In vitro susceptibilities of mycoplasmas and ureaplasmas to new macrolides and aryl-fluoroquinolones.

In vitro activities of the new macrolides clarithromycin, previously designated A-56268 (TE-031), and A-63075 and of the aryl-fluoroquinolones difloxacin (A-56619) and temafloxacin (A-62254) against 14 strains of Mycoplasma pneumoniae, 20 strains of Mycoplasma hominis, and 28 strains of Ureaplasma urealyticum were compared with that of erythromycin. All three macrolides inhibited growth of M. pneumoniae at less than 0.125 micrograms/ml. No macrolide was active against M. hominis. For five strains of U. urealyticum, MICs were greater than 256 micrograms/ml for all 3 macrolides. Excluding these, no other strain of U. urealyticum had an initial MIC of clarithromycin of greater than 1 microgram/ml, while five had initial MICs of erythromycin which were greater than 4 micrograms/ml. A-63075 was the least active of the three macrolides against ureaplasmas. Temafloxacin and difloxacin had similar activities against all three species, initially inhibiting 90% of M. pneumoniae strains at 2 and 8 micrograms/ml, 90% of M. hominis strains at 2 and 4 micrograms/ml, and 90% of U. urealyticum strains at 4 and 8 micrograms/ml, respectively. Additional pharmacokinetic and clinical trials with the new macrolides and quinolones with mycoplasmal or ureaplasmal infections are indicated.     

Susceptibilities of Mycoplasma hominis, Mycoplasma pneumoniae, and Ureaplasma urealyticum to new glycylcyclines in comparison with those to older tetracyclines.

The glycylcyclines are new tetracycline derivatives that include the N,N-dimethylglycylamido derivative of minocycline (DMG-MINO) and the N,N-dimethylglycylamido derivative of 6-demethyl-6-deoxytetracycline (DMG-DMDOT). The susceptibilities of Mycoplasma pneumoniae, Mycoplasma hominis, and Ureaplasma urealyticum to DMG-MINO, DMG-DMDOT, tetracycline, doxycycline, and minocycline were determined by the agar dilution method. The glycylcyclines with MICs at which 50% of the isolates are inhibited of 0.25 to 0.5 micrograms/ml for M. pneumoniae were two- to fourfold more active than tetracycline and had the same activity as minocycline and doxycycline. Tetracycline-susceptible M. hominis strains were four- to eightfold more susceptible to the glycylcyclines (0.12 to 0.25 micrograms/ml) than to tetracycline. Strains of M. hominis known to be resistant to tetracycline, doxycycline, and minocycline because of the tet(M) determinant were as susceptible to the glycylcyclines as the tetracycline-susceptible strains. For tetracycline-susceptible U. urealyticum strains, the glycylcyclines showed the same activity as tetracycline (MICs at which 50% of the isolates are inhibited of 1 to 2 micrograms/ml). Tetracycline-resistant strains of U. urealyticum were resistant to doxycycline and minocycline and showed variable susceptibility to the glycylcyclines (range, 0.5 to 32 micrograms/ml). In view of the increasing resistance of M. hominis and U. urealyticum strains to tetracyclines, the glycylcyclines have promise, pending assessment of their pharmacokinetic and safety profiles.     

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.     

In vitro activity of telithromycin (HMR3647), a new ketolide, against clinical isolates of Mycoplasma pneumoniae in Japan

The in vitro activity of telithromycin (HMR3647), a new ketolide, against Mycoplasma pneumoniae was determined by the broth microdilution test using 41 clinical isolates obtained in Japan, as compared with those of five macrolides (erythromycin, clarithromycin, roxithromycin, azithromycin, and josamycin), minocycline, and levofloxacin. Telithromycin was less potent than azithromycin, but it was more active than four other macrolides, minocycline, and levofloxacin; its MICs at which 50 and 90% of the isolates tested were inhibited were both 0.00097 microg/ml, justifying clinical studies to determine its efficacy for treatment of M. pneumoniae.     

