Tetracyclines, chloramphenicol, erythromycin, and clindamycin

The tetracyclines are effective in the treatment of Chlamydia, Mycoplasma pneumoniae, and rickettsial infections and may also be used for gonococcal infections in patients unable to tolerate penicillins. These drugs may cause gastrointestinal irritation, photo-toxic dermatitis, diarrhea, vestibular damage, and hepatotoxicity in pregnant women. Chloramphenicol is used primarily for anaerobic infections, Haemophilus influenzae meningitis, and typhoid fever. The most important toxic effect of chloramphenicol is bone marrow suppression, which can be dose related or idiosyncratic. Erythromycin is the drug of choice for the treatment of infections caused by M. pneumoniae, Legionella species, group A beta-hemolytic streptococci, and Streptococcus pneumoniae. The frequency of serious untoward effects associated with the use of erythromycin is low; epigastric distress may occur. Clindamycin is active against Bacteroides fragilis and other anaerobic microorganisms. Pseudomembranous enterocolitis has developed in as many as 10% of patients taking this drug. The use of clindamycin should be discontinued promptly if diarrhea occurs.     

Comparative penetration of metronidazole, clindamycin, chloramphenicol, cefoxitin, ticarcillin, and moxalactam into bone.

The concentrations of metronidazole, clindamycin, chloramphenicol, cefoxitin, ticarcillin, and moxalactam in the serum, femurs, and scapulae of normal rats were measured microbiologically 0.5, 1, 1, and 4 h after intravenous injection of 15-, 15-, 20-, 40-, 75-, and 30-mg/kg doses of the respective drugs. By 0.5 h metronidazole reached levels of 3.0 micrograms/g in compact femoral bone and 2.7 micrograms/g in cancellous scapular bone. Clindamycin and chloramphenicol reached levels of 8.1 and 6.1 micrograms/g, respectively, at 0.5 h. Cefoxitin penetrated bone to a level of 2.6 micrograms/g, whereas ticarcillin and moxalactam failed to reach significant levels in bone after single intravenous doses.     

Clindamycin, metronidazole, and chloramphenicol.

Clindamycin, metronidazole, and chloramphenicol are three antimicrobial agents useful in the treatment of anaerobic infections. Clindamycin is effective in the treatment of most infections involving anaerobes and gram-positive cocci, but emerging resistance has become a problem in some clinical settings. Metronidazole is effective in the treatment of infections involving gram-negative anaerobes, but it is unreliable in the treatment of gram-positive anaerobic infections and is ineffective in treating aerobic infections. Additionally, metronidazole is often the drug of choice in treating infections in which Bacteroides fragilis is a serious concern. Chloramphenicol is effective in the treatment of a wide variety of bacterial infections, including serious anaerobic infections, but is rarely used in Western countries because of concerns about toxicity, including aplastic anemia and gray baby syndrome.     

Influence of metronidazole, chloramphenicol, clindamycin and penicillin G on growth and neuraminidase activity of Bacteroides fragilis

The effects of subinhibitory concentrations of metronidazole, chloramphenicol, clindamycin and penicillin G on cell growth and neuraminidase activity of Bacteroides fragilis were tested in six strains from clinical specimens and two type collection strains. All showed significant inhibition of cell growth at one half the MIC after 24 h incubation. Metronidazole at one quarter the MIC was significantly inhibitory after 24 and 48 h incubation. The neuraminidase activity remained unaltered, in comparison with controls, when metronidazole and clindamycin were tested. Chloramphenicol reduced the enzyme activity at both one half and one quarter the MIC. On the other hand, penicillin G enhanced the neuraminidase activity, although the difference was not statistically significant. These in-vitro effects may simulate the behaviour of the bacteria in abscesses in vivo.     

Correlation between serogroup and susceptibility to chloramphenicol, clindamycin, erythromycin, rifampicin and tetracycline among 308 isolates of Clostridium difficile

The susceptibility to chloramphenicol, clindamycin, erythromycin, rifampicin and tetracycline of 308 isolates of Clostridium difficile from various origins was determined by a disc diffusion susceptibility testing and the results were compared with the serogroup of the strains. For the five antimicrobials, there was a clear-cut separation between susceptible and resistant strains. Some correlation between resistance and serogroup was found. Almost all of the 161 isolates of serogroups A, F, G, H and X were susceptible to all antibiotics. The 32 toxigenic isolates of serogroup C were characterized by a typical resistance pattern which could be used for typing purposes. Other serogroups showed variable patterns. The review of 64 cases of antibiotic associated diarrhoea showed that these differences in susceptibility could have clinical implications: all seven cases due to clindamycin were caused by a clindamycin resistant strain of serogroup C, whereas cases associated with other antibiotics were distributed among various serogroups.     

