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Statewide survey of the antimicrobial susceptibilities of Haemophilus influenzae producing invasive disease in Tennessee.

Between October 1, 1980, and September 30, 1981, a prospective statewide study of Haemophilus influenzae infections identified 220 culture-proved systemic infections. Of these, 92% were caused by H. influenzae type b. Antimicrobial susceptibility testing of the type b isolates showed that 17% were resistant to ampicillin, but virtually all were susceptible to chloramphenicol, trimethoprim-sulfamethoxazole, cefaclor and rifampin. Ampicillin resistance is common in all parts of Tennessee and chloramphenicol remains the drug of choice for initial therapy of systemic H. influenzae infections.

Ampicillin↗

In vitro activities of oral antimicrobial agents against penicillin-resistant Streptococcus pneumoniae: implications for outpatient treatment.

We tested 83 penicillin-intermediate (Peni) and 50 penicillin-resistant (Penr) isolates of Streptococcus pneumoniae against eight oral antimicrobials. Clarithromycin's MICs (minimal inhibitory concentration) were generally the same or one to two dilutions less than those of azithromycin. Seventy-two percent of Peni isolates were susceptible to clarithromycin and azithromycin, in contrast to 42% and 40%, respectively, of Penr isolates. Cefuroxime activity exceeded that of cefprozil, which exceeded that of cefaclor, in Peni isolates. For all three cephalosporins, MICs of 90% of isolates tested were > or = 3 dilutions higher for Penr isolates than for Peni isolates. Percentages of Peni isolates susceptible to clindamycin and tetracycline were 92% and 83%, respectively, and 78% and 82% for Penr. Only 49% of Peni isolates and 4% of Penr isolates were susceptible to trimethoprim-sulfamethoxazole. Azithromycin, clarithromycin, cefuroxime, cefprozil, clindamycin, and tetracycline may be useful in treating infections caused by Peni S pneumoniae, but Penr isolates are frequently resistant to both old and newer agents.

Administration, Oral↗

Probenecid: an unexplained effect on cephalosporin pharmacology.

1 The influence of probenecid on serum levels and urinary excretion of orally administered cephradine and cefaclor has been investigated. 2 Probenecid caused serum levels of both antibiotics to be increased and also prolonged. Urinary excretion of antibiotic activity was slightly but not significantly decreased by probenecid during the initial 6 h postdosing. It was significantly increased in 6-12 h urine, but only a small percentage of the doses were excreted during that period. 3 The increased serum levels of antibiotic were greater than could be accounted for by reduced elimination rate alone. Possible mechanisms to account for increased circulating levels of antibiotic in the presence of probenecid are discussed in the light of previous observations on probenecid induced changes in tissue distribution of beta-lactam antibiotics.

Adolescent↗

Evaluation of the E test for antimicrobial susceptibility testing of Porphyromonas gingivalis.

The antimicrobial susceptibilities of 81 recent clinical Porphyromonas gingivalis isolates and two reference strains were determined by the E test, a new method, and were compared with the minimal inhibitory concentrations for these strains obtained by the reference agar dilution method on supplemented Brucella blood agar. The following agreements were obtained: benzylpenicillin 100%, ampicillin 96%, cefaclor 82%, cefuroxime 91%, erythromycin 93%, clindamycin 99%, tetracycline 66%, doxycycline 89%, metronidazole 77% and ciprofloxacin 77%. Very major discrepancies were observed with ciprofloxacin. This study indicates that the E test is an acceptable method to determine the susceptibility of P. gingivalis for most antimicrobials.

Ampicillin↗

[Serotypes and antimicrobial susceptibility of Streptococcus pneumoniae from clinical specimens].