Susceptibilities of Mycoplasma pneumoniae, Mycoplasma hominis, and Ureaplasma urealyticum to a new quinolone, trovafloxacin (CP-99,219).

The susceptibilities of mycoplasmas to a new quinolone, trovafloxacin (CP-99,219), were compared with those to sparfloxacin and ofloxacin. Mycoplasma pneumoniae was as susceptible to trovafloxacin (MIC = 0.25 microgram/ml) as to sparfloxacin and fourfold less susceptible to ofloxacin. Mycoplasma hominis was highly susceptible to trovafloxacin (MIC = 0.06 microgram/ml) and sparfloxacin (MIC = 0.03 microgram/ml) and less susceptible to ofloxacin (MIC = 0.5 microgram/ml). Ureaplasma urealyticum was most susceptible to trovafloxacin, with susceptibilities ranging from 0.06 to 0.5 microgram/ml compared with 0.25 to 1.0 microgram of sparfloxacin per ml and 1 to 4 micrograms of ofloxacin per ml.     

Emergence of a 23S rRNA mutation in Mycoplasma hominis associated with a loss of the intrinsic resistance to erythromycin and azithromycin

OBJECTIVES: Mycoplasma hominis is intrinsically resistant to 14- and 15-membered macrolides and to the ketolide telithromycin but is susceptible to josamycin, a 16-membered macrolide, and lincosamides. The aim of our study was to investigate the in vitro development of macrolide resistance in M. hominis and to study the impact of ribosomal mutations on MICs of various macrolides and related antibiotics. METHODS: Selection of macrolide-resistant mutants was performed by serial passages of M. hominis PG21 in broth medium containing subinhibitory concentrations of clindamycin, pristinamycin, quinupristin/dalfopristin and telithromycin. Stepwise selection of josamycin-resistant mutants was performed onto agar medium containing increasing inhibitory concentrations of josamycin. Resistant mutants were characterized by PCR amplification and DNA sequencing of 23S rRNA, L4 and L22 ribosomal protein genes. RESULTS: Various mutations in domain II or V of 23S rRNA were selected in the presence of each selector antibiotic and were associated with several resistance phenotypes. Josamycin was the sole antibiotic that selected for single amino acid changes in ribosomal proteins L4 and L22. Unexpectedly, the C2611U transition selected in the presence of clindamycin and the quinupristin/dalfopristin combination was associated with decreased MICs of erythromycin, azithromycin and telithromycin, leading to a loss of the intrinsic resistance of M. hominis to erythromycin and azithromycin. CONCLUSIONS: Ribosomal mutations were associated with resistance to macrolides and related antibiotics in M. hominis. Some mutants showed a loss of the intrinsic resistance to erythromycin and azithromycin.     

Susceptibilities of Mycoplasma hominis, Mycoplasma pneumoniae, and Ureaplasma urealyticum to a new quinolone, OPC 17116.

The susceptibilities of human mycoplasmas to OPC 17116 (Otsuka America Pharmaceutical, Inc., Rockville, Md.) and temafloxacin (Abbott Laboratories, Chicago, Ill.) were determined by the agar dilution method and were compared with those to sparfloxacin and ofloxacin. The MICs of OPC 17116 for 90% of Mycoplasma pneumoniae (0.25 microgram/ml) and Mycoplasma hominis (0.125 micrograms/ml) isolates tested were closely similar to those of sparfloxacin and were four- to eightfold greater than those of ofloxacin. Temafloxacin was two- to fourfold more active than ofloxacin. Ureaplasma urealyticum was less susceptible; the MICs of OPC 17116 and temafloxacin for 90% of isolates tested were 2 and 4.0 micrograms/ml, respectively.     

