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PubMed2003

Phenotypes of macrolide resistance of group A streptococci isolated from outpatients in Bavaria and susceptibility to 16 antibiotics.

The purpose of the present study was to determine the antimicrobial resistance among Streptococcus pyogenes in Bavaria, Germany. Five hundred and forty isolates of S. pyogenes were collected from patients with tonsillopharyngitis. Of these, 425 isolates were obtained from children and 115 from adult patients. All isolates were tested for susceptibility to macrolides, clindamycin, penicillin and 10 other commonly prescribed antimicrobial agents, using broth microdilution tests. All isolates were fully susceptible to penicillin, amoxicillin and cephalosporins; 16.1% of the isolates were resistant to tetracycline. MIC(90) values of erythromycin, clarithromycin, azithromycin and josamycin were 16, 4, 16 and 0.5 mg/L. The overall resistance rate of S. pyogenes to erythromycin, clarithromycin and azithromycin was 13.3%. All isolates resistant to erythromycin were also resistant to clarithromycin and azithromycin, and vice versa. Erythromycin resistance rates were higher in adult patients (19.1%) than in children (11.8%). The resistance rate to josamycin was only 1.5%, a value similar to that of clindamycin (1.1%). Among the 72 erythromycin-resistant isolates the M phenotype of macrolide resistance predominated (78%), while percentages of cMLS(B) (8%) and iMLS(B) (14%) phenotypes were low. Of the iMLS(B) strains (n = 10), the majority were of the subtype C (n = 8). The M phenotype was associated with a low, and the iMLS(B)-C phenotype with a high, rate of resistance to tetracycline. Conclusively, present data point to rising macrolide resistance among S. pyogenes in Bavaria.

Anti-Bacterial Agents↗

PubMed2003

Acquired macrolide resistance genes and the 1 bp deletion in the mtrR promoter in Neisseria gonorrhoeae.

The presence of macrolide-lincosamide-streptogramin B resistance genes erm(B), erm(C) and erm(F), the macrolide resistance mef(A) gene, and the DNA sequence of a 13 bp repeat in the promoter region of the mtrR gene, were determined in 62 Neisseria gonorrhoeae isolates collected between 1992 and 1999 in Seattle, Washington, USA. Eleven isolates with erythromycin and azithromycin MICs of < or =0.06 mg/L, had no acquired genes or deletions in the 13 bp repeat region. Among 44 isolates with erythromycin MICs 1.0-16.0 mg/L, and azithromycin MICs 0.06-4.0 mg/L, 16 carried the 1 bp deletion in the mtrR promoter region alone, nine carried one or more of the four acquired macrolide resistance genes alone, and 14 carried both acquired macrolide resistance genes plus the 1 bp deletion in the mtrR promoter region. Three isolates with erythromycin MICs > or = 8 mg/L, and azithromycin MICs of 4.0 mg/L, carried only erm genes. Five isolates with MICs of 1-2 mg/L did not carry the 1 bp deletion, or any of the acquired resistance genes examined. Our data suggest that the 1 bp deletion in the mtrR promoter region is not found in all erythromycin-resistant (MIC > or = 1.0 mg/L) N. gonorrhoeae.

Anti-Bacterial Agents↗

PubMed2004

Antimicrobial susceptibility of Haemophilus influenzae strains isolated from invasive disease in Italy.