Studies were made on 66 strains of Streptococcus pneumoniae which were obtained from clinical specimens in 1991 through 1993 and showed 19 mm or less of disk inhibition zone diameter (DIZD) against 1 microgram oxacillin (MPIPC) disk. The studies included the determination of their serotypes, antimicrobial susceptibility, and comparison between microbroth dilution (MD) method and Kirby-Bauer (K-B) method. In the study of distribution of serotypes, additional 32 strains which showed 20 mm or more in DIZD were included for study. The results were as follows. 1) About 70% of 98 strains of S. pneumoniae were serotyped by 6 kinds of antisera. Among penicillin-susceptible S. pneumoniae (PSSP), type 3 were 20.6%, type 19, 15.9%, type 6, 14.3%, type 18, 9.5%, type 14, 7.9%, and type 4, 1.6%. Among penicillin-intermediate S. pneumoniae (PISP), and penicillin-resistant S. pneumoniae (PRSP), type 19 were 60%, and type 18, 8.6%. In PISP and PRSP, more than half were type 19, which indicates they are distinctly different from PSSP in serotypical distribution. 2) As to the difference between screening by MPIPC disk and minimum inhibitory concentration (MIC) by benzylpenicillin (PCG), among 66 MPIPC resistant strains, PSSP strains were 31 in number (47%). 3) MIC showed that PISP and PRSP strains were more resistant than PSSP against cefaclor (CCL), cefazolin (CEZ), cefotiam (CTM), cefotaxime (CTX), imipenem (IPM), minocycline (MINO), and erythromycin (EM), but no difference was found in the 2 groups of strains in MIC with clindamycin (CLDM) and ofloxacin (OFLX). 4) All type 3 strains formed mucoid colonies and were resistant to MINO and highly resistant to EM and CLDM. 5) By NCCLS, category of antimicrobial susceptibility is determined against CCL, EM, OFLX, in MD method and K-B method. Against these antibiotics, the complete agreement rates were 75.8%, 92.4% and 86.4% respectively.

Cefaclor↗

Antimicrobial activity of Ro 15-8074, active metabolite of a new oral cephalosporin (Ro 15-8075), against 7,775 recent clinical isolates.

Susceptibility testing of 7,775 recent clinical isolates from four medical centers showed Ro 15-8074 to be 2-to greater than 8-fold more active than either cefaclor or cefuroxime against the Enterobacteriaceae. Ro 15-8074 MICs for 50% of the strains tested were greater than or equal to 32 micrograms/ml for Staphylococcus spp., enterococci, Pseudomonas aeruginosa, and Pseudomonas maltophilia. beta-Lactamase hydrolysis experiments failed to demonstrate significant Ro 15-8074 inactivation by commonly encountered chromosomal or plasmid-mediated enzymes (P99, K1, K14, TEM, and CARB).

Anti-Bacterial Agents↗

In vitro activity of BMY-28100, a new oral cephalosporin.

The activity of BMY-28100, a new orally administered cephalosporin, was compared with those of cephalexin and cefaclor. BMY-28100 was the most active drug against Staphylococcus aureus (MIC for 90% of strains tested [MIC90], 1.0 microgram/ml), streptococci (MIC90S, less than or equal to 0.125 microgram/ml), and Klebsiella pneumoniae (MIC90, 2 micrograms/ml). The drug was active against Haemophilus influenzae and gonococci but not against other organisms generally resistant to cephem antibiotics.

Anti-Bacterial Agents↗

In vitro and in vivo antibacterial activities of T-2588, a new oral cephalosporin, compared with those of other oral beta-lactam antibiotics.

T-2588, the pivaloyloxymethyl ester of T-2525, [6R, 7R]-7-[(z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetoamido] -3- [(5-methyl-2H-tetrazol-2-yl)methyl]-3-cephem-4-carboxylic acid, is a new oral cephalosporin. T-2525 had a widely expanded antibacterial spectrum against gram-negative and gram-positive bacteria. T-2525 was more active in vitro than cefaclor, cephalexin, and amoxicillin against members of the family Enterobacteriaceae and Branhamella catarrhalis. Moreover, it exhibited superior in vitro activity against Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria gonorrhoeae. T-2525 was highly stable to various beta-lactamases, which were classified as Richmond and Sykes types Ia, Ib, Ic, III, IV, and Vc. It had high affinities for the lethal (essential) penicillin-binding proteins of Escherichia coli, Clostridium perfringens, and Bacteroides fragilis. T-2588 had excellent therapeutic effect on systemic infections in mice with various species of gram-negative bacteria, including beta-lactamase-producing bacteria.

