Comparison of ciprofloxacin and rifampicin in experimental Legionella pneumophila pneumonia

We evaluated intraperitoneal ciprofloxacin and rifampicin alone and as combination therapy in experimentally induced Legionella pneumophila pneumonia in guinea pigs. Intraperitoneal treatment began 48 h after intratracheal inoculation of 3 X 10(6) L. pneumophila and consisted of sterile saline (0.3 ml bid), ciprofloxacin (30 mg/kg bid), rifampicin (10 mg/kg/bid), or ciprofloxacin plus rifampicin (same doses). Animals were treated for five days and survivors killed after 11 days. Quantitative lung cultures were done post mortem. Respective mean and median days of animal survival were increased by treatment with ciprofloxacin plus rifampicin (8.4 and 9.5 days), ciprofloxacin (8.2 and 7.5 days), or rifampicin (8.3 and 7.5 days), compared with controls (5.5 and 5.0 days). Compared with control animals (log rank test) survival was improved by treatment with ciprofloxacin plus rifampicin (P less than or equal to 0.047) ciprofloxacin (P less than or equal to 0.047) or rifampicin (P less than or equal to 0.047). Quantitative lung cultures (cfu/g) were also decreased by treatment with ciprofloxacin plus rifampicin (2.0 X 10(4)), ciprofloxacin (5.4 X 10(4)), or rifampicin (1.7 X 10(4)) compared with controls (3.2 X 10(8)). No differences in survival, quantitative lung cultures, or animal weights were noted between treatment groups. This study demonstrates that ciprofloxacin is as effective as rifampicin in the treatment of experimentally induced L. pneumophila pneumonia and that the combination of ciprofloxacin plus rifampicin has no advantages over single agent therapy in this model.     

In vitro activity of gatifloxacin, compared with ciprofloxacin, clarithromycin, erythromycin, and rifampin, against Legionella species

Gatifloxacin, a new advanced-generation, 8-methoxy fluoroquinolone, has shown efficacy against a broad spectrum of microorganisms. In this study, the in vitro activity of gatifloxacin was compared with that of ciprofloxacin, clarithromycin, erythromycin, and rifampin against 214 Legionella spp. Species tested in order of frequency were: L. pneumophila serogroups 1 to 9 (181 strains); L. dumoffii (10 strains); L. micdadei (9 strains); L. longbeachae (7 strains); and other Legionella spp. (7 strains). MICs were determined by a standard dilution procedure using buffered yeast extract agar. Gatifloxacin and rifampin were the most active agents against all strains of Legionella tested. Moreover, against L. pneumophila strains tested, gatifloxacin was found to be more active (highest MIC90 = 0.03 mg/L) than ciprofloxacin (highest MIC90 = 0.06 mg/L) and clarithromycin (highest MIC90 = 0.12 mg/L). L. pneumophila serogroups 1 to 4 and 6 to 9 (MIC90 = 0.016 mg/L) were more susceptible to gatifloxacinthan L. pneumophila serogroup 5 (MIC90 = 0.03 mg/L). The activity of gatifloxacin against L. micdadei was equal to that of ciprofloxacin (MIC90 = 0.016 mg/L) and greater than that of erythromycin (MIC90 = 1.0 mg/L). The activity of gatifloxacin against L. dumoffii and L. longbeachae was equal to that of ciprofloxacin (MIC90 = 0.03 mg/L). The activity of gatifloxacin was similar against isolates obtained from both patients and environmental sources.     

Susceptibility of Shigella species to erythromycin.

Two of the most common causes of inflammatory enteritis are Campylobacter fetus subsp. jejuni and Shigella species. No single antimicrobial agent is recommended for treatment of both diseases. Erythromycin is used to treat C. fetus subsp. jejuni infections but has not been studied in shigellosis. For this reason, we determined the susceptibility of 22 strains of Shigella to erythromycin and found that Shigella species are susceptible to concentrations of erythromycin which are obtainable in stool.     