OBJECTIVES: Haemophilus influenzae invasive disease is potentially life threatening and requires prompt antibiotic therapy. The aim of this study was to assess the antimicrobial susceptibility of H. influenzae strains isolated from invasive disease in Italy and to investigate ampicillin-resistant isolates by molecular biology techniques. MATERIALS AND METHODS: One-hundred and seventy-six invasive H. influenzae isolates, collected during 1998-2003, were analysed for susceptibility to ampicillin, azithromycin, chloramphenicol and ciprofloxacin. Ampicillin-resistant isolates were further tested against cefotaxime and imipenem. MICs were determined by Etest and interpreted according to NCCLS criteria. The ampicillin resistance genes, bla(TEM) and bla(ROB), were searched for by PCR. Genetic relatedness among ampicillin-resistant isolates was investigated by PFGE. RESULTS: Overall, ampicillin resistance was 10.2% (all beta-lactamase producer strains). The prevalence of ampicillin-resistant isolates increased from 6.9% in 1998/1999 to 19% in 2002/2003. Resistance to azithromycin and chloramphenicol was 6.8% and 1.7%, respectively. No strains were resistant to ciprofloxacin. Co-resistance between ampicillin and chloramphenicol and between ampicillin and azithromycin was observed in three and one isolates, respectively. All ampicillin-resistant isolates were susceptible to cefotaxime and imipenem and all harboured the bla(TEM) gene. PFGE demonstrated that most of the ampicillin-resistant isolates showed little genetic homology. CONCLUSIONS: An upward trend in resistance to ampicillin due to beta-lactamase production was demonstrated In Italy. According to PFGE results, clonal dissemination of ampicillin-resistant isolates does not occur. Imipenem may represent an appropriate alternative for treatment of H. influenzae invasive disease caused by ampicillin-resistant isolates when third-generation cephalosporins cannot be used.

Adolescent↗

PubMed2005

Citywide emergence of Pseudomonas aeruginosa strains with reduced susceptibility to polymyxin B.

OBJECTIVES: To determine the prevalence of Pseudomonas aeruginosa isolates with reduced susceptibility to polymyxin B, and to assess the in vitro activity of antibiotic combinations. METHODS: All unique patient isolates of P. aeruginosa were collected from 11 Brooklyn, NY hospitals during a three month period in 2003. Isolates with reduced susceptibility to polymyxin B (MIC > 2 mg/L) underwent ribotyping. The activity of polymyxin B combined with rifampicin, azithromycin and/or imipenem was tested by the chequerboard and time-kill methods against a subset of isolates. RESULTS: Of 527 isolates, only 61% were susceptible to imipenem. Twenty-five isolates (5%), from 8/11 hospitals, had reduced susceptibility to polymyxin B (MICs 4-8 mg/L), compared with 0/691 isolates collected in 2001. Ten of 25 were resistant to multiple other antibiotic classes. Ribotyping of the isolates revealed 19 unique types. Chequerboard testing of the 10 multiresistant isolates demonstrated synergy for the combinations of polymyxin B with azithromycin, imipenem and rifampicin in 6, 2, and 1 isolates, respectively. Time-kill studies revealed bactericidal activity for the following antibiotics when combined with polymyxin B: imipenem plus rifampicin against all 10 isolates, rifampicin in 9/10 isolates, imipenem in 8/10 isolates and azithromycin in 4/10 isolates. MICs of bacteria surviving incubation in polymyxin B alone rose for 4/9 isolates (MIC range 12-48 mg/L). CONCLUSIONS: P. aeruginosa with reduced susceptibility to polymyxin B have emerged in multiple strains in Brooklyn, NY. Combinations of polymyxin B with rifampicin and/or imipenem are bactericidal. The clinical utility of these combinations remains to be determined.

Anti-Bacterial Agents↗

PubMed2003

Antimicrobial susceptibility of Neisseria gonorrhoeae in Cuba (1995-1999): implications for treatment of gonorrhea.