Transferable resistance to clindamycin, erythromycin, and tetracycline in Clostridium difficile

Resistance to clindamycin, erythromycin, and streptogramins in Clostridium difficile could be transferred to a susceptible strain by mixed culture at low frequencies (1 × 10⁻⁸ to 4 − 10⁻⁸ per donor cell). Transfer of tetracycline resistance occurred at frequencies of 3 × 10⁻⁷ to 5 × 10⁻⁷. No plasmid DNA involved in these transfers could be detected.     

Pharmacokinetics and serum bactericidal activities of quinolones in combination with clindamycin, metronidazole, and ornidazole.

To enhance the antimicrobial spectrum of the quinolones against anaerobic organisms and gram-positive bacteria, we investigated in two studies the parenteral combinations of ciprofloxacin (200 mg) and ofloxacin (200 mg) with metronidazole (500 mg) or clindamycin (600 mg) and the oral combinations of enoxacin (400 mg) and fleroxacin (400 mg) with metronidazole (400 mg), clindamycin (300 mg), or ornidazole (500 mg) (only with fleroxacin). The pharmacokinetics and serum bactericidal activities (SBAs) against 5 aerobic and 2 anaerobic species (total, 58 strains) were determined in two groups of 10 healthy volunteers by using a randomized crossover study design. The additions of metronidazole, clindamycin, and ornidazole did not affect the pharmacokinetics of the quinolones. The combination of clindamycin with ciprofloxacin, ofloxacin, and, to a lesser extent, fleroxacin resulted in an increase of the SBA against gram-positive strains (mean peak titers): Staphylococcus aureus, ciprofloxacin alone, 1:5.5; ciprofloxacin-clindamycin, 1:19.9; ofloxacin alone, 1:3.6; ofloxacin-clindamycin, 1:17.5; fleroxacin alone, 1:4.3; fleroxacin-clindamycin, 1:8.1; Streptococcus pneumoniae (fleroxacin and enoxacin were not tested), ciprofloxacin alone, 1:2.0; ciprofloxacin-clindamycin, 1:53; ofloxacin alone, 1:2.6; and ofloxacin-clindamycin, 1:49.2. The high SBA of quinolones against gram-negative bacteria was not affected by the combinations; however, relatively low activities against Pseudomonas aeruginosa were detected. In general, against anaerobic bacteria, low bactericidal activities were determined in both studies (mean peak titers ranged from 1:2.1 to 1:3.1; mean trough titers range from 1:2.0 to 1:2.9). In clinical settings with severe mixed infections, a parenteral therapy consisting of modern quinolones together with clindamycin or imidazole derivatives seems to be active and offers no obvious interactions.     

In vitro evaluation of CP-62,993, erythromycin, clindamycin, and tetracycline against Chlamydia trachomatis.

The antimicrobial activity of CP-62,993 against four Chlamydia trachomatis isolates was compared with those of erythromycin, clindamycin, and tetracycline. The MIC of CP-62,993 was 0.26 to 1.02 micrograms/ml for 100% inclusion inhibition and 0.031 to 0.063 microgram/ml for 50% inclusion inhibition. With pharmacokinetic and antimicrobial studies demonstrating prolonged half-life and in vitro effectiveness, CP-62,993 may make possible a single, short-course treatment regimen for C. trachomatis infection.     

In vitro susceptibilities of Entamoeba histolytica to azithromycin, CP-63,956, erythromycin, and metronidazole.

Current therapy of Entamoeba histolytica infection requires use of multiple agents effective at different body sites, including the intestinal lumen, intestinal tissue, and liver. Azithromycin and CP-63,956, new extended-half-life macrolides which reach high levels in tissue, exhibit in vitro antiamebic activity at 18 or 48 h of incubation at concentrations comparable to that of erythromycin and slightly higher than that of metronidazole. Azithromycin and CP-63,956 have the potential to be useful therapeutic agents for all types of E. histolytica infection.     

Penetration of clindamycin, cefoxitin, and metronidazole into pelvic peritoneal fluid of women undergoing diagnostic laparoscopy.

A single dose of clindamycin, cefoxitin, or metronidazole was administered to each of 30 women. The mean concentration of cefoxitin in pelvic fluid at 1 h exceeded those of the other two drugs (P less than 0.007). Cefoxitin concentrations were inferior to those of the other drugs when compared with the published MIC for 90% of Bacteroides fragilis strains.     

Impact of phenoxymethylpenicillin, erythromycin, clindamycin and doxycycline on Streptococcus salivarius in the oropharynx

Streptococcus salivarius plays a role in the normal oropharyngeal resistance to colonization with group A streptococci. Suppression of Str. salivarius may increase the risk of colonization. Ten subjects were given phenoxymethylpenicillin, ten were given erythromycin, ten were given clindamycin and ten were given doxycycline for seven days. The numbers of Str. salivarius in the oral cavity were determined before, during and after the administration periods. Phenoxymethylpenicillin and doxycycline only slightly suppressed the numbers of Str. salivarius, while erythromycin and clindamycin markedly decreased the numbers. In four and five subjects respectively, Str. salivarius could no longer be isolated after seven days of the drug administration.     