Amoxicillin↗

National collaborative study of the prevalence of antimicrobial resistance among clinical isolates of Haemophilus influenzae.

A total of 2,811 clinical isolates of Haemophilus influenzae were obtained during 1986 from 30 medical centers and one nationwide private independent laboratory in the United States. Among these, 757 (26.9%) were type b strains. The overall rate of beta-lactamase-mediated ampicillin resistance was 20.0%. Type b strains were approximately twice as likely as non-type b strains to produce beta-lactamase (31.7 versus 15.6%). The MICs of 12 antimicrobial agents were determined for all isolates. Ampicillin resistance among strains that lacked beta-lactamase activity was extremely uncommon (0.1%). Percentages of study isolates susceptible to cefamandole, cefaclor, cephalothin, and cephalexin were 98.7, 94.5, 87.3, and 43.3%, respectively. For 14 strains (0.5% of the total), chloramphenicol MICs were greater than or equal to 8.0 micrograms, and thus the strains were considered resistant. All of these resistant strains produced chloramphenicol acetyltransferase. In addition, all 14 strains were resistant to tetracycline; 11 produced beta-lactamase. The percentage of isolates susceptible to tetracycline was 97.7%. In contrast, erythromycin and sulfisoxazole were relatively inactive. The combination of erythromycin-sulfisoxazole (1/64) was more active than erythromycin alone but essentially equivalent in activity to sulfisoxazole alone. Finally, small numbers of clinical isolates of H. influenzae were resistant to trimethoprim-sulfamethoxazole and rifampin.

Ampicillin Resistance↗

In vitro antibacterial activity and beta-lactamase stability of SY5555, a new oral penem antibiotic.

The antibacterial activity of SY5555, a new oral penem antibiotic, was compared with those of cefaclor, cefixime, and cefteram. SY5555 was more active than the comparison agents against methicillin-susceptible Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Enterococcus faecalis, Citrobacter freundii, Enterobacter cloacae, Morganella morganii, Acinetobacter calcoaceticus, Clostridium spp., and Bacteroides fragilis. Against Providencia spp., Proteus spp., and Haemophilus influenzae, SY5555 was less active than cefixime or cefteram. SY5555 was inactive against methicillin-resistant S. aureus. Enterococcus faecium, Serratia marcescens, Pseudomonas aeruginosa, and Xanthomonas maltophilia, as were the comparison agents. The bactericidal activities of SY5555, cefixime, and cefteram were at or slightly greater than the MICs for clinical isolates of Escherichia coli and Klebsiella pneumoniae. SY5555 was not hydrolyzed by various types of beta-lactamases. However, SY5555 and the comparison agents were hydrolyzed by X. maltophilia (L-1) and P. aeruginosa/pMS354 beta-lactamases, two Bush group 3 beta-lactamases, SY5555 showed a high affinity, as did cefixime and cefteram, for cephalosporinases from C. freundii GN7391 and E. cloacae GN7471 strains. These results suggest that SY5555 may be more specific than existing beta-lactam antibiotics.

Administration, Oral↗

Comparative antimicrobial activities of the penem WY-49605 (SUN5555) against recent clinical isolates from five U.S. medical centers.

The in vitro activity of WY-49605 (SUN5555) (WY) was compared with those of cefaclor, cefixime, and amoxicillin-clavulanic acid against 2,958 consecutive clinical isolates from five medical centers and 402 respiratory pathogens from 18 other facilities. Most members of the family Enterobacteriaceae were inhibited by WY (MIC at which 50% of the isolates are inhibited [MIC50], < or = 2.0 micrograms/ml). MIC90s of > or = 8.0 micrograms/ml were observed for Enterobacter cloacae, Serratia spp., and Proteus mirabilis. WY was the most active drug against methicillin-susceptible Staphylococcus aureus (MIC90, 0.12 microgram/ml) and other coagulase-negative staphylococci (MIC90, 4.0 micrograms/ml). The four drugs were not active against nonenteric gram-negative bacilli, methicillin-resistant Staphylococcus aureus, and Staphylococcus haemolyticus. At 2.0 micrograms/ml, WY inhibited 82% of Enterococcus faecalis strains and was equal to or superior to the other drugs against streptococci, Haemophilus influenzae, and Moraxella catarrhalis.