BACKGROUND: Antibiotic-resistant strains of Neisseria gonorrhoeae, especially those resistant to penicillin and tetracycline, have spread with remarkable rapidity in many Caribbean countries. GOAL: The goal of the study was to survey the antibiotic susceptibilities of N gonorrhoeae strains isolated from 1995 to 1999 in Cuba and to discuss the impact of antimicrobial resistance on the management of gonorrhea in the country. STUDY DESIGN: Susceptibility of the strains to penicillin, tetracycline, cefuroxime, ceftriaxone, ciprofloxacin, spectinomycin, and azithromycin were determined by an agar dilution method. RESULTS: Penicillin and tetracycline resistance was noted in 60.8% and 54.2%, respectively, of the N gonorrhoeae strains tested. A total of 63.35 (76/120) of the N gonorrhoeae strains exhibited plasmid-mediated resistance to penicillin, tetracycline, or both. Strains with chromosomally mediated resistance to these antibiotics accounted for 10% (12/120) of the strains. The strains were susceptible to ceftriaxone, cefuroxime, spectinomycin, and ciprofloxacin. One strain's ciprofloxacin MIC was 0.125 mircog/ml. Of the 52 strains tested, 23.1% displayed intermediate resistance to azithromycin. CONCLUSIONS: N gonorrhoeae strains exhibited a high frequency of resistance and multiresistance to penicillin and tetracycline. Therefore, these antibiotics should no longer be used to treat gonococcal infections in Cuba and should be substituted with effective drugs such as third-generation cephalosporins, spectinomycin, and fluoroquinolones. The detection of intermediate resistance to azithromycin and ciprofloxacin underlines the importance of periodic surveillance for susceptibility of N gonorrhoeae strains to antimicrobials agents used as primary therapy for gonorrhea.

Anti-Bacterial Agents↗

PubMed2003

Antimicrobial susceptibilities of Neisseria gonorrhoeae strains isolated in Java, Indonesia.

BACKGROUND: Despite the rapid spread of antibiotic resistance in gonococci all over Southeast Asia, there is only limited surveillance for antibiotic susceptibility in Indonesia. GOAL: This study was undertaken to determine the frequency and diversity of antimicrobial resistance in gonococcal isolates from cohorts of female commercial sex workers in Bandung and Jakarta, Indonesia, and to characterize the Tet M plasmid among the tetracycline-resistant strains N gonorrhoeae. STUDY DESIGN: The antimicrobial susceptibility of 267 strains (85 strains from Bandung and 182 from Jakarta) to penicillin, spectinomycin, tetracycline, ciprofloxacin, cefotaxime, thiamphenicol, kanamycin, azithromycin, and trimethoprim-sulfamethoxazole (TMP-SMZ) was determined by agar dilution. Typing of the Tet M plasmid in tetracycline-resistant isolates was performed by PCR. RESULTS: Prevalence of penicillin and tetracycline resistance was extremely high: 60.0% of the isolates from Bandung and 70.9% of the isolates from Jakarta were resistant to penicillin. Of these, 60.0% and 62.1%, respectively, were penicillinase-producing N gonorrhoeae (PPNG). All the isolates from Bandung and 98.4% from Jakarta were resistant to tetracycline. All tetracycline-resistant isolates from Bandung and 97.8% from Jakarta carried a PCR fragment characteristic of the "Dutch" type Tet M plasmid. One isolate from Jakarta showed chromosomal resistance to tetracycline (0.6%). Chromosomal resistance to thiamphenicol (MIC, >/=2.0 microg/ml) was significantly higher in Jakarta than in Bandung (P < 0.05). All gonococcal isolates were susceptible to kanamycin, spectinomycin, cefotaxime, ciprofloxacin, and azithromycin. CONCLUSION: Spectinomycin, fluoroquinolones, and azithromycin are still useful primary drugs for treatment of gonococcal infections in Indonesia. Continued surveillance of antimicrobial susceptibility should be part of gonorrhea control in Indonesia.

Anti-Bacterial Agents↗

PubMed2002

Prevalence of resistant Helicobacter pylori isolates in Bulgarian children.

