Activity of telithromycin and seven other agents against 1034 pediatric Streptococcus pneumoniae isolates from ten central and eastern European centers

Objective  To test the activity of telithromycin against 1034 Streptococcus pneumoniae isolates from pediatric patients in ten centers from ten central and eastern European countries during 2000–2001, and to compare it with the activities of erythromycin A, azithromycin, clarithromycin, clindamycin, and quinupristin–dalfopristin.
Methods  The minimum inhibitory concentrations (MICs) of telithromycin, erythromycin A, azithromycin, clarithromycin, clindamycin, levofloxacin, quinupristin–dalfopristin and penicillin G were tested by the agar dilution method with incubation in air, and mechanisms of resistance to macrolides and quinolones were investigated.
Results  Strains were isolated from sputum, tracheal aspirates, ear, eye, blood, and cerebrospinal fluid. Among S. pneumoniae strains tested, 36% had raised penicillin G MICs (≥ 0.12 mg/L). Susceptibilities were as follows: telithromycin, quinupristin–dalfopristin and levofloxacin, ≥ 99%; clindamycin, 83%; and erythromycin A, azithromycin and clarithromycin, 78%. Of 230 (22.3%) erythromycin A-resistant S. pneumoniae strains, 176 (79.6%) had erm(B) , 38 (16.1%) had mef(A) , and 10 (4.3%) had mutations in 23S ribosomal RNA or in ribosomal protein L4. The rates of drug-resistant S. pneumoniae are high in all centers except Kaunas, Riga, and Prague.
Conclusion  Telithromycin had low MICs against all strains, irrespective of macrolide, azalide or clindamycin resistance. Ribosomal methylation was the most prevalent resistance mechanism among all resistant strains, except in Sofia, where the prevalence of the efflux mechanism was higher.     

Antimicrobial susceptibility of 840 clinical isolates of Haemophilus influenzae collected in four European countries in 2000–2001

In 2000–2001, 840 clinical isolates of Haemophilus influenzae were collected from laboratories in France, Germany, Italy and Spain (210 isolates/country). β -Lactamase production among the isolates varied considerably by country, ranging from 8.1% in Germany to 34.8% in France. H. influenzae from patients ≤4 years old showed the highest prevalence of β -lactamase production (23.2%), compared with isolates from patients aged 5–17 years (17.8%) and ≥18 years (16.5%). All isolates were susceptible to amoxicillin–clavulanate, ciprofloxacin and levofloxacin; 99.6% and 98.9% of isolates were susceptible to azithromycin and cefuroxime, respectively. Among the macrolides tested, azithromycin (MIC₉₀, 2 mg/L) was eight-fold more potent than clarithromycin (MIC₉₀, 16 mg/L) and roxithromycin (MIC₉₀, 16 mg/L). Despite variations in β -lactamase production between different countries, > 99% of all isolates were susceptible to amoxicillin–clavulanate, ciprofloxacin, levofloxacin, and azithromycin.     

Antimicrobial activity of LB10827, a new orally administered cephalosporin, tested against Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae

A new orally administered cephalosporin, LB10827, was compared to 16 other antimicrobial agents tested against Streptococcus pneumoniae (520 strains), Haemophilus influenzae (302 strains) and Moraxella catarrhalis (188 strains) by reference broth microdilution methods. LB10827 (MIC₉₀, 0.12 mg/L; highest MIC, 0.5 mg/L) was 8–16-fold more potent than cefdinir, cefpodoxime or cefuroxime when tested against S. pneumoniae . All Gram-negative strains were inhibited at ≤ 0.5 mg/L LB10827, which is an activity equal or superior to that of currently available and tested oral β-lactams. LB10827 appears to be a promising agent worthy of continued investigations both in vitro and in vivo.     

The effect of carbon dioxide on susceptibility testing of azithromycin, clarithromycin and roxithromycin against clinical isolates of Streptococcus pneumoniae and Streptococcus pyogenes by broth microdilution and the Etest: Artemis Project—first-phase study

