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1.  Quinolone accumulation in Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. 
The accumulation of quinolones by Escherichia coli JF568, Pseudomonas aeruginosa PAO1, and Staphylococcus aureus ATCC 29213 was measured by a modified fluorometric assay (J. S. Chapman and N. H. Georgopapadakou, Antimicrob. Agents Chemother. 33:27-29, 1989). The quinolones examined were fleroxacin, pefloxacin, norfloxacin, difloxacin, A56620, ciprofloxacin, ofloxacin, and Ro 09-1168. In all three organisms, uptake was complete in less than 5 min and was proportional to extracellular quinolone concentrations between 2 and 50 micrograms/ml, which is consistent with simple diffusion. Washing cells with quinolone-free buffer decreased accumulation by up to 70% in E. coli and P. aeruginosa but not in S. aureus. Similarly, incubation with the uncouplers 2,4-dinitrophenol and carbonyl cyanide m-chlorophenylhydrazone increased accumulation up to fourfold in E. coli and P. aeruginosa, though not in S. aureus, suggesting endogenous, energy-dependent efflux. High quinolone hydrophobicity was generally associated with decreased accumulation in E. coli and P. aeruginosa (except in the case of pefloxacin) but was associated with increased accumulation in S. aureus (except in the case of difloxacin). Ciprofloxacin had the highest accumulation in E. coli and P. aeruginosa, while pefloxacin had the highest accumulation in S. aureus.
PMCID: PMC192008  PMID: 1416840
2.  Analysis of peptidoglycan precursors in vancomycin-resistant enterococci. 
Analysis by high-pressure liquid chromatography of the cytoplasmic peptidoglycan precursors of a high- and a low-level vancomycin-resistant Enterococcus spp. was performed before and after induction of resistance. This analysis showed a decrease of the D-Ala-D-Ala and UDP-MurNac-pentapeptide pools, an increase of the UDP-MurNac-tripeptide pool, and the appearance of new UDP-MurNac-containing material. These results lead us to suggest that the vancomycin-induced carboxypeptidase activity cleaves the D-Ala-D-Ala (L. Gutmann, D. Billot-Klein, S. Al-Obeid, I. Klare, S. Francoul, E. Collatz, and J. van Heijenoort, Antimicrob. Agents Chemother. 36:77-80, 1992), which in turn would prevent formation of the normal UDP-MurNac-pentapeptide and thereby of the vancomycin target. The novel UDP-MurNac-containing material is thought to correspond to peptidoglycan precursors which might be synthesized by an alternate pathway (T. D. H. Bugg, G. D. Wright, S. Dutka-Malen, M. Arthur, P. Courvalin, and C. T. Walsh, Biochemistry 30:10408-10415, 1991) and which would be unable to bind vancomycin in glycopeptide-resistant enterococci.
PMCID: PMC191609  PMID: 1510445
3.  Efficacies of liposome-encapsulated streptomycin and ciprofloxacin against Mycobacterium avium-M. intracellulare complex infections in human peripheral blood monocyte/macrophages. 
Antimicrobial Agents and Chemotherapy  1992;36(12):2808-2815.