The aim of this study was to assess the primary and combined resistances of Helicobacter pylori isolates obtained from paediatric patients in 2000-2001 to seven antimicrobial agents. Resistance rates of pre-treatment isolates from 115 children were investigated by the limited agar dilution method alone and by the E-test. The cut-off concentrations for resistance were: metronidazole >8 mg/L, clarithromycin and azithromycin >1 mg/L, clindamycin >4 mg/L, amoxicillin >0.5 mg/L, tetracycline >4 mg/L and ciprofloxacin >1 mg/L. Primary resistance rates were: metronidazole 15.8%, clarithromycin 12.4%, azithromycin 14.6%, clindamycin 20.0%, amoxicillin 0%, metronidazole + clarithromycin 4.5%, ciprofloxacin 6.0%, metronidazole + clarithromycin + ciprofloxacin 1.2%, tetracycline 3.1% and metronidazole + ciprofloxacin 1.2%. There were no significant age (1-9 years versus 10-18 years) or gender differences. Prevalence of both macrolide-resistant and intermediately susceptible strains was 21.9% for azithromycin and 15.9% for clarithromycin. Of 18 metronidazole-resistant isolates, 77.8% exhibited a metronidazole MIC > or = 32 mg/L. H. pylori resistance rates to metronidazole, clarithromycin and both agents were relatively low in Bulgarian children. However, resistance was found to all drugs tested except for amoxicillin. The consumption of newer macrolides and tetracyclines could be related to the prevalence of resistance to the corresponding agents. There were no significant differences in primary resistance rates of H. pylori to antimicrobial agents between children and adults except for metronidazole. Multi-drug resistance to newer macrolides, metronidazole and ciprofloxacin in association with a slightly elevated amoxicillin MIC (0.38 mg/L) was detected in one strain.

Adolescent↗

PubMed1998

Comparative susceptibilities of various AIDS-associated and human urogenital tract mycoplasmas and strains of Mycoplasma pneumoniae to 10 classes of antimicrobial agent in vitro.

The susceptibilities of 40 strains of various Mycoplasma species to 10 classes of antimicrobial agents were compared in vitro by a broth microdilution method. The strains tested comprised 20 strains of four AIDS-associated species--M. penetrans (1 strain), M. fermentas (5 strains), M. pirum (6 strains) and M. genitalium (8 strains)--nine strains of the urogenital tract species M. hominis and 11 strains of M. pneumoniae. The results demonstrated wide variation in the susceptibilities of the different Mycoplasma spp. to different classes of antimicrobial agent. All the mycoplasmas were susceptible or highly susceptible to the fluoroquinolones, with sparfloxacin the most active, and to the diterpine antibiotic tiamulin. M. pneumoniae and M. genitalium strains were also highly susceptible to the macrolides, particularly azithromycin and had similar antibiotic susceptibility patterns to most other antimicrobial agents. However, all strains of M. genitalium were resistant to streptomycin (MIC 250->500 mg/L) whereas all M. pneumoniae isolates, except the MAC strain, were susceptible (MICs 1.25-12.5 mg/L). M. pirum isolates varied considerably in their susceptibility to macrolides (MIC range versus azithromycin 0.0025->100 mg/L). M. fermentans strains were susceptible to the tetracyclines, lincosamides and mupirocin, but varied in susceptibility to aminoglycosides. Most M. hominis strains were susceptible to the tetracyclines and all were susceptible to clindamycin and mupirocin. M. penetrans GTU 54 was susceptible to azithromycin, the tetracyclines and lincosamides as well as to the fluoroquinolones and tiamulin.

AIDS-Related Opportunistic Infections↗

PubMed2004

Antimicrobial susceptibility of Enterococcus faecalis isolated from canals of root filled teeth with periapical lesions.