Amoxicillin↗

Disk diffusion susceptibility testing for LY163892 (KT-3777), a new orally administered 1-carbacephem.

LY163892, a new orally administered 1-carbacephem, was found to have a spectrum of antimicrobial activity very similar to that of cefaclor. Diffusion tests with 30-micrograms LY163892 disks produced acceptable interpretive error rates with greater than or equal to 22 mm as the susceptibility zone diameter. This was required to reduce potential false-susceptibility results, particularly among Enterobacter spp. and Providencia stuartii: both species included strains that produce beta-lactamases capable of hydrolyzing Ly163892. Preliminary recommendations for LY163892 disk tests are presented, but the continued use of the 30-micrograms cephalothin "class representative" disk might be the best procedure to minimize LY163892 interpretive errors for clinical trials. A separate LY163892 disk for testing Haemophilus influenzae strains should be seriously considered.

Bacteria↗

Sporotrichoid pyogenic bacterial infection.

Two cases of pyogenic bacterial infection, which initially resembled lymphocutaneous sporotrichosis are reported. In case 1, Staphylococcus aureus and Streptococcus group A were cultured from the lesion and in case 2, S. aureus alone. Histologically, botryomyotic grains were identified in case 2; this patient had diffuse normolipidemic plane xanthoma. With oral administration of cefaclor, the cutaneous lesions dramatically improved in both cases.

Adult↗

Effect of erythromycin on endotoxin-induced microvascular leakage in the rat trachea and lungs.

To determine whether the macrolide antibiotic erythromycin prevents microvascular leakage produced by lipopolysaccharide (LPS), we studied tracheae and lungs of pathogen-free rats. Tracheal vascular permeability and neutrophil recruitment were assessed by the percent area occupied by Monastral blue-labeled blood vessels and by myeloperoxidase-containing granulocytes, respectively, in tracheal whole mounts. Pulmonary microvascular leakage was evaluated by lung wet-to-dry (W/D) weight ratio. Inhalation of Escherichia coli LPS (5 mg/kg) caused time-dependent increases in tracheal vascular permeability, neutrophil influx, and lung W/D ratio. These responses were inhibited by pretreatment with oral erythromycin, but not by ampicillin or cefaclor, in a dose-dependent manner: erythromycin at 10 mg/kg daily for 1 wk reduced the area density of Monastral blue-labeled vessels from 6.7 +/- 1.2 to 1.4 +/- 0.3% (p < 0.01), the number of neutrophils (from 365 +/- 51 to 149 +/- 30 cells/mm2, p < 0.01), and lung W/D weight ratio (from 6.76 +/- 0.30 to 5.39 +/- 0.21, p < 0.01). This inhibitory effect of erythromycin was abolished by depletion of circulating neutrophils with cyclophosphamide. These results suggest that LPS causes acute lung injury, microvascular leakage, and neutrophil recruitment in the trachea, and that erythromycin protects against these changes, probably by acting on neutrophils.

Ampicillin↗

Antimicrobial treatment of otitis media: penicillins, cephalosporins, sulfonamides.

Otitis media continues to be one of the most common diagnoses made in the offices of family physicians, pediatricians, and otolaryngologists. The emergence of ampicillin resistant Hemophilus influenzae as an important etiologic agent for otitis media has altered the selection of a therapeutic antimicrobial drug. This article reviews the role of the penicillins, cephalosporins, and sulfonamides in the treatment of otitis media. Amoxicillin continues to be the drug chosen for the uncultured otitis media. Backup drugs for use in unresponsive cases include trimethoprim-sulfamethoxazole, erythromycin-sulfisoxazole, and cefaclor. The cost of the drug should be a factor in the selection when efficacy is equal.

Acute Disease↗

Sensitivity of Branhamella catarrhalis to oral antibiotics.