Current treatments of disseminated infection caused by the Mycobacterium avium-M. intracellulare complex (MAC) are generally ineffective. Liposome-mediated delivery of antibiotics to MAC-infected tissues in vivo can enhance the efficacy of the drugs (N. Düzgüneş, V. K. Perumal, L. Kesavalu, J. A. Goldstein, R. J. Debs, and P. R. J. Gangadharam, Antimicrob. Agents Chemother. 32:1404-1411, 1988; N. Düzgüneş, D. A. Ashtekar, D. L. Flasher, N. Ghori, R. J. Debs, D. S. Friend, and P. R. J. Gangadharam, J. Infect. Dis. 164:143-151, 1991). We investigated the therapeutic efficacies of liposome-encapsulated streptomycin and ciprofloxacin against growth of the MAC inside human peripheral blood monocyte/macrophages. Treatment was initiated 24 h after infection of macrophages with the MAC and stopped after 20 h, and the cells were incubated for another 7 days. The antimycobacterial activity of streptomycin was enhanced when the drug was delivered to macrophages in liposome-encapsulated form, reducing the CFU about threefold more than the free drug did throughout the concentration range studied (10 to 50 micrograms/ml). With 50 micrograms of encapsulated streptomycin per ml, the CFU were reduced to 11% of the initial level of infection. Liposome-encapsulated ciprofloxacin was at least 50 times more effective against the intracellular bacteria than was the free drug: at a concentration of 0.1 microgram/ml, liposome-encapsulated ciprofloxacin had greater antimycobacterial activity than the free drug at 5 microgram/ml. With liposome-encapsulated ciprofloxacin at 5 micrograms/ml, the CFU were reduced by more than 1,000-fold at the end of the 7-day incubation period, compared with untreated controls. These results suggest that liposome-encapsulated ciprofloxacin or other fluoroquinolones may be effective against MAC infections in vivo.
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PMCID: PMC245550  PMID: 1482150
4.  Effects of (-)-2'-deoxy-3'-thiacytidine (3TC) 5'-triphosphate on human immunodeficiency virus reverse transcriptase and mammalian DNA polymerases alpha, beta, and gamma. 
(-)-2'-Deoxy-3'-thiacytidine (3TC) is a selective inhibitor of human immunodeficiency virus replication in vitro (J. A. V. Coates, N. Cammack, H. J. Jenkinson, A. J. Jowett, M. I. Jowett, B. A. Pearson, C. R. Penn, P. L. Rouse, K. C. Viner, and J. M. Cameron, Antimicrob. Agents Chemother. 36:733-739, 1992). The effect of 3TC 5'-triphosphate on both the RNA-dependent and DNA-dependent activities of human immunodeficiency virus type 1 reverse transcriptase and DNA polymerases alpha, beta, and gamma from HeLa cells was investigated. 3TC 5'-triphosphate is a competitive inhibitor (with respect to dCTP) of the RNA-dependent DNA polymerase activity (apparent Ki = 10.6 +/- 1.0 to 1.24 +/- 5.1 microM, depending on the template and primer used); the DNA-dependent DNA polymerase activity is 50% inhibited by a 3TC 5'-triphosphate concentration of 23.4 +/- 2.5 microM when dCTP is present at a concentration equal to its Km value. Chain elongation studies show that 3TC 5'-triphosphate is incorporated into newly synthesized DNA and that transcription is terminated in a manner identical to that found for ddCTP. The 50% inhibitory concentrations of 3TC 5'-triphosphate against DNA polymerases alpha, beta, and gamma at concentrations of dCTP equal to the Km were 175 +/- 31, 24.8 +/- 10.9, and 43.8 +/- 16.4 microM, respectively. More detailed kinetic studies with 3TC 5'-triphosphate and DNA polymerases beta and gamma are consistent with the fact that inhibition of these enzymes by 3TC 5'-triphosphate is competitive with respect to dCTP. The values of Ki were determined to be 18.7 microM for DNA polymerase beta and 15.8 +/- 0.8 microM for DNA polymerase gamma.
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PMCID: PMC192031  PMID: 1384425
5.  Use of radioactive ethanolamine incorporation into phospholipids to assess in vitro antimalarial activity by the semiautomated microdilution technique. 