AIM: To test, in vitro, the susceptibility to different antibiotics of Enterococcus faecalis isolates from canals of root filled teeth with periapical lesions. METHODOLOGY: Twenty-one E. faecalis isolates, from canals of root filled teeth with persisting periapical lesions, were tested for their antibiotic susceptibilities. The following antibiotics were used: benzylpenicillin, amoxicillin, amoxicillin-clavulanic acid, erythromycin, azithromycin, vancomycin, chloramphenicol, tetracycline, doxycycline, ciprofloxacin and moxifloxacin. Minimal inhibitory concentrations (MICs) for the antimicrobial agents were determined using the E-test System (AB BIODISK, Solna, Sweden), and the E. faecalis strains classified as susceptible or resistant according to the guidelines of National Committee for Clinical Laboratory Standards (NCCLS). The strains were also tested for beta-lactamase production with nitrocefin (Oxoid, Basingstoke, UK). RESULTS: All strains were susceptible to penicillins in vitro, however, the MICs of amoxicillin and amoxicillin-clavulanic acid (MIC(90) = 0.75 microg mL(-1)) were lower than for benzylpenicillin (MIC(90) = 3.0 microg mL(-1)). All strains studied were also susceptible to vancomycin and moxifloxacin, whilst 95.2% were susceptible to chloramphenicol. Amongst the isolates, 85.7% were susceptible to tetracycline and doxycycline and 80.9% to ciprofloxacin. The MIC of erythromycin ranged from 0.38 to >256 microg mL(-1); only 28.5% of the strains were susceptible (MIC < or = 0.5 microg mL(-1)). Limited susceptibility was also observed with azithromycin which was active against only 14.2% of isolates. No strains produced beta-lactamase. CONCLUSION: Enterococcus faecalis isolates were completely susceptible, in vitro, to amoxicillin, amoxicillin-clavulanic acid, vancomycin and moxifloxacin. Most isolates were susceptible to chloramphenicol, tetracycline, doxycycline or ciprofloxacin. Erythromycin and azithromycin were least effective.

Anti-Bacterial Agents↗

PubMed2004

Antimicrobial susceptibility to levofloxacin and other antibacterial agents among common respiratory pathogens-a Brazilian perspective from the GLOBAL Surveillance Initiative 2001-2002.

The GLOBAL (Global Landscape On Bactericidal Activity of Levofloxacin) Surveillance programme monitored antimicrobial susceptibility patterns of the key respiratory tract pathogens Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis collected in Brazil during 1997-1998, 1999-2000 and 2001-2002. Penicillin and azithromycin resistance among S. pneumoniae strains increased from 1997-1998, reaching 7.9% and 9.5%, respectively, in 2001-2002. Although decreasing by 4.9% since the previous study, trimethoprim-sulphamethoxazole resistance remained high at 33.7%. Concurrent resistance to penicillin, azithromycin and trimethoprim-sulphamethoxazole was seen in 2.9% of the S. pneumoniae isolates collected. Levofloxacin remained extremely active against S. pneumoniae, with 0.3% resistance reported in 1997-1998 and 0% resistance in 1999-2000 and 2001-2002. beta-Lactamase production in H. influenzae was > 10% in all three studies, with correspondingly high rates of ampicillin resistance. Trimethoprim-sulphamethoxazole was the least active agent tested against H. influenzae, with resistance rates of > 40% recorded in all three studies. All H. influenzae isolates were susceptible to cefuroxime, ceftriaxone, azithromycin and levofloxacin. Of the M. catarrhalis isolates, 98.0% in 1997-1998, 98.0% in 1999-2000 and 81.8% in 2001-2002 were beta-lactamase-positive. The continued high prevalence of antimicrobial resistance in Brazil underscores the importance of current surveillance initiatives. Levofloxacin, a fluoroquinolone prescribed widely for respiratory tract infections, continued to show potent activity against key respiratory pathogens.

Anti-Bacterial Agents↗

PubMed1988

Comparative in vitro activities of new 14-, 15-, and 16-membered macrolides.

The in vitro activities of several 14-, 15- and 16-membered macrolides were compared with that of erythromycin. In general, 14-membered macrolides such as erythromycin, clarithromycin, and flurithromycin were more active against streptococci and Bordetella pertussis than was the 15-membered macrolide azithromycin, which was more active than 16-membered macrolides such as miocamycin and rokitamycin. Clarithromycin was the most active compound against Streptococcus pyogenes, pneumococci, Listeria monocytogenes, and Corynebacterium species. Legionella pneumophila was most susceptible to miocamycin, clarithromycin, and rokitamycin. Branhamella catarrhalis, Neisseria gonorrhoeae, and Haemophilus influenzae were most susceptible to azithromycin. Azithromycin and dirithromycin were the most active compounds against Campylobacter jejuni. MICs of 16-membered macrolides for strains expressing inducible-type resistance to erythromycin were less than or equal to 1 microgram/ml, whereas none of the compounds had activity against strains expressing constitutive-type resistance. The MICs of roxithromycin, miocamycin, rokitamycin, and josamycin increased in the presence of human serum, whereas MICs of the other compounds either were unchanged or decreased.