Objective: To evaluate the effect of carbon dioxide on the susceptibility testing, using broth microdilution and the Etest (AB Biodisk, Solna, Sweden), of azithromycin, clarithromycin and roxithromycin against Streptococcus pneumoniae and Streptococcus pyogenes .
Methods: Fresh clinical isolates collected from 36 hospital laboratories in 12 countries were evaluated using the Etest in the presence of carbon dioxide. The isolates were retested under ambient conditions (absence of carbon dioxide) using broth microdilution and/or the Etest.
Results: Carbon dioxide falsely elevated azithromycin, clarithromycin and roxithromycin MIC₉₀S for S. pneumoniae , determined by the Etest, approximately 12-fold. Also, the azithromycin MIC₉₀ for S. pyogenes was increased fourfold; the effect was less marked for clarithromycin and roxithromycin. When isolates were retested in the absence of carbon dioxide, using the Etest or microdilution, susceptibilities to azithroymycin were comparable to those to clarithromycin ( S. pneumoniae , 93.4% versus 91.3%; S. pyogenes , 96.4% versus 95.8%). Both organisms were less susceptible to roxithromycin ( S. pneumoniae , 71.3%; S. pyogenes , 85.7%). An internal standard control, consisting of 50 isolates each of S. pneumoniae, S. pyogenes and Haemophilus influenzae , confirmed that azithromycin susceptibility testing resulted in falsely elevated MICs.
Conclusions: Carbon dioxide falsely elevated azithromycin MICs for S. pneumoniae and S. pyogenes , with an apparent reduction in susceptibility. When the in vitro activity of azithromycin and other macrolides against S. pneumoniae and S. pyogenes is being evaluated, awareness of the pH effect is essential.     

Pharyngeal colonization prevalence rates for Streptococcus pyogenes and Streptococcus pneumoniae in a respiratory chemoprophylaxis intervention study using azithromycin

Objectives   A prospective assessment of the pharyngeal colonization prevalence rates for Streptococcus pyogenes and Streptococcus pneumoniae before and after an azithromycin chemoprophylaxis intervention clinical trial in a cohort of US Marine Corps trainees. In addition, the minimum inhibitory concentrations (MICs) for all streptococcal isolates, for azithromycin, penicillin, erythromycin and cefotaxime are reported.
Methods   Between November 1994 and March 1995, 1108 asymptomatic male US Marine Corps trainees, located in Southern California, were randomly assigned to one of three intervention groups: (1) weekly oral azithromycin, 500 mg ( n  = 362); (2) 1.2 MU benzathine penicillin G, intramuscularly once ( n  = 374); or (3) no chemoprophylaxis ( n  = 372). Subjects provided both a pre- and post-training pharyngeal culture and microbial analysis was conducted to determine the colonization status of each study subject.
Results   The pretraining colonization prevalence was 1.2% for S. pneumoniae and 2.4% for S. pyogenes . There was no statistical difference in pretraining prevalence between the three treatment groups for either organism. Post-training pharyngeal cultures revealed an overall prevalence of 1.1% with no difference between treatment arms. However, the overall post-training prevalence of S. pyogenes colonization increased to 4.8%, with the azithromycin group having significant evidence of protection (0.7%) in comparison with the no-treatment group (8.2%). The Etest method demonstrated no significant difference in the MIC₅₀, MIC₉₀, and MIC ranges between pre- and post-training isolates for any of the tested drugs.
Conclusion The use of azithromycin as a chemoprophylactic agent to reduce the colonization and subsequent infection of streptococcal respiratory disease among healthy adult male military recruits may be beneficial.     

Erythromycin susceptibility of viridans streptococci from the normal throat flora of patients treated with azithromycin or clarithromycin

Objective   To study the emergence of macrolide resistance in throat flora following treatment with clarithromycin or azithromycin.
Methods   Throat samples were collected before and after treatment and plated as a lawn on Columbia blood agar with an erythromycin E test strip. Minimum inhibitory concentrations (MICs) of erythromycin, clarithromycin and azithromycin were determined against isolates of distinct morphology with erythromycin E test MIC results equal to or greater than 2 mg/L. Polymerase chain reaction techniques were used to determine the genetic mechanisms of resistance.
Results   There were 749 resistant isolates of which 474 (63%) were streptococci. Only a quarter of the patients had no resistant streptococci before treatment started. There were increases in the numbers of resistant isolates and in the number of patients carrying a resistant flora during and after treatment. The most common genes identified were mef A/E in isolates with low-level resistance and erm A/M in isolates with high-level resistance.
Conclusions   There is a pool of streptococci carrying genes associated with macrolide resistance in the normal respiratory flora of generally healthy adults. Differences between the patients treated with clarithromycin and those treated with azithromycin were difficult to assess because of the large number of patients in each group with macrolide-resistant streptococci before treatment. Although there were some differences these were not statistically significant.     

