedDate not supplied

Ceftibuten and bactericidal kinetics. Comparative in vitro activity against Enterobacteriaceae producing extended spectrum beta-lactamases.

Ceftibuten, compared to cefixime, cefetamet, cefpodoxime, loracarbef, cefprozil, cefuroxime, cefaclor, and cefadroxil, was the most active oral cephalosporin derivative against Enterobacteriaceae producing plasmid-encoded broad spectrum beta-lactamases. In a pharmacodynamic model, ceftibuten was bactericidal for Haemophilus influenzae and Streptococcus pneumoniae at concentrations simulating human serum levels following 200 mg, p.o., b.i.d.

Administration, Oral↗
PubMedDate not supplied

In vitro activity of cefpodoxime compared with other oral cephalosporins tested against 5556 recent clinical isolates from five medical centers.

A multicenter study was conducted in which the in vitro activity of cefpodoxime (the active metabolite of the prodrug ester cefpodoxime proxetil) was compared with those of cefixime, cefuroxime, cefaclor, cefadroxil, and clarithromycin against 5556 recent clinical isolates. Cefpodoxime demonstrated potent activity against members of the Enterobacteriaceae, in particular against species generally resistant to the established oral cephalosporins such as Proteus vulgaris [minimum inhibitory concentration (MIC)50, 0.12 microgram/ml], Providencia rettgeri (MIC50, 0.015 microgram/ml), and Serratia marcescens (MIC50, 2 micrograms/ml). Cefpodoxime was very effective against the fastidious organisms most frequently associated with respiratory infections, such as Streptococcus pneumoniae (MIC90, 0.12 microgram/ml), Haemophilus influenzae (MIC90, 0.12 microgram/ml), and Moraxella catarrhalis (MIC90, 1 microgram/ml). In contrast to other orally administrated third-generation cephalosporins (cefixime or ceftibuten), cefpodoxime demonstrated reasonable activity against oxacillin-susceptible staphylococci, with MIC50 ranging from 1 to 2 micrograms/ml. All cephalosporins tested demonstrated poor activity against Pseudomonas spp., Xanthomonas spp., Enterococcus spp., and oxacillin-resistant staphylococci. Cefpodoxime had the widest spectrum of activity of all tested oral cephalosporins.

Administration, Oral↗
PubMedDate not supplied

The North American component (the United States and Canada) of an International Comparative MIC trial monitoring ofloxacin resistance.

Common lots of reference MIC (minimum inhibitory concentration) method reagents were used to monitor ofloxacin, a newer fluoroquinolone, and 13 other drugs against 3200 recent clinical isolates in February-April 1992. Five medical centers in the United States and Canada contributed 640 strains per facility as follows: Escherichia coli, Staphylococcus aureus, coagulase-negative staphylococci, Klebsiella spp., and Pseudomonas aeruginosa (100 strains each); Streptococcus pneumoniae (40 strains); and Enterobacter cloacae, Serratia marcescens, Salmonella spp., Haemophilus influenzae, and Moraxella catarrhalis (20 strains each). Quality-control strains were processed concurrently, MICs recorded, and data processed at a common location. Selected ofloxacin-resistant isolates were retested at a reference laboratory to confirm resistances and determine cross-resistant patterns. Results indicate the following (a) fluoroquinolones were superior in usable spectrum of activity to other orally administered drugs (for example, cefaclor, cefixime, ampicillin, amoxicillin-clavulanate, minocycline, oxacillin, and trimethoprim-sulfamethoxazole); (b) ofloxacin and ciprofloxacin were generally equal to gentamicin and cefotaxime against commonly isolated Gram-negative pathogens; (c) fluoroquinolone resistance was rare among enteric bacilli, pneumococci (ciprofloxacin > ofloxacin), H. influenzae, and M. catarrhalis, but more common among oxacillin-resistant staphylococci and P. aeruginosa; (d) cross resistance was generally observed between ofloxacin and ciprofloxacin but was species or genus dependent; and (e) a new fluoroquinolone, levofloxacin, demonstrated promising activity against contemporary pathogens.

Anti-Bacterial Agents↗
PubMed1994

Multicenter in vitro comparative study of fluoroquinolones after four years of widespread clinical use.

In vitro activities of ciprofloxacin, fleroxacin, lomefloxacin, ofloxacin, and seven other oral antimicrobials including amoxicillin-clavulanic acid (A/C), oxacillin, cefaclor, cefixime, cefuroxime, erythromycin, and trimethoprim-sulfamethoxazole (T/S) were evaluated against 1708 fresh bacterial isolates from four hospital laboratories approximately 4 years after the introduction of ciprofloxacin. T/S and ofloxacin had the lowest MIC90s and greatest percentage of susceptible strains overall, followed by the other three quinolones. Quinolones were the most active drugs tested against Gram-negative bacteria, with little variation in the activity among the four compounds against most species. Quinolone resistance was detected to some degree in the majority of Gram-negative species tested, with Pseudomonas, Acinetobacter, Xanthomonas, and Providencia demonstrating the highest percentage of resistant strains. Ofloxacin and ciprofloxacin were relatively more active against Gram-positive bacteria than were fleroxacin and lomefloxacin, but T/S and A/C had more susceptible strains than any of the quinolones. Oxacillin-resistant staphylococci, enterococci, and streptococci exhibited the least quinolone susceptibility. This study showed that while resistance is developing among several previously susceptible bacterial species, quinolones remain important alternatives for the oral treatment of many types of infections. Actions to prevent or limit resistance will be important to maintain the viability of the quinolones as therapeutic agents in both hospital and community environments.