Aminoglycosides↗

PubMed1995

Susceptibilities of Chlamydia trachomatis isolates causing uncomplicated female genital tract infections and pelvic inflammatory disease.

The in vitro susceptibilities of 45 recent clinical isolates of Chlamydia trachomatis obtained from women with asymptomatic genital tract infection, mucopurulent cervicitis, or pelvic inflammatory disease to doxycycline, azithromycin, ofloxacin, and clindamycin were determined. In addition, susceptibilities of 12 isolates to amoxicillin and trimethoprim-sulfamethoxazole were also determined. Isolates also were serotyped with a panel of monoclonal antibodies specific for chlamydial major outer membrane protein; 24 of 45 (53%) belonged to serovars Ia and E. For all isolates, the MIC range of doxycycline was 0.008 to 0.06 micrograms/ml, for trimethoprim-sulfamethoxazole it was 0.03 to 0.25 micrograms/ml, for azithromycin it was 0.125 to 2.0 micrograms/ml, for ofloxacin it was 0.5 to 1.0 micrograms/ml, for clindamycin it was 0.25 to 2.0 micrograms/ml, and for amoxicillin it was 0.25 to 4.0 microgram/ml. The ranges of minimum chlamydiacidal concentrations were generally 1 to 4 dilutions above the MICs of most agents, with a rank order similar to those of the MICs. Comparing the minimum chlamydiacidal concentrations for 90% of isolates tested, isolates causing asymptomatic infection belonged to a greater variety of serovars and were relatively more susceptible to doxycycline and azithromycin than isolates causing mucopurulent cervicitis or pelvic inflammatory disease; these differences in susceptibility were not detected among the other study agents. These data indicate that additional studies are needed to better define the apparent association of certain chlamydial serovars with the clinical severity of disease and the in vitro susceptibilities to certain antimicrobial agents.

Anti-Bacterial Agents↗

PubMed1997

Antibiotic resistance among clinical isolates of Haemophilus influenzae in the United States in 1994 and 1995 and detection of beta-lactamase-positive strains resistant to amoxicillin-clavulanate: results of a national multicenter surveillance study.

A total of 1,537 clinical isolates of Haemophilus influenzae were recovered in 30 U.S. medical center laboratories between 1 November 1994 and 30 April 1995 and were characterized in a central laboratory with respect to serotype and beta-lactamase production and the in vitro activities of 15 oral antimicrobial agents. Overall, 36.4% of the isolates were found to produce beta-lactamase. The rank order of activity of six cephalosporins on the basis of MICs was cefixime > cefpodoxime > cefuroxime > loracarbef > or = cefaclor > cefprozil. On the basis of current National Committee for Clinical Laboratory Standards (NCCLS) breakpoints ages of isolates found to be resistant or intermediate to these agents were as follows: 0.1, 0.3, 6.4, 16.3, 18.3, and 29.8, respectively (National Committee for Clinical Laboratory Standards. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically, 4th ed. M7-A4, 1995). Azithromycin was, on a weight basis, the most potent of the macrolides tested in this study, followed by erythromycin and then clarithromycin. Azithromycin was typically fourfold more active than erythromycin, which was, in turn, slightly more active than clarithromycin. However, when compared on the basis of the frequency of resistance determined by using current NCCLS breakpoints, there was essentially no difference between azithromycin and clarithromycin, i.e., 0.5 and 1.9%, respectively (P = 0.086). Interpretive breakpoints for erythromycin MIC tests versus H. influenzae have not been developed. Resistance to other non- beta-lactam agents was variable, as follows: trimethoprim-sulfamethoxazole, 9.0%; chloramphenicol, 0.2%; tetracycline, 1.3%; and rifampin, 0.3%. Two conspicuous findings in this study were the identification of 39 strains H. influenzae that were beta-lactamase negative but ampicillin intermediate or resistant (BLNAR) and, even more surprisingly, 17 beta-lactamase-positive isolates that were resistant to amoxicillin-clavulanate (BLPACR). Strains of H. influenzae in the first group have heretofore been very uncommon; organisms in the second group have not previously been described in the literature. The percentages of all study isolates comprised of BLNAR and BLPACR organisms were 2.5 and 1.1, respectively. Overall resistance to ampicillin was thus 38.9%, and that to amoxicillin-clavulanate was 4.5%.