Interactions of ciprofloxacin with clindamycin, metronidazole, cefoxitin, cefotaxime, and mezlocillin against gram-positive and gram-negative anaerobic bacteria.

A total of 598 clinical isolates of anaerobic bacteria were tested against ciprofloxacin by the agar dilution technique with 10(5) CFU on Wilkins-Chalgren medium. Selected strains representative of the six major genera of anaerobes relatively resistant to the quinolones were tested for interactions with ciprofloxacin in combination with clindamycin, metronidazole, cefoxitin, cefotaxime, or mezlocillin by using a checkerboard agar dilution technique. Cefotaxime-ciprofloxacin and clindamycin-ciprofloxacin were the most effective combinations, with 16% of all isolates and 44% of the Bacteroides fragilis group isolates responding synergistically to the former combination and 9% of all isolates and 37% of Peptostreptococcus isolates responding synergistically to the latter. Occasional synergy was seen with all other antibiotic combinations except for metronidazole-ciprofloxacin. Likewise, synergism was seen with all groups of anaerobes except for Fusobacterium species. Antagonistic interactions were observed only with a Peptostreptococcus intermedius strain tested against clindamycin-ciprofloxacin. These data suggest that combinations of ciprofloxacin with these agents may be useful for certain resistant anaerobic infections.     

Anti-anaerobic activity of levofloxacin alone and combined with clindamycin and metronidazole

Microdilution MICs of levofloxacin against twelve anaerobes ranged between 0.5-8.0 microg/ml and those of clindamycin and metronidazole between 0.008-2.0 and 0.25->16.0 microg/ml, respectively. Combination of levofloxacin with clindamycin and/or metronidazole in time-kill tests led to synergy at levofloxacin concentrations at or below the MIC in 7/12 strains.     

Effect of clindamycin, erythromycin, lincomycin, and tetracycline on growth and extracellular lipase production by propionibacteria in vitro.

Two propionibacteria identified as Propionibacterium acnes and Propionibacterium granulosum were grown anaerobically in the presence of growth subinhibitory concentrations (0.25 and 0.5 minimal inhibitory concentrations) of clindamycin, erythromycin, lincomycin, and tetracycline. Viable counts and assays of extracellular lipase were performed on samples taken at 24-h intervals over a 96-h period. The results showed that lincomycin and clindamycin could inhibit the production of the enzyme by both strains with little effect on their growth rates. Tetracycline caused inhibition of lipase production by P. granulosum only. Although production of the enzyme by P. acnes was delayed in the presence of tetracycline, the final titer was the same as the control. Erythromycin had little effect on growth and enzyme production of either strain. It is possible, therefore, that certain antibiotics used in acne therapy may act not only as bactericidal agents but also as inhibitors of enzyme production under non-growth-limiting conditions.     

金黄色葡萄球菌对红霉素和克林霉素诱导耐药分析

目的探讨金黄色葡萄球菌临床分离株对红霉素和克林霉素的耐药性,检测红霉素对克林霉素诱导耐药的发生率。方法采用美国临床实验室标准化研究所（CLSI）推荐的纸片扩散法,检测耐甲氧西林金黄色葡萄球菌（MRSA）以及金黄色葡萄球菌对红霉素和克林霉素的耐药性,并以双纸片法（即D试验）分析红霉素对克林霉素诱导耐药表型。结果金黄色葡萄球菌中MRSA占77.2%。金黄色葡萄球菌对红霉素及克林霉素同时耐药菌株占62.4%,红霉素耐药而克林霉素敏感菌株占21.5%。红霉素耐药而克林霉素敏感的MRSA和甲氧西林敏感金黄色葡萄球菌（MSSA）中D试验阳性分别为72.0%和57.1%。D试验阳性占红霉素耐药而克林霉素敏感金黄色葡萄球菌的68.8%。结论临床微生物实验室应常规开展D试验,检测金黄色葡萄球菌中红霉素对克林霉素的诱导耐药性,以指导临床医师合理选用大环内酯类、林可酰胺类抗菌药物。     

In vitro activity of a new macrolide, A-56268, compared with that of roxithromycin, erythromycin, and clindamycin.

A new macrolide (A-56268) was found to be approximately twice as active as erythromycin and four to eight times more active than roxithromycin. All three macrolides were similar in their potency against anaerobes. Human plasma enhanced the antistaphylococcal activity of A-56268 and erythromycin but reduced the activities of roxithromycin and clindamycin.