Development of interpretive criteria and quality control limits for macrolide and clindamycin susceptibility testing of Streptococcus pneumoniae.

A six-laboratory collaborative study was conducted to develop MIC and zone diameter quality control limits and interpretive criteria for antimicrobial susceptibility testing of Streptococcus pneumoniae with azithromycin, clarithromycin, dirithromycin, and clindamycin. The MICs of all of the agents plus erythromycin for 302 clinical isolates of pneumococci that had been selected with an emphasis on resistant strains were determined by use of the National Committee for Clinical Laboratory Standards (NCCLS)-recommended broth microdilution procedure. The zone diameters of the isolates were also determined for the same agents except erythromycin by the NCCLS disk diffusion test procedure. Repeated testing of S. pneumoniae ATCC 49619 with different sources and lots of media and disks allowed development of MIC and zone diameter quality control ranges for these agents. Interpretive criteria for the MIC of azithromycin were established and were as follows: susceptible, < or = 0.5 microgram/ml; intermediate, 1 microgram/ml; and resistant, > or = 2 micrograms/ml. The interpretive criteria advocated for the MICs of clarithromycin and clindamycin were as follows: susceptible, < or = 0.25 microgram/ml; intermediate, 0.5 microgram/ml; and resistant, > or = 1 microgram/ml. Comparison of MICs and disk diffusion zone diameters led to the development of interpretive criteria for the zone diameters for azithromycin, clarithromycin, and clindamycin that correlated well with these MIC breakpoints. Testing of this organism collection also led to the reestablishment of the erythromycin MIC breakpoints as being identical to those of clarithromycin, which resulted in equivalent cross-susceptibility and cross-resistance for the three macrolides that are currently marketed in the United States. Thus, the susceptibility of pneumococci to azithromycin and clarithromycin can be predicted accurately by testing only erythromycin in clinical laboratories. This recommendation, as well as the interpretive and quality control criteria that are described, have been accepted by NCCLS and are included in the latest NCCLS susceptibility testing guidelines.     

Activity of the new quinolone WCK 771 against pneumococci

The activity of WCK 771, a new experimental quinolone being developed to overcome quinolone resistance in staphylococci, against quinolone-susceptible and -resistant pneumococci was determined. Comparative activities of ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, clinafloxacin, vancomycin, linezolid, amoxycillin, cefuroxime, azithromycin and clarithromycin were determined with MIC and time-kill experiments. Animal experiments were also performed to test the in-vivo anti-pneumococcal activity of WCK 771 compared to levofloxacin. WCK 771 MIC50/90 values for 300 quinolone-susceptible Streptococcus pneumoniae isolates (108 penicillin-susceptible, 92 penicillin-intermediate and 100 penicillin-resistant) were 0.5/0.5 mg/L; the MICs of beta-lactams and macrolides rose with those of penicillin G, and all isolates were susceptible to vancomycin and linezolid. WCK 771 MIC50/90 values for 25 quinolone-resistant pneumococcal isolates were 4/8 mg/L, compared to 0.5/1 mg/L for clinafloxacin, 2/4 mg/L for gatifloxacin and moxifloxacin, 8/16 mg/L for levofloxacin, and 16/>32 mg/L for ciprofloxacin. Time-kill studies showed that WCK 771 was bactericidal against pneumococci after 24 h at 4 x MIC, as were the other quinolones tested. Animal model studies showed that WCK 771 had efficacy comparable to that of levofloxacin, by both the oral and subcutaneous routes, for systemic infection caused by three quinolone-susceptible isolates of pneumococci. Overall, WCK 771 was potent both in vivo and in vitro against quinolone-susceptible, but not quinolone-resistant, S. pneumoniae, regardless of penicillin susceptibility.     

In vitro activity of tigecycline and occurrence of tetracycline resistance determinants in isolates from patients enrolled in phase 3 clinical trials for community-acquired pneumonia

The in vitro activity of tigecycline was evaluated against baseline pathogens isolated from patients enrolled in phase 3 clinical trials for community-acquired pneumonia conducted in 29 countries worldwide. Tigecycline was active against the most prevalent pathogens, including Streptococcus pneumoniae (MIC₉₀ 0.06 mg/L), Staphylococcus aureus (MIC₉₀ 0.25 mg/L), Haemophilus influenzae (MIC₉₀ 0.5 mg/L) and Klebsiella pneumoniae (MIC₉₀ 1 mg/L). Twelve isolates of S. pneumoniae expressing tet (M) and two isolates of K. pneumoniae producing extended-spectrum β-lactamases isolated during the study were susceptible to tigecycline. The excellent in vitro activity of tigecycline against these clinical isolates confirmed its potential utility against pathogens associated with community-acquired pneumonia.     