Anti-Bacterial Agents↗
PubMed1994

In vivo therapeutic efficacy of cefdinir (FK482), a new oral cephalosporin, against Staphylococcus aureus and Haemophilus influenzae in mouse infection models.

Cefdinir (FK482), a new oral cephalosporin, displayed potent oral activity versus induced infections in mice. In studies using beta-lactamase-nonproducing (beta LAC-) and -producing (beta LAC+) Staphylococcus aureus strains, respective PD50s (in mg/kg) were 11 and 24 for preventing subcutaneous abscess and 2.7 and 2.3 for preventing lethal systemic infection. In studies using beta LAC- and beta LAC+ Haemophilus influenzae, respective PD50s were 5.8 and 3.1 for preventing lethal systemic infection. Time-kill studies versus H. influenzae showed that 6- to 12-mg/kg dosing was effective in reducing viable counts of these strains in blood by > or = 100-fold by 24 h after challenge. This in vivo performance was comparable to or exceeded values generated by cefaclor, cefpodoxime proxetil, and ampicillin.

Administration, Oral↗
PubMed1995

Comparative in vitro activity of furopenem against aerobic bacteria isolated from pediatric patients.

The in vitro activity of the oral penem furopenem (WY-49605, 545555, SUN5555, and ALP201) was tested against clinical bacteria isolated from pediatric patients. Furopenem was compared with clarithromycin, cefpodoxime, amoxicillin, amoxicillin-clavulanate, cefaclor, cefixime, and cefuroxime. Furopenem demonstrated consistent activity against Escherichia coli [minimum inhibitory concentration (MIC90) = 1.0 microgram/ml)] Klebsiella pneumoniae (MIC90 = 2.0 micrograms/ml), Salmonella enteriditis and Shigella spp. (MIC90 = 1.0 microgram/ml), and beta-lactamase-positive or -negative Haemophilus influenzae (MIC90 = 1.0 microgram/ml) and Moraella catarrhalis (MIC90 = 1.0 microgram/ml). Furopenem was also active against a number of the Gram-positive organisms tested including methicillin-susceptible Staphylococcus aureus and penicillin-susceptible Streptococcus pneumoniae. These results suggest a potential application for this agent in the treatment of children as outpatients.

Bacteria, Aerobic↗
PubMed1996

Comparison of five different susceptibility test methods for detecting antimicrobial agent resistance among Haemophilus influenzae isolates.

The detection of antimicrobial agent resistance among ninety-eight Haemophilus influenzae isolates was assessed by six different antibiotic test methods: agar dilution on Mueller-Hinton agar supplemented with 5% lysed horse blood (MH-LHB), E-test using both Haemophilus test medium (HTM) agar and chocolate Mueller-Hinton (CMH) agar plates, Vitek Haemophilus susceptibility cards, and three overnight microdilution systems that included two commercial systems, Micro-Media and MicroScan, and the reference broth microdilution method using HTM broth. Agents tested in the study included ampicillin, amoxicillin/clavulanic acid (A/C), cefaclor, cefuroxime, cefotaxime, ceftriaxone, chloramphenicol, and trimethoprim/sulfamethoxazole. Both the reference HTM microbroth dilution method and agar dilution correctly classified all nine of the beta-lactamase negative ampicillin resistant (BLNAR) isolates. Each of the other test methods failed to detect one of the BLNAR strains, either because of growth failure (Micro-Media and MicroScan) or miscategorization of an isolate as susceptible (E-Test HTM, E-Test CMH, and Vitek). None of the test methods detected all six isolates identified as A/C resistant by HTM microbroth dilution. Of the remaining antimicrobials tested, ampicillin and cefuroxime yielded data that could be compared by all test methods. The very major, major, and minor errors for these two antimicrobials in comparison to the reference HTM microdilution method were as follows: Micro-Media (1.7%, 0%, and 4.8%); MicroScan (11.9%, 0%, and 8.1%); E-Test HTM (1.6%, 0%, and 2.0%); E-Test CMH (1.6%, 1.6%, and 4.6%); Vitek (8.1%, 0%, and 3.1%); and agar dilution on MH-LHB (0%, 0%, and 4.6%). Micro-Media and MicroScan panels failed to support the growth of 4.1% and 5.1% of the isolates, respectively.

Chloramphenicol↗
PubMedDate not supplied

[beta-Lactamases of Branhamella catarrhalis and their phenotypic implications].

Of the 50 strains of beta-lactamase-producing Branhamella catarrhalis isolated at Saint Joseph's Hospital (Paris) that were studied, 94% produced BRO-1 type beta-lactamase and 6% produced the BRO-2 type. We examined the transfer of BRO-1 and BRO-2 genes and found that, among 7 donor strains producing BRO-1, all were able to transfer the gene for BRO-1 production by conjugation. Of the 4 donor strains producing BRO-2, 2 were able to transfer the gene for BRO-2 production by conjugation. Three BRO-1 beta-lactamase-producing transformants were obtained from total DNA extracted from 3 strains producing BRO-1. Plasmid bands were demonstrated in strains of B. catarrhalis, but no change in plasmid profiles was seen in beta-lactamase-positive recombinants, supporting previous studies that suggested the beta-lactamases are chromosomal. In vitro activity of oral beta-lactams was tested for 67 strains of B. catarrhalis (56 beta-lactamase-producing strains). Cefixime, cefpodoxime and the combination ampicillin-clavulanic acid were very active against the beta-lactamase-producing strains. BRO-1 beta-lactamase appears to affect the activity of cefaclor, cefuroxime and loracarbef. BRO-2 beta-lactamases have no effect on the activity of these cephalosporins. Cefixime and cefpodoxime seemed the least affected by beta-lactamase production.

Anti-Bacterial Agents↗