Antimicrobial resistance in respiratory tract Streptococcus pneumoniae isolates: results of the Canadian Respiratory Organism Susceptibility Study, 1997 to 2002

A total of 6,991 unique patient isolates of Streptococcus pneumoniae were collected from October 1997 to June 2002 from 25 medical centers in 9 of the 10 Canadian provinces. Among these isolates, 20.2% were penicillin nonsusceptible, with 14.6% being penicillin intermediate (MIC, 0.12 to 1 microg/ml) and 5.6% being penicillin resistant (MIC, > or =2 microg/ml). The proportion of high-level penicillin-resistant S. pneumoniae isolates increased from 2.4 to 13.8% over the last 3 years of the study, and the proportion of multidrug-resistant S. pneumoniae isolates increased from 2.7 to 8.8% over the 5-year period. Resistant rates (intermediate and resistant) among non-beta-lactam agents were as follows: macrolides, 9.6 to 9.9%; clindamycin, 3.8%; doxycycline, 5.5%; chloramphenicol, 3.9%; and trimethoprim-sulfamethoxazole, 19.0%. Rates of resistance to non-beta-lactam agents were higher among penicillin-resistant strains than among penicillin-susceptible strains. No resistance to vancomycin or linezolid was observed; however, 0.1% intermediate resistance to quinupristin-dalfopristin was observed. The rate of macrolide resistance (intermediate and resistant) increased from 7.9 to 11.1% over the 5 years. For the fluoroquinolones, the order of activity based on the MICs at which 50% of isolates are inhibited (MIC(50)s) and the MIC(90)s was gemifloxacin > clinafloxacin > trovafloxacin > moxifloxacin > grepafloxacin > gatifloxacin > levofloxacin > ciprofloxacin. The investigational compounds ABT-773 (MIC(90), 0.008 microg/ml), ABT-492 (MIC(90), 0.015 microg/ml), GAR-936 (tigecycline; MIC(90), 0.06 microg/ml), and BMS284756 (garenoxacin; MIC(90), 0.06 micro g/ml) displayed excellent activities. Despite decreases in the rates of antibiotic consumption in Canada over the 5-year period, the rates of both high-level penicillin-resistant and multidrug-resistant S. pneumoniae isolates are increasing in Canada.     

Activity of DX-619 compared to other agents against viridans group streptococci, Streptococcus bovis, and Cardiobacterium hominis

Against 198 viridans group streptococci, 25 Streptococcus bovis strains, and 5 Cardiobacterium hominis strains, MICs of DX-619, a des-F(6)-quinolone, were between 0.004 and 0.25 microg/ml. These MICs were lower than those of other quinolones (< or = 0.008 to > 32 microg/ml). Beta-lactam MICs were between < or = 0.008 and 16 microg/ml. Azithromycin resistance was found in most species, while most were telithromycin susceptible. Glycopeptides and linezolid were active against viridans group strains but inactive against C. hominis.     

In vitro susceptibilities to and bactericidal activities of garenoxacin (BMS-284756) and other antimicrobial agents against human mycoplasmas and ureaplasmas

The in vitro susceptibilities to garenoxacin (BMS-284756), an investigational des-fluoroquinolone, and eight other agents were determined for 63 Mycoplasma pneumoniae, 45 Mycoplasma hominis, 15 Mycoplasma fermentans, and 68 Ureaplasma sp. isolates. Garenoxacin was the most active quinolone, inhibiting all isolates at 相似文献   

Antimicrobial activity and spectrum of the new glycylcycline, GAR-936 tested against 1,203 recent clinical bacterial isolates