Sensitivity and resistance of Legionella pneumophila to some antibiotics and combinations of antibiotics

For the treatment of Legionella pneumophila infections erythromycin and rifampicin are the antibiotics of choice. In view of reported therapy failures other antibiotics, e.g. the quinolones, are currently under investigation. The sensitivity of L. pneumophila to four antibiotics and to combinations of antibiotics was investigated and the rate of mutations was calculated. For 20 L. pneumophila strains we determined the MIC of rifampicin (0.002-0.004 mg/l), erythromycin (0.063-0.125 mg/l), norfloxacin (0.125 mg/l) and ciprofloxacin (0.016-0.032 mg/l). Mutation rates ranged from 1 x 10(-8) for ciprofloxacin to greater than 1 x 10(-7) for erythromycin, resulting in high-level resistance to rifampicin in most strains and erythromycin resistance in one strain, but not in resistance to the quinolones. The combination of erythromycin and rifampicin was synergistic (FIC index less than 0.5) against four of the L. pneumophila strains and showed indifference (FIC index 0.5-2.0) for the remainder (mean FIC index 0.79). Combinations of ciprofloxacin and erythromycin and of rifampicin and ciprofloxacin showed only indifference (mean FIC index respectively 1.05 and 1.21). Combining rifampicin with ciprofloxacin was not effective in reducing the number of mutants for either of these antibiotics, whereas the other combinations did prevent this.     

Inactivation of the macrolide antibiotics erythromycin, midecamycin, and rokitamycin by pathogenic Nocardia species.

A survey of five Nocardia spp. with respect to susceptibility towards three macrolides (erythromycin, rokitamycin, and midecamycin) showed that the Nocardia spp. have different susceptibility profiles. Most of the resistance was due to the inactivation of the macrolides by phosphorylation, glycosylation, reduction, deacylation, or a combination thereof.     

临床分离念珠菌对5种常用抗真菌药物的体外敏感试验结果分析

目的　了解临床分离的念珠菌对氟康唑、两性霉素B、氟胞嘧啶、伊曲康唑及酮康唑体外敏感性。方法　采用SensititreYeastOne试验板以微量稀释法测定上述 5种抗真菌药物对临床分离的 10 8株念珠菌最低抑菌浓度 (MIC)。结果　 10 8株念珠菌中达到氟康唑、伊曲康唑、氟胞嘧啶耐药标准的分别有 8株 (7.4%)、15株(13.9%)、2株 (1.9%) ,念珠菌属MIC值分布种间差异较大。白色念珠菌对 5种药物的MIC90 值最低 ,6 0株白色念珠菌中仅 2株耐氟康唑 ,3株耐伊曲康唑 ,对氟胞嘧啶无耐药株 ;光滑念珠菌对氟康唑、伊曲康唑、酮康唑的MIC值分布呈高值 ,10株光滑念珠菌中 4株耐氟康唑 ,3株剂量依赖性敏感 ,7株耐伊曲康唑 ,且吡咯类之间有交叉耐药。其他菌株 ,除季也蒙念珠菌对伊曲康唑有一定的耐药 (2 /6 )外 ,对 5种抗真菌药物的MIC分布均较低。结论　不同念珠菌对常用抗真菌药物敏感性存在差异 ,准确分离鉴定和药敏试验 ,对于指导临床合理选药有重要意义。     

临床分离念珠菌对5种常用抗真菌药物的体外敏感试验结果分析

目的了解临床分离的念珠菌对氟康唑、两性霉素B、氟胞嘧啶、伊曲康唑及酮康唑体外敏感性.方法采用Sensititre YeastOne试验板以微量稀释法测定上述5种抗真菌药物对临床分离的108株念珠菌最低抑菌浓度(MIC).结果 108株念珠菌中达到氟康唑、伊曲康唑、氟胞嘧啶耐药标准的分别有8株(7.4%)、15株(13.9%)、2株(1.9%),念珠菌属MIC值分布种间差异较大.白色念珠菌对5种药物的MIC90值最低,60株白色念珠菌中仅2株耐氟康唑,3株耐伊曲康唑,对氟胞嘧啶无耐药株;光滑念珠菌对氟康唑、伊曲康唑、酮康唑的MIC值分布呈高值,10株光滑念珠菌中4株耐氟康唑,3株剂量依赖性敏感,7株耐伊曲康唑,且吡咯类之间有交叉耐药.其他菌株,除季也蒙念珠菌对伊曲康唑有一定的耐药(2/6)外,对5种抗真菌药物的MIC分布均较低.结论不同念珠菌对常用抗真菌药物敏感性存在差异,准确分离鉴定和药敏试验,对于指导临床合理选药有重要意义.     