Phospholipid biosynthetic activity is intense in the erythrocytic stage of Plasmodium falciparum because of the parasite's own enzymatic machinery. The incorporation of various labeled phospholipid precursors in comparison with the incorporation of nucleic acid and protein precursors was tested to evaluate P. falciparum growth in vitro. These precursors, namely, [3H]ethanolamine, [3H]hypoxanthine, [3H]palmitate, [14C]serine, [3H]choline, [3H]inositol, and [3H]isoleucine, were all accurate indicators of parasite growth. However, because of its high level of incorporation, [3H]ethanolamine proved to be the best tool for assessing parasite viability. When culture parameters were carefully controlled, [3H]ethanolamine incorporation into phospholipids was proportional to pulse time, precursor concentration, and initial parasitemia and was sensitive to the number of uninfected erythrocytes (hematocrit). It can be used for a wide range of infected erythrocytes, from 2 x 10(4) to 5 x 10(5). The use of [3H]ethanolamine for in vitro antimalarial drug screening is a good alternative to the method of Desjardins et al. (R. E. Desjardins, C. J. Canfield, J. D. Haynes, and J. D. Chulay, Antimicrob. Agents. Chemother. 16:710-718, 1979). The major advantage is that the culture medium can be supplemented with hypoxanthine, which results in better parasite growth. [3H]ethanolamine is also an ideal tool when compounds that interfere with DNA and/or RNA metabolism are to be investigated for their effect on Plasmodium growth.
PMCID: PMC189224  PMID: 1590699
14.  Saperconazole therapy in a rabbit model of invasive aspergillosis. 
Antimicrobial Agents and Chemotherapy  1992;36(12):2681-2685.
The efficacy of orally and intravenously administered saperconazole against Aspergillus fumigatus was assessed in an immunosuppressed temporarily leukopenic rabbit model of invasive aspergillosis and compared with that of amphotericin B. Oral saperconazole at dosages of 5, 10, and 15 mg/kg of body weight per day improved survival compared with that of controls. In addition, saperconazole at 10 and 15 mg/kg/day reduced the tissue burden and reduced levels of circulating antigen, which correlated with increasing dosages of saperconazole. Intravenous saperconazole produced levels in serum more than 10-fold that of oral therapy. Intravenous saperconazole not only improved survival and reduced antigen levels but also significantly eradicated A. fumigatus from tissues compared with those of controls and was as effective as amphotericin B in these studies. Saperconazole was effective in the treatment of experimental invasive aspergillosis and demonstrates the potential of the newer azoles in therapy for invasive aspergillosis.
PMCID: PMC245528  PMID: 1482137
15.  Daptomycin or teicoplanin in combination with gentamicin for treatment of experimental endocarditis due to a highly glycopeptide-resistant isolate of Enterococcus faecium. 
Antimicrobial Agents and Chemotherapy  1992;36(12):2611-2616.
Using an experimental endocarditis model, we studied the activity of daptomycin used alone or in combination with gentamicin against an Enterococcus faecium strain that was highly resistant to glycopeptides and susceptible to gentamicin. In vitro, the MIC of daptomycin was 1 micrograms/ml. In vivo, daptomycin appeared to be effective only when it was used in a high-dose regimen, i.e., 12 mg/kg of body weight every 8 h (-2.5 log10 CFU/g versus controls; P < 0.05), particularly when it was combined with gentamicin (-5.0 log10 CFU/g versus controls; P < 0.01). Since the distribution of daptomycin into cardiac vegetations, as evaluated by autoradiography, appeared to be homogeneous, the poor in vivo activity of daptomycin was considered to be related to its high degree of protein binding, as suggested by killing curves studies. Since the MIC of teicoplanin for the vancomycin-resistant E. faecium strain used in the study was only 64 micrograms/ml and since an in vitro synergy between teicoplanin at high dose and gentamicin was observed, a high-dose regimen of teicoplanin, i.e., 40 mg/kg every 12 h, was also assessed in vivo. This treatment provided marginal activity only when it was combined with gentamicin (-2.3 log10 CFU/g versus controls; P < 0.05). These results suggest that the levels of daptomycin or teicoplanin in serum required to cure experimental endocarditis caused by a highly glycopeptide-resistant strain of E. faecium would not be achievable in humans.
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PMCID: PMC245515  PMID: 1336339
16.  In vitro and in vivo activities of DQ-2556 and its mode of action. 
Antimicrobial Agents and Chemotherapy  1992;36(12):2595-2601.