B. catarrhalis is a potential pathogen in the upper and lower respiratory tract which has been implicated as a clinically important cause of chronic bronchitis and otitis media in children. Since the late 1970s the proportion of B. catarrhalis strains elaborating beta-lactamase seems to have significantly increased; some centres are now reporting prevalence rates as high as 76%. Such a dramatic increase in the number of beta-lactamase positive strains is of clinical importance when assessing the indirect pathogenic potential of B. catarrhalis and when selecting suitable antimicrobial therapy. Early studies showed that B. catarrhalis was sensitive to penicillin V with a MIC90 of 1.2 mg/L while, more recently, MIC90 values of 2.0 mg/L have been noted. Ampicillin and, perhaps surprisingly, cefaclor are also inactivated by some beta-lactamase-producing strains of B. catarrhalis. A majority of strains of B. catarrhalis is susceptible to erythromycin (MIC90 0.15 to 0.5 mg/L) and tetracyclines (especially doxycycline, MIC90 0.25 to to 0.5 mg/L). Co-trimoxazole also seems to be effective against most isolates of B. catarrhalis whereas trimethoprim alone is relatively ineffective.

Administration, Oral↗

Activity of common antibiotics against Branhamella catarrhalis, Haemophilus influenzae, pneumococci, group A streptococci and Staphylococcus aureus in 1983.

The activity of phenoxymethylpenicillin (PcV), ampicillin, cefaclor, cefuroxime, chloramphenicol, co trimoxazole, doxycycline and erythromycin against clinical isolates of Branhamella catarrhalis, Haemophilus influenzae, pneumococci, group A streptococci and Staphylococcus aureus in 1983 was investigated with the MIC-method (plate-dilution technique). Forty-six percent of B. catarrhalis, 2% of H. influenzae and 78% of S. aureus were beta-lactamase producing and had high MIC-values for penicillin and ampicillin. Thus MIC for 90% of all strains of B. catarrhalis was 32 mg/l and 8 mg/l for penicillin and ampicillin while MIC for 90% of non beta-lactamase producing Branhamella strains was 2 mg/l and 0.25 mg/l respectively. This indicates a high susceptibility of penicillins to the action of Branhamella beta-lactamase. Almost all strains of B. catarrhalis, pneumococci, group A streptococci and S. aureus were inhibited at low concentrations of erythromycin. However, 4 mg/l was required to inhibit 90% of H. influenzae. Co-trimoxazole and doxycycline had good activity against all B. catarrhalis and H. influenzae strains while a few pneumococci, streptococci and staphylococci had intermediate sensitivity or were resistant. Essentially all strains were sensitive to cefuroxime and chloramphenicol.

Ampicillin↗

[Factors on delayed recovery of otitis media with effusion in children--clinical and bacteriological study].

The resolution of middle ear effusions (MEE) of children with otitis media with effusion (OME) who underwent myringotomy for the bacteriological examination was analyzed in terms of the culture results and the clinical features. The present study consisted of 193 children (258 ears), and the MEE from 77 ears (30%) were culture positive and the respiratory pathogens were detected from 44 ears (17%). Each child was then assigned to receive either a more than two-week course of antibiotics, cefaclor (CCL) or not. At one month following entry, 53 (55%) out of 97 ears in CCL-treated group were effusion-free compared with 31 (40%) out of 78 ears in the control group (P less than 0.05). In the control group, the resolution of MEE was significantly poor in the recurrent cases and the cases with pathogen positive-MEE. The presence of accompanying diseases such as adenoid vegetation, chronic sinusitis and allergy, however, was not related to the resolution of MEE. On the other hand, the cure rate of the cases with pathogen positive-MEE and recurrent cases in the CCL-treated group showed significant improvement. Furthermore, the cases accompanying adenoid vegetation and chronic sinusitis tended to become effusion-free after the antibiotic treatment. Therefore, the persistent bacterial infection in the middle ear and/or surrounding organs such as adenoid plays possibly an important role in the delayed recovery of OME. Antibiotics treatment could increase, to some extent, the resolution of MEE in cases with OME.

Adolescent↗