The in vitro activity of GAR-936, a new semisynthetic glycylcycline, was evaluated in comparison with two tetracyclines and several other antimicrobial agents. A total of 1,203 recent clinical isolates were tested by reference broth or agar dilution methods. Among the members of the family Enterobacteriaceae, GAR-936 was generally two- to four-fold more active than minocycline, and two- to 16-fold more active than tetracycline. All enteric bacilli MIC90 results were < or = 4 microg/mL; the exception being Proteus mirabilis and indole-positive Proteae (> or = 8 microg/mL). GAR-936 demonstrated excellent activity against all gram-positive cocci with 90% of the penicillin-resistant Streptococcus pneumoniae isolates inhibited at 0.03 microg/ml, while the same isolates had a MIC90 of 8 and > 8 microg/mL for minocycline and tetracycline, respectively. All Enterococcus spp., including vancomycin-resistant isolates, were inhibited at 0.25 microg/mL of GAR-936 (MIC90, 0.12 or 0.25 microg/mL). Although GAR-936 (MIC50, 0.25 microg/mL) was two-fold less active than minocycline (MIC50, 0.12 microg/mL) against oxacillin-resistant Staphylococcus aureus, all isolates were inhibited at < or = 0.25 microg/mL. GAR-936 demonstrated good activity against nonfermentative bacteria such as Acinetobacter spp. (MIC90, 2 microg/ml) and Stenotrophomonas maltophilia (MIC90, 4 microg/mL), but the compound exhibited only modest activity against Pseudomonas aeruginosa (MIC50, 8 microg/mL). Haemophilus influenzae (MIC90, 1-2 microg/mL), Moraxella catarrhalis (MIC90, 0.12 microg/mL), and various Neisseria spp. (MIC90, 0.12-0.5 microg/mL) were susceptible to GAR-936. These results indicate that GAR-936 has potent in vitro activity against a wide range of clinically important pathogenic bacteria, and that several gram-positive and -negative isolates resistant to older tetracyclines and other drug classes remain susceptible to GAR-936, the newest glycylcycline candidate for clinical use.     

Susceptibilities of genital mycoplasmas to the newer quinolones as determined by the agar dilution method.

The increasing resistance of genital mycoplasmas to tetracycline poses a problem because tetracycline is one of the few antimicrobial agents active against Mycoplasma hominis, Ureaplasma urealyticum, chlamydiae, gonococci, and other agents of genitourinary-tract disease. Since the quinolones are a promising group of antimicrobial agents, the susceptibilities of M. hominis and U. urealyticum to the newer 6-fluoroquinolones were determined by the agar dilution method. Ciprofloxacin, difloxacin, and ofloxacin had good activity against M. hominis, with the MIC for 50% of isolates tested (MIC50) being 1 microgram/ml. Fleroxacin, lomefloxacin, pefloxacin, and rosoxacin had MIC50s of 2 micrograms/ml. Enoxacin, norfloxacin, and amifloxacin had MIC50s of 8 to 16 micrograms/ml, and cinoxacin and nalidixic acid were inactive (MIC50, greater than or equal to 256 micrograms/ml). Overall, the activities of 6-fluoroquinolones for ureaplasmas were similar to those for M. hominis, with MICs being the same or twofold greater. The most active 6-fluoroquinolones against ureaplasmas were difloxacin, ofloxacin, and pefloxacin, with MIC50s of 1 to 2 micrograms/ml. Ciprofloxacin was unusual in that the MIC50 for M. hominis was 1 microgram/ml, whereas the MIC50 for ureaplasmas was 8 micrograms/ml. Since the MIC50s for the most active quinolones approximate achievable concentrations in blood and urine, quinolones have promise in treating mycoplasmal infections.     

In vitro activities of ABT-773 and other antimicrobials against human mycoplasmas

The in vitro susceptibilities of 103 Mycoplasma pneumoniae isolates, 14 Mycoplasma hominis isolates, 12 Mycoplasma fermentans isolates, and 24 Ureaplasma species to ABT-773, an investigational ketolide, and seven other agents were determined. For M. pneumoniae, the ABT-773 MIC at which 90% of isolates are inhibited (MIC(90); or=16-fold lower than those of all three fluoroquinolones. Minimal bactericidal concentrations determined for a subgroup of organisms were 相似文献   