Adolescent↗

PubMed1999

In vitro susceptibilities of Chlamydia pneumoniae isolates from German patients and synergistic activity of antibiotic combinations.

The susceptibilities of six Chlamydia pneumoniae type strains and of six German patient isolates to erythromycin, azithromycin, roxithromycin, clarithromycin, doxycycline, ofloxacin, and rifampin were investigated. MICs and minimal chlamydicidal concentrations were all within the ranges reported previously. Combinations of azithromycin with either ofloxacin, doxycycline, or rifampin, as well as combinations of three antibiotics (rifampin, azithromycin, and ofloxacin or doxycycline), showed synergistic activity against C. pneumoniae.

Anti-Bacterial Agents↗

PubMed2000

Effect of subinhibitory concentrations of macrolides on expression of flagellin in Pseudomonas aeruginosa and Proteus mirabilis.

In the present study we showed by molecular analysis that the inhibition of motility by macrolides in Proteus mirabilis and Pseudomonas aeruginosa was well correlated with the loss of the expression of flagellin. Erythromycin, clarithromycin, and azithromycin at subinhibitory concentrations (sub-MICs) suppressed the expression of flagellin dose dependently. Azithromycin had the strongest inhibitory effect on the expression of P. aeruginosa flagellin, whereas 16-membered rokitamycin had only a weak inhibitory effect. These results indicate the potential effectiveness of sub-MICs of erythromycin, clarithromycin, and azithromycin for the treatment of patients with P. mirabilis and P. aeruginosa infections.

Anti-Bacterial Agents↗

PubMed2000

A comparative In vitro surveillance study of gemifloxacin activities against 2,632 recent Streptococcus pneumoniae isolates from across Europe, North America, and South America. The Gemifloxacin Surveillance Study Research Group.

From 1997 to 1999, 94 study centers in 15 European, 3 North American, and 2 South American countries contributed 2,632 isolates of Streptococcus pneumoniae to an international antimicrobial susceptibility testing study. Only 62.0% of isolates were susceptible to penicillin, while 22.3% were penicillin intermediate and 15.6% were penicillin resistant. Resistance to trimethoprim-sulfamethoxazole (24.4%), azithromycin (26.0%), and clarithromycin (27.1%) was also highly prevalent. For the penicillin-resistant isolates (n = 411), the MICs at which 90% of isolates are inhibited (MIC(90)s) for gemifloxacin, levofloxacin, ofloxacin, clarithromycin, and azithromycin were 0.03, 1, 2, >16, and >64 microgram/ml, respectively. Similarly, for isolates resistant to both azithromycin and clarithromycin (n = 649), gemifloxacin, levofloxacin, ofloxacin, and penicillin MIC(90)s were 0.03, 1, 2, and 4 microgram/ml, respectively. Overall rates of resistance to trovafloxacin (0.3%), levofloxacin (0.3%), grepafloxacin (0.6%), and ofloxacin (0.7%) were low. For ofloxacin-intermediate and -resistant isolates (n = 142), gemifloxacin had the lowest MIC(90) (0.12 microgram/ml) compared to the MIC(90)s of trovafloxacin (0.5 microgram/ml), grepafloxacin (1 microgram/ml), and levofloxacin (2 microgram/ml). For all S. pneumoniae isolates tested, gemifloxacin MICs were </=0.5 microgram/ml, suggesting that gemifloxacin has the potential to be used as a treatment for pneumococcal infections, including those arising from isolates resistant to beta-lactams and macrolides.

Adolescent↗

PubMed2001

Susceptibilities of Haemophilus influenzae and Moraxella catarrhalis to ABT-773 compared to their susceptibilities to 11 other agents.