Activity of telithromycin against 26 quinolone-resistant pneumococci with known quinolone-resistance mechanisms

NCCLS agar dilution was used to test activity of telithromycin compared to clarithromycin, penicillin G, ciprofloxacin, levofloxacin, sparfloxacin and moxifloxacin against 26 pneumococci with defined quinolone resistance (type II topoisomerase and efflux) mechanisms. Thirteen strains were penicillin susceptible, six intermediate and seven resistant. Clarithromycin resistance ( mef and/or erm ) was seen in eight strains. Ciprofloxacin MICs (mg/L) were 8–64 compared to 1–32 (levofloxacin), 0.5 ≥ 32 (sparfloxacin) and 0.125–4 (moxifloxacin). Telithromycin MIC₅₀ and MIC₉₀ values (mg/L) were 0.016 and 0.25, with only one strain having an MIC of 2 mg/L.     

Antimicrobial susceptibility of Streptococcus pneumoniae in Latin America: results from five years of the SENTRY Antimicrobial Surveillance Program.

A total of 1561 pneumococcal isolates were collected in 1997-2001, mainly from patients with community-acquired respiratory tract infections, and susceptibilities were tested by reference broth microdilution against 29 antimicrobial agents. In general, 69.3% of strains were considered susceptible (MIC < or = 0.06 mg/L) to penicillin. Resistance to penicillin (MIC > or = 2 mg/L) and cefotaxime (MIC > or = 4 mg/L) was found in 11.9% and 0.4% of isolates, respectively. The fluoroquinolones gatifloxacin (MIC90, 0.5 mg/L) and levofloxacin (MIC90, 1 mg/L) were active against > 99% of the isolates tested. Among the other non-beta-lactam drugs tested, the rank order of susceptibility was chloramphenicol (95.6%) > clindamycin (94.5%) > azithromycin (88.5%) > clarithromycin (87.5%) >tetracycline (79.5%) > trimethoprim + sulphamethoxazole (60.5%). The penicillin-non-susceptible isolates presented higher rates of resistance to other antimicrobial agents. The rank order of penicillin resistance rates among the seven participating countries was Mexico (25.0%) > Uruguay (19.2%) > Chile (18.3%) > Colombia = Argentina (9.9%) > Brazil (3.9%) > Venezuela (2.8%). The regional rate of penicillin resistance did not vary significantly over the years studied (p 0.339). Screening for the ermB and mefA genes by multiplex rapid cycle PCR on 23 erythromycin-resistant isolates collected during the year 2001 showed that 43.5% and 56.5%, respectively, were positive for ermB and mefA. Overall, the results indicated that antimicrobial susceptibilities of Streptococcus pneumoniae vary significantly among Latin American countries. Regional and local surveillance programmes are necessary to guide empirical therapy of pneumococcal infection in Latin American countries.     

Macrolide resistance in Streptococcus pneumoniae isolated from patients with community-acquired lower respiratory tract infections in Portugal: results of a 3-year (1999-2001) multicenter surveillance study

A nationwide multicenter study (including 31 laboratories) of the antimicrobial susceptibility of 1210 Streptococcus pneumoniae isolates from patients with community-acquired lower respiratory tract infections (LRTI) was carried out over 3 years (1999-2001) in Portugal. Testing of all isolates was undertaken in a central laboratory. Overall macrolide resistance was 13.1%. Decreased susceptibility to penicillin was 24.5% (15.5% low-level and 9.0% high-level resistance). Taken into consideration, the resistance rates reported in a previous surveillance study of 1989-1993, a six-fold increase of erythromycin resistance in the last decade was documented. Resistance to erythromycin, clarithromycin, and azithromycin was higher in pediatric patients than in adults. The overwhelming majority (82.3%) of macrolide-resistant isolates were multidrug resistant, although 44.9% were fully susceptible to penicillin. Most macrolide-resistant isolates (80.4%) showed the MLSB phenotype (76.6% MLSB-constitutive resistance, and 3.8% MLSB-inducible resistance) and were also resistant to clindamycin, tetracycline, and co-trimoxazole. The M phenotype was seen in 19.6% isolates and these had MIC90 values of 8 mg/L for erythromycin and clarithromycin, and of 12 mg/L for azithromycin. The clinical significance of macrolide resistance in the management of LRTI is discussed. Because of the specific situation concerning macrolide resistance described in S. pneumoniae, careful use of macrolide antibiotics in therapy and cautious monitoring of macrolide resistance should be continued in Portugal.     