Comparative susceptibility of Mycoplasma pneumoniae to erythromycin, ciprofloxacin, and lomefloxacin

Lomefloxacin was found to be comparable to ciprofloxacin in its ability to inhibit the in vitro growth of Mycoplasma pneumoniae (MIC range 2-8 mcg/ml), but it was significantly less active than erythromycin. Although 30 different strains from widely differing geographic areas and isolation time periods were examined, no macrolide-resistant strains were observed.     

Susceptibility of Pseudomonas species to the novel antibiotics mureidomycins.

Strains of Pseudomonas aeruginosa, including imipenem- or ofloxacin-resistant clinical isolates, and some other species in the genus Pseudomonas were inhibited by novel antibiotics of the mureidomycin (MRD) group. On the other hand, almost all other gram-positive and gram-negative bacteria were resistant to MRDs, though the antibiotics potently inhibited the in vitro peptidoglycan synthesis of Escherichia coli and P. aeruginosa. All of the strains in the genus Pseudomonas that were inhibited by less than or equal to 200 micrograms of MRDs per ml were classified into the rRNA groups I and III, and none of the tested strains of rRNA group I were resistant to MRDs, suggesting that these two groups are closely related to each other evolutionary. Among group I strains, P. aeruginosa, P. mendocina, P. stutzeri, and P. alcaligenes were more susceptible than the others, suggesting a closer relationship among these species.     

The antimicrobial activity of ciprofloxacin against Legionella species and the treatment of experimental Legionella pneumonia in guinea pigs

The antimicrobial activity of ciprofloxacin was tested against 15 standard reference strains, and 37 clinical and environmental strains of Legionella pneumophila by an agar dilution method, using a new growth medium (B-SYE agar) which we devised. The minimal inhibitory concentrations of ciprofloxacin were found to be inoculum dependent, and ranged from 0.02 to 0.06 mg/l at 10(4) cfu inoculum and 0.02 by 0.125 mg/l at 10(6) cfu inoculum. The most potent antibacterial activity was shown by rifampicin, followed by ofloxacin, ciprofloxacin, enoxacin, norfloxacin, erythromycin and pipemidic acid in that order. The therapeutic efficacy of ciprofloxacin in experimental guinea pig pneumonia due to L. pneumophila was fairly good with a survival rate of 80%. From other data of ours, its effectiveness in experimental pneumonia was equal to or greater than that of erythromycin. Further studies would be appropriate to investigate the possibility of using ciprofloxacin for the treatment of human L. pneumophila infection.     

葡萄球菌种间对红霉素和克林霉素的诱导耐药性研究

目的了解耐苯唑青霉素葡萄球菌种间对红霉素和克林霉素的诱导耐药性。方法采用琼脂扩散法筛选耐苯唑青霉素葡萄球菌,然后采用双纸片法检测耐药葡萄球菌对红霉素、克林霉素的耐药性。结果160例耐苯唑青霉素葡萄球菌中D试验阳性40株,阳性率为25%,葡萄球菌种间金黄色葡萄球菌和表皮葡萄球菌对红霉素和克林霉素的诱导耐药差异有统计学意义（P〈0.05）。结论葡萄球菌D试验阳性率高达25%,临床应常规进行D试验,以正确指导临床用药。     

Bactericidal activities of five antibiotics during short-term exposure to coagulase-negative staphylococci.

After a 1-h exposure to concentrations used for topical prophylaxis in neurosurgical procedures, bacitracin, vancomycin, and oxacillin were bactericidal against more than 90% of 48 body fluid isolates of coagulase-negative staphylococci. More than 10% of isolates survived despite exposure for 4 h to concentrations of gentamicin and streptomycin greater than those employed for topical prophylaxis.     