The activity of the ketolide ABT-773 against Haemophilus and Moraxella was compared to those of 11 other agents. Against 210 Haemophilus influenzae strains (39.0% beta-lactamase positive), microbroth dilution tests showed that azithromycin and ABT-773 had the lowest MICs (0.5 to 4.0 and 1.0 to 8.0 microg/ml, respectively), followed by clarithromycin and roxithromycin (4.0 to >32.0 microg/ml). Of the beta-lactams, ceftriaxone had the lowest MICs (</=0.004 to 0.016 microg/ml), followed by cefixime and cefpodoxime (0.008 to 0.125 and </=0.125 to 0.25 microg/ml, respectively), amoxicillin-clavulanate (0.125 to 4.0 microg/ml), and cefuroxime (0. 25 to 8.0 microg/ml). Amoxicillin was only active against beta-lactamase-negative strains, and cefprozil had the highest MICs of all oral cephalosporins tested (0.5 to >32.0 microg/ml). Against 50 Moraxella catarrhalis strains, all of the compounds except amoxicillin and cefprozil were active. Time-kill studies against 10 H. influenzae strains showed that ABT-773, at two times the MIC, was bactericidal against 9 of 10 strains, with 99% killing of all strains at the MIC after 24 h; at 12 h, ABT-773 gave 90% killing of all strains at two times the MIC. At 3 and 6 h, killing by ABT-773 was slower, with 99.9% killing of four strains at two times the MIC after 6 h. Similar results were found for azithromycin, with slightly slower killing by erythromycin, clarithromycin, and roxithromycin, especially at earlier times. beta-Lactams were bactericidal against 8 to 10 strains at two times the MIC after 24 h, with slower killing at earlier time periods. Most compounds gave good killing of five M. catarrhalis strains, with beta-lactams killing more rapidly than other drugs. ABT-773 and azithromycin gave the longest postantibiotic effects (PAEs) of the ketolide-macrolide-azalide group tested (4.4 to >8.0 h), followed by clarithromycin, erythromycin, and roxithromycin. beta-Lactam PAEs were similar and shorter than those of the ketolide-macrolide-azalide group for all strains tested.

Anti-Bacterial Agents↗

PubMed2004

In vitro selection and characterization of resistance to macrolides and related antibiotics in Mycoplasma pneumoniae.

Macrolide-resistant mutants of Mycoplasma pneumoniae were selected in vitro from the susceptible reference strain M129, by 23 to 50 serial passages in subinhibitory concentrations of macrolides and related antibiotics, erythromycin A, azithromycin, josamycin, clindamycin, quinupristin, quinupristin-dalfopristin, pristinamycin, and telithromycin. Mutants for which the MICs are increased could be selected with all antibiotics except the streptogramin B quinupristin. Portions of genes encoding 23S rRNA (domains II and V) and ribosomal proteins L4 and L22 of mutants were amplified by PCR, and their nucleotide sequences were compared to those of the susceptible strain M129. No mutation could be detected in domain II of 23S rRNA. Two point mutations in domain V of 23S rRNA, C2611A and A2062G, were selected in the presence of erythromycin A, azithromycin, josamycin, quinupristin-dalfopristin, and telithromycin. Mutants selected in the presence of clindamycin and telithromycin harbored a single amino acid change (H70R or H70L, respectively) in ribosomal protein L4, whereas insertions of one, two, or three adjacent glycines at position 60 (M. pneumoniae numbering) were selected in the presence of both streptogramin combinations. Telithromycin was the sole antibiotic that selected for substitutions (P112R and A114T) and deletions ((111)IPRA(114)) in ribosomal protein L22. Three sequential mutational events in 23S rRNA and in both ribosomal proteins were required to categorize the strain as resistant to the ketolide. Azithromycin and erythromycin A were the only selector antibiotics that remained active (MICs, 0.06 and 1 micro g/ml, respectively) on their mutants selected after 50 passages.

Anti-Bacterial Agents↗