Comparison of in vitro activities of tigecycline with other antimicrobial agents against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in Taiwan

We compared the in vitro activities of tigecycline to those of other agents against 300 nonduplicate isolates of Streptococcus pneumoniae (194 isolates), Haemophilus influenzae (60 isolates), and Moraxella catarrhalis (46 isolates) recovered from patients treated in three major hospitals in Taiwan from August through December, 2003. All of these isolates were inhibited at 0.5 mg/L of tigecycline. For S. pneumoniae isolates, 72% were not susceptible to penicillin (69% intermediate and 3% resistant) and 96% were not susceptible to azithromycin. Among the 178 isolates resistant to azithromycin, 53 isolates (30%) had the M phenotype and 70% had the cMLSB phenotype. The rate of nonsusceptibility to ertapenem, telithromycin, moxifloxacin, and quinupristindalfopristin in S. pneumoniae was 3%, 2%, 1%, and 57%, respectively. For H. influenzae, 36 (60%) were not susceptible to ampicillin, among which 31 possessed beta-lactamase. A high rate (8.3%) of H. influenzae isolates with beta-lactamase-negative and ampicillin-resistant phenotype was found. All H. influenzae isolates were susceptible to azithromycin, but 40% of them were not susceptible to clarithromycin. Ninety-eight percent (44 isolates) of M. catarrhalis possessed beta-lactamase. All three fluoroquinolones tested were highly active (MIC90 < or =0.12 mg/L) against H. influenzae and M. catarrhalis.     

In vitro activity of telithromycin (HMR 3647) against Greek Streptococcus pyogenes and Streptococcus pneumoniae clinical isolates with different macrolide susceptibilities

The susceptibilities to macrolides and telithromycin of 161 Streptococcus pyogenes and 145 Streptococcus pyogenes strains, consecutively isolated from five Greek hospitals, were determined by Etest. Moreover, mechanisms of resistance to macrolides were phenotypically and genetically determined by double disk induction test and PCR, respectively. Of the S. pneumoniae and S. pyogenes isolates, 42.8% and 30.8%, respectively, were found to be resistant to erythromycin. Of the erythromycin-resistant S. pneumoniae and S. pyogenes isolates, 57.5% and 59.5%, respectively, displayed the M phenotype and harbored the mefA/E gene. Telithromycin was found to be more active than both erythromycin and clarithromycin against both species, with considerably lower MIC₅₀ and MIC₉₀ values.     

In vitro activity of evernimicin and selected antibiotics against methicillin-resistant staphylococci: a 24-country study

Objective   To collect and analyze data on susceptibility of methicillin-resistant staphylococci to evernimicin and other antimicrobial agents.
Methods   Recent clinical isolates of methicillin-resistant staphylococci from 33 laboratories in North America, Europe and South Africa were investigated.
Results   Of the antimicrobial agents tested, evernimicin had the lowest MIC₉₀s for methicillin-resistant Staphylococcus aureus and methicillin-resistant coagulase-negative staphylococci (0.75 and 1.0 mg/L, respectively). Resistance to ciprofloxacin and erythromycin was widespread, with higher levels of resistance in North America than in other regions.
Conclusions   Susceptibility surveys help to determine the antimicrobial activity of new agents. Ciprofloxacin- and erythromycin-resistant staphylococci were prevalent throughout all regions.     

In vitro activities of new quinolones against Brucella melitensis isolated in a tertiary-care hospital in Turkey

We have evaluated the in vitro activities of seven fluoroquinolones against 69 strains of Brucella melitensis . According to their minimum inhibitory concentration for 90% growth (MIC₉₀) values, the most active agent was found to be sparfloxacin (MIC₉₀ 0.12 mg/L) followed by levofloxacin, ciprofloxacin, ofloxacin (MIC₉₀ 0.50 mg/L) and grepafloxacin (MIC₉₀ 1 mg/L), gemifloxacin (MIC₉₀ 2 mg/L) and gatifloxacin (MIC₉₀ 4 mg/L).     