DQ-2556 is a recently developed cephalosporin with a broad spectrum of antibacterial activity against both gram-positive and gram-negative bacteria. Its in vitro activity was roughly comparable to those of cefuzonam and cefpirome and greater than those of ceftazidime, cefepime, and cefclidin against gram-positive bacteria. Against gram-negative bacteria, DQ-2556 showed almost the same activity as those shown by cefpirome and cefepime. The activity was largely unaffected by culture medium pH or the addition of human serum. The protective effect of DQ-2556 in experimental gram-positive pathogen and Escherichia coli infections in mice was greater than those of ceftazidime, cefuzonam, cefepime, and cefclidin and was similar to that of cefpirome. Against Pseudomonas aeruginosa and Acinetobacter calcoaceticus infections, DQ-2556 was more active than cefuzonam and had activity similar to or less than those of ceftazidime, cefpirome, cefepime, and cefclidin. When cells of E. coli were exposed to various concentrations of DQ-2556, filamentous cells were observed at concentrations of 0.0008 micrograms/ml and greater, spheroplasts started to form at 0.025 micrograms/ml, and subsequent cell lysis was observed. The affinity of DQ-2556 to PBP 3 of E. coli, which participates in septum formation, as suggested by morphological observation, was two times greater than that of ceftazidime. DQ-2556 also had high affinities for PBPs 1B and 1A of E. coli. These results suggest that DQ-2556 is worthy for subsequent clinical trials.
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PMCID: PMC245513  PMID: 1482128
17.  Pharmacokinetics of R 82913 in AIDS patients: a phase I dose-finding study of oral administration compared with intravenous infusion. 
Antimicrobial Agents and Chemotherapy  1992;36(12):2661-2663.
The pharmacokinetics of oral administration of R 82913, or tetrahydroimidazol [4,5,1-jk]-benzodiazepin-2(1H)-one or -thione (TIBO), was compared with those of intravenous administration in five AIDS patients. TIBO was administered as a single daily 1-h infusion of 100 mg for 29 days and orally as a single daily dose for 14 days with three consecutive regimens of 100, 200, and 100 mg with probenecid (1 g) daily. Each cycle was followed by a wash-out period. Oral bioavailability of TIBO appears to be low and is not improved by the adjunction of probenecid. Trough levels obtained with oral administration systematically remained far below the 90% inhibitory concentration of TIBO against human immunodeficiency virus type 1 (HIV-1). Tolerance of TIBO was excellent. No clinical efficacy could be demonstrated. p24 antigenemia decreased significantly in one patient under intravenous therapy. TIBO derivatives are promising anti-HIV-1 agents in vitro, but improvement of oral bioavailability is needed before implementation of long-term efficacy and tolerability studies. Moreover, rapid emergence of resistance, which has been recently documented, constitutes a major problem with most nonnucleoside reverse transcriptase inhibitors.
PMCID: PMC245524  PMID: 1482134
18.  Prospective observational study of Klebsiella bacteremia in 230 patients: outcome for antibiotic combinations versus monotherapy. 
Antimicrobial Agents and Chemotherapy  1992;36(12):2639-2644.
Combination antimicrobial agent therapy has been advocated for treatment of gram-negative bacteremia, including that caused by Klebsiella spp. We performed a prospective, observational, 10-hospital collaborative study to evaluate the efficacy of antibiotic combination therapy versus that of monotherapy for 230 consecutive patients with Klebsiella bacteremia. The species involved were K. pneumoniae (82%), K. oxytoca (15%), and K. ozaenae (0.4%). Of the bacteremias, 26% were polymicrobial in nature. A total of 53% of cases were nosocomial infections. The most common portals were the urinary tract (28%), biliary tract (12%), lung (10%), and abdomen (9%). Some 49 and 51% of the patients had received monotherapy and antibiotic combination therapy (beta-lactam plus aminoglycoside), respectively; 14-day mortalities in the two groups were 20 and 18%, respectively. However, for the subgroup of patients who experienced hypotension within 72 h prior to or on the day of the positive blood culture, those patients who received combination therapy experienced significantly lower mortality (24%) than did those who received monotherapy (50%). We conclude that monotherapy with an antibiotic that is active in vitro against Klebsiella (beta-lactam or aminoglycoside) is sufficient therapy for less severely ill patients (immunocompetent, urinary tract portal, mentally alert, normal vital signs). On the other hand, for severely ill patients who experience hypotension, antibiotic combination therapy with a beta-lactam and an aminoglycoside agent is preferred.