男性泌尿生殖道支原体感染698例的调查及耐药性分析

目的了解男性泌尿生殖道支原体感染的分布状况,对抗菌药物的耐药性进行分析,指导临床合理使用抗菌药物。方法用珠海益民生物工程制品公司生产的支原体试剂盒进行支原体培养鉴定、计数及药敏试验。结果2 287份男性泌尿生殖道标本中共分离出698株支原体,阳性率为30．5%。其中解脲脲原体563株,占80．7%,人型支原体26株,占3．7%,解脲脲原体合并人型支原体感染109株,占15．6%。分离出的解脲脲原体对交沙霉素最敏感,人型支原体对多西环素、米诺环素的敏感率为100%,对红霉素、罗红霉素、克拉霉素耐药率为100%。结论治疗支原体感染的首选药为交沙霉素、多西环素、米诺环素。进行支原体培养、鉴定和药敏试验,可以根据药敏结果指导临床合理使用抗菌药物。     

In vitro activity of GAR-936 against vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae

We report the activity of the new glycylcycline antimicrobial agent GAR-936 against 37 clinical isolates of vancomycin-resistant enterococci (including organisms carrying the vanA, vanB, vanC-1, and vanC-2/3 genes), 26 clinical isolates of methicillin-resistant S. aureus and 30 clinical isolates of high-level penicillin-resistant S. pneumoniae. All isolates of vancomycin-resistant enterococci, methicillin-resistant S. aureus, and penicillin-resistant S. pneumoniae were inhibited by < or = 1, < or = 2, or < or = 0.25 microg/ml of GAR-936, respectively. Time kill experiments using vancomycin-resistant enterococci did not demonstrate synergy or antagonism between 2 microg/ml of GAR-936 and 0.25 microg/ml of quinupristin/dalfopristin.     

In vitro antimycoplasmal activities of rufloxacin and its metabolite MF 922.

The in vitro activities of rufloxacin and its metabolite, MF 922, were compared with those of ofloxacin, ciprofloxacin, erythromycin, and minocycline against Mycoplasma pneumoniae, Mycoplasma hominis, Mycoplasma fermentans, and Ureaplasma urealyticum. Rufloxacin, MF 922, and ciprofloxacin shared similar activities against all mycoplasmas tested. (MICs for 90% of isolates tested [MIC90s], 0.5 to 4 micrograms/ml. Ofloxacin had the lowest MIC90s for U. urealyticum, M. fermentans, and M. hominis (MIC90s, 0.25 to 1 micrograms/ml) and erythromycin had the lowest MIC90 for M. pneumoniae (MIC90, 0.004 micrograms/ml).     

Susceptibilities of Mycoplasma hominis and Ureaplasma urealyticum to two new quinolones, sparfloxacin and WIN 57273.

Mycoplasma hominis was highly susceptible to two new quinolones, with MICs for 90% of isolates tested of 0.004 micrograms/ml for WIN 57273 and 0.063 micrograms/ml for sparfloxacin, which were activities much greater than the 1 microgram/ml found for ofloxacin and tetracycline. Although Ureaplasma urealyticum was less susceptible, the MICs for 90% of isolates tested of 0.25 micrograms/ml for WIN 57273 and 0.5 micrograms/ml for sparfloxacin were four- to eightfold greater than those found for ofloxacin (2 micrograms/ml) and tetracycline (2 micrograms/ml). The finding that U. urealyticum and M. hominis are more susceptible to WIN 57273 and sparfloxacin than they are to other quinolones suggests that these quinolones may be therapeutically useful.     

In vitro susceptibilities of Mycoplasma pneumoniae, Mycoplasma hominis, and Ureaplasma urealyticum to sparfloxacin and PD 127391.