Differences in ability of cell-wall antibiotics to suppress emergence of rifampicin resistance in Staphylococcus aureus

Rifampicin resistance developed easily in methicillin-susceptible and methicillin-resistant strains of Staphylococcus aureus during an overnight incubation in broth containing 0.1 mg/l of rifampicin. Incubation of methicillin-susceptible Staph. aureus and 0.1 mg/l of rifampicin with 1 mg/l of nafcillin reduced the emergence of rifampicin resistance with only 5 of 50 strains (10%) becoming rifampicin-resistant. However, incubation of the methicillin-susceptible or methicillin-resistant strains with 0.1 mg/l of rifampicin and 1 mg/l of vancomycin did not prevent the development of rifampicin resistance. Rifampicin resistance developed in 25 of 50 (50%) of methicillin-susceptible and 32 of 50 (64%) methicillin-resistant Staph. aureus strains tested. These data would suggest that differences exist in the abilities of nafcillin and vancomycin to suppress the development of rifampicin resistance in Staph. aureus (P less than 0.01). Caution should be exercised when the combination of vancomycin and rifampicin is used for infections caused by Staph. aureus and Staph. aureus isolates recovered during therapy should be monitored for the development of rifampicin resistance.     

Effects of erythromycin and ciprofloxacin on chronic fecal excretion of Campylobacter species in marmosets.

Ciprofloxacin was compared with erythromycin for the eradication of Campylobacter species that were chronically excreted in the stools of marmosets (Saguinus labiatus labiatus, Saguinus fuscicollis nigrifrons, and Saguinus fuscicollis illigeri). Stool cultures were negative within 48 h of the beginning of treatment with either agent. Within 10 days after the end of therapy, however, Campylobacter species were again isolated from the stools of six animals that had received erythromycin. During an 8-week follow-up period, no animal that had received ciprofloxacin relapsed. High levels of ciprofloxacin in the stool (mean, 49.2 micrograms/g) possibly contributed to the efficacy of this agent.     

Development of quinolone-imipenem cross resistance in Pseudomonas aeruginosa during exposure to ciprofloxacin.

Selection and regrowth of ciprofloxacin-resistant variants, which were present in low frequencies in the initial inoculum, were seen when large inocula of Pseudomonas aeruginosa were incubated with ciprofloxacin. These variants showed cross resistance to other quinolones. In 8 of 13 strains tested, ciprofloxacin selected imipenem-resistant variants in a similar way to imipenem. The opposite phenomenon of ciprofloxacin-imipenem cross resistance after exposure to imipenem was not detected. None of the ciprofloxacin-resistant variants showed cross resistance to aztreonam, piperacillin, or tobramycin. These findings indicate that widespread and uncritical use of ciprofloxacin gives a potential risk of development of resistance in P. aeruginosa not only to quinolones but also to another unrelated useful agent, imipenem. In vitro evaluation of this phenomenon in isolates from patients with P. aeruginosa infections may be justified, since strains differ in development of quinolone-imipenem cross resistance after ciprofloxacin exposure.     

Susceptibility of Mycoplasma pneumoniae to several new quinolones, tetracycline, and erythromycin.

Mycoplasma pneumoniae (39 strains) was most susceptible to two quinolones, WIN 57273 and sparfloxacin, with MICs for 90% of the strains (MIC90S) of 0.125 and 0.25 micrograms/ml, respectively. It was susceptible to ofloxacin and ciprofloxacin at 2 micrograms/ml and to lomefloxacin and fleroxacin at 4 micrograms/ml. The MIC90 of erythromycin was 0.062 microgram/ml, and that of tetracycline was 1 microgram/ml.     

Susceptibility of Campylobacter pyloridis to three macrolide antibiotics (erythromycin, roxithromycin [RU 28965], and CP 62,993) and rifampin.

The presence of Campylobacter pyloridis in the gastric mucosa was recently linked to peptic ulcer disease. This study compared the inhibitory activity of three macrolide compounds (erythromycin, roxithromycin [RU 28965], and CP 62,993) and rifampin against 10 clinical isolates of C. pyloridis. The macrolides were equally effective against the test strains, with MICs ranging from 0.06 to 0.5 microgram/ml; rifampin was less active, with MICs ranging from 0.25 to greater than 1 microgram/ml. Erythromycin and the two new macrolide derivatives are potentially useful agents in the treatment of infections caused by C. pyloridis.