In vivo efficacy of cefotaxime and amoxicillin against penicillin-susceptible, penicillin-resistant and penicillin-cephalosporin-resistant strains of Streptococcus pneumoniae in a mouse pneumonia model

Objective: To compare cefotaxime (CTX) to amoxicillin (AMO) (usually considered the definitive therapy for penicillinsusceptible Streptococcus pneumoniae infections) in an immunocompromised mouse pneumonia model.
Methods: Three S. pneumoniae clinical isolates were used: two serotype 19 strains, a penicillin-susceptible (P^s) strain (penicillin MIC = 0.03 μ/mL) and a highly penicillin-resistant (P^r) strain (penicillin MIC = 4 μ/mL), and one serotype 23F strain, a penicillin-cephalosporin-resistant (CFTR) strain (CTX MIC = 4 μ/mL).
Results: CTX activity in this mouse model of pneumonia induced by the highly penicillin-resistant strain of S. pneumoniae was lower than expected from its low MIC against this organism. Furthermore, AMO had greater efficacy than CTX against a CFTR S. pneumoniae strain.
Conclusion: Our data suggest that there is no major difference in the in vivo efficacy of the two agents, cefotaxime and amoxicillin, against penicillin-resistant and penicillin-cephalosporin-resistant S. pneumoniae.     

Effect of pH variation on the susceptibility ofHelicobacter pylori to three macrolide antimicrobial agents and temafloxacin

The in vitro susceptibility of 27 clinical isolates ofHelicobacter pylori to erythromycin, clarithromycin, azithromycin and temafloxacin under various pH conditions was evaluated. Clarithromycin (MIC90 0.03 µg/ml) was found to be significantly more active than either erythromycin (MIC90 0.125 µg/ml) or azithromycin (MIC90 0.25 µg/ml) at a neutral pH. Lowering the pH to 5.75 resulted in a loss in efficacy from 8- to 32-fold for all three macrolides studied. The MIC90 of clarithromycin (0.5 µg/ml) remained lower than those of azithromycin (2 µg/ml) and erythromycin (4 µg/ml). No synergism or antagonism was observed with combinations of clarithromycin and temafloxacin at either the neutral or lower pH values.     

Choice of antimicrobial drug for infections caused by Chlamydia trachomatis and Chlamydophila pneumoniae

Chlamydia (C.) trachomatis is the most common bacterial cause of sexually transmitted disease in the world. A well documented feature of chlamydial infection is its high rate of recurrence among sexually active populations. However, it is difficult to distinguish whether the high rate of recurrent disease is due to reinfection or to persistent infection with the same organism. Of particular concern in this era of increasing antibiotic resistance is whether persistent infection is the consequence of increasing resistance to standard antimicrobial therapy. Azithromycin and doxycycline are considered by the Centers for Disease Control and Prevention (CDC) as first line drugs for the treatment of chlamydial infections; erythromycin, ofloxacin and levofloxacin are recommended as alternative-regimen. Although C. trachomatis has been historically sensitive to these antibiotics, in vitro resistance is being increasingly reported. However, although in vitro antimicrobial resistance has been described, the clinical significance of these findings is unknown. C. pneumoniae is associated with community-acquired pneumonias, acute exacerbations of chronic bronchitis, otitis media, sinusitis and reactive airway disease. Persistent nasopharyngeal infection with C. pneumoniae has been documented in adults following acute respiratory infection. Chronic infection with C. pneumoniae has also been implicated in the pathogenesis of atherosclerosis, although this is still very controversial. Azithromycin, clarithromycin and quinolones are frequently used for the treatment of C. pneumoniae respiratory infections. Microbiologic failure has been described in C. pneumoniae infections, even after prolonged courses of azithromycin, erythromycin and doxycycline.     

Antimicrobial activity of ten macrolide,linsosamine and streptogramin drugs tested againstLegionella species

RP59500, a semisynthetic pristinamycin combination, and 14 other antimicrobial agents were tested against 108Legionella strains. Of the ten macrolide, lincosamine and streptogramin agents tested, the new streptogramin RP59500 ranked seventh in order of activity againstLegionella pneumophila on the basis of MIC90 results as follows: clarithromycin = 14-OH clarithromycin (MIC90 0.12 mg/l) > roxithromycin > erythromycin = tylosin = virginiamycin > RP59500 (MIC90 1 mg/l) = azithromycin > dirithromycin > clindamycin (MIC90 8 mg/l). Of all 14 drugs tested in this study, rifampicin was the most potent with an MIC90 of 0.008 mg/l. In this retrospective study ofLegionella strains (1981–1990 isolates), we observed no trend toward resistance to the agents investigated.