The in vitro activities of two investigational quinolones, sparfloxacin (previously designated AT 4140) and PD 127391, were determined for 30 strains each of Mycoplasma pneumoniae, Mycoplasma hominis, and Ureaplasma urealyticum and compared with those of ciprofloxacin, tetracycline, clindamycin, and erythromycin. Erythromycin was the most active compound against M. pneumoniae (maximum MIC, less than 0.008 microgram/ml). PD 127391 (MICs, less than 0.008 to 0.031 microgram/ml), sparfloxacin (MICs, less than 0.008 to 0.25 microgram/ml), clindamycin (MICs, less than 0.008 to 0.5 microgram/ml), and tetracycline (MICs, 0.063 to 0.25 microgram/ml) were superior to ciprofloxacin (MICs, 0.5 to 2 microgram/ml). Sparfloxacin and PD 127391 were active against M. hominis (MICs, less than 0.008 to 0.031 microgram/ml for each) at concentrations comparable to those of clindamycin (MICs, less than 0.008 to 0.063 microgram/ml) and at concentrations lower than those of ciprofloxacin (MICs, 0.125 to 0.5 microgram/ml). As expected, M. hominis was resistant to erythromycin (MICs, 32 to greater than or equal to 256 micrograms/ml). For U. urealyticum, PD 127391 (MICs, 0.031 to 0.5 microgram/ml) and sparfloxacin (MICs, 0.063 to 1 microgram/ml) were superior to erythromycin (MICs, 0.25 to 4 micrograms/ml), ciprofloxacin (MICs, 0.5 to 8 micrograms/ml), and clindamycin (MICs, 0.25 to 64 micrograms/ml. Both new quinolones were equally active against tetracycline-susceptible as well as resistant strains of M. hominis and U. urealyticum. The possible influence of medium components and/or pH on MICs was evaluated by testing a Staphylococcus aureus reference strain with each antibiotic in SP-4 broth and 10-B broth and comparing the results with published MICs for this strain. MICs determined in 10-B broth for erythromycin were affected most. This study shows that the activities of sparfloxacin and PD 127391 are similar to one another and comparable or superior to those of other drugs used to treat mycoplasmal infections. The MICs of both new quinolones were consistently 2 to several dilutions lower than those of ciprofloxacin for each species.     

In-vitro activity of trospectomycin sulphate against Mycoplasma and Ureaplasma species isolated from humans

Trospectomycin sulphate, a novel analogue of spectinomycin, was compared to spectinomycin, tetracycline, lincosamide, macrolide, quinolone and naphthalenic ansamycin-class antibiotics for in-vitro activity against Mycoplasma pneumoniae, M. hominis and Ureaplasma urealyticum. MIC determinations were conducted by the agar dilution method using either SP-4 (Mycoplasma spp.) or A8 (U. urealyticum) agars. Trospectomycin compared favorably with tetracycline for all the strains of M. pneumoniae, M. hominis or U. urealyticum tested. Ciprofloxacin was the most active of the newer quinolones tested. Trospectomycin was as active as this quinolone antibiotic, or more active, in vitro. Other antibiotics such as the macrolides and lincosamides were highly active against one or more of the three mycoplasma groups tested but none was active against all three. The results suggest that trospectomycin may be useful in the treatment of mycoplasma-induced respiratory or genital tract infections in man.     

泌尿生殖道支原体感染检测及药敏试验

目的了解本地区泌尿生殖道解脲脲原体（Uu）和人型支原体（Mh）的感染状况及药物敏感性,指导临床医生合理应用抗生素。方法应用法国生物梅里埃公司提供的IST试剂盒进行支原体鉴定及9种药物敏感检测,并对结果进行统计学分析。结果2410例门诊患者中检出支原体阳性者共1401例,总感染率为58．1％,其中Uu单独感染901例（占37．4％）,Mh感染85例（占3．5％）,Uu＋Mh混合感染415例（占17．2％）。交沙霉素和原始霉素敏感率最高,对Uu感染分别是98．8％和98．8％,对Uu＋Mh混合感染分别为86．9％和86．8％;环丙沙星敏感率最低,分别是6．4％和2．6％。结论支原体感染以Uu为主,交沙霉素和原始霉素敏感率最高,环丙沙星敏感率最低。临床应选用培养敏感的抗菌药物,提高治疗效果。