PMCID: PMC245520  PMID: 1482131
19.  Interleukin-1-induced nonspecific resistance to bacterial infection in mice is not mediated by glucocorticosteroids. 
Antimicrobial Agents and Chemotherapy  1992;36(12):2785-2789.
Preexposure to a low dose of interleukin-1 (IL-1; 3 to 30 micrograms/kg) 24 h before a lethal gram-negative bacterial infection prolonged survival in normal and granulocytopenic mice. To examine whether this protective effect is mediated by glucocorticosteroids, we first measured corticosterone concentrations in mice after administration of 80 and 800 ng of IL-1. IL-1 induced a dose-dependent increase in corticosterone levels in plasma. Next, the corticosterone peak induced by a protective dose of IL-1 (800 ng) was simulated by administration of synthetic human adrenocorticotropic hormone 1-24 (ACTH) in normal and neutropenic mice. Although corticosterone levels induced by pretreatment with IL-1 or ACTH were virtually identical, the ACTH-induced corticosterone peak was not associated with protection against Klebsiella pneumoniae infection in normal mice and Pseudomonas aeruginosa infection in neutropenic mice. This indicates that the protective effect of IL-1 pretreatment against gram-negative bacterial infection is not mediated by elevated levels of glucocorticosteroids. In addition, we found that plasma corticosterone concentrations during K. pneumoniae infection were significantly lower after pretreatment with IL-1 than after pretreatment with ACTH or vehicle, probably reflecting the better physical condition of IL-1-treated mice.
PMCID: PMC245545  PMID: 1482145
20.  Antibacterial properties of Ro 40-6890, a broad-spectrum cephalosporin, and its novel orally absorbable ester, Ro 41-3399. 
Antimicrobial Agents and Chemotherapy  1992;36(12):2825-2834.
Ro 41-3399 is a novel orally active ester of Ro 40-6890, an aminothiazolyl cephalosporin with potent in vitro activities against commonly encountered aerobic gram-positive bacteria (streptococci and methicillin-susceptible staphylococci) and gram-negative bacteria (members of the family Enterobacteriaceae, haemophili, meningococci, and gonococci). In terms of the MICs determined by the methods recommended by the National Committee for Clinical Laboratory Standards, for 50 and 90% of gram-positive organisms, the water-soluble free carboxylic acid Ro 40-6890 proved to be at least as active as or two- to fourfold more active than cefpodoxime, cefuroxime, cefaclor, amoxicillin, amoxicillin-clavulanic acid, and ceftriaxone; against aerobic gram-negative organisms, Ro 40-6890 was usually two- to fourfold more active than cefpodoxime, the next most potent of the oral drugs under comparison, but remained usually two- to fourfold weaker than ceftriaxone. Ro 40-6890 showed a high affinity for the essential penicillin-binding proteins of susceptible bacteria and was resistant to hydrolysis by a broad array of beta-lactamases. Ro 41-3399 bopentil was well absorbed in mice when administered by oral gavage and proved effective in several experimental bacterial infections. Further studies with Ro 41-3399 and Ro 40-6890 are in progress.
PMCID: PMC245553  PMID: 1482153
21.  In vitro activities of Ro 40-6890 against 164 predominantly intestinal members of the families Enterobacteriaceae and Vibrionaceae. 
Antimicrobial Agents and Chemotherapy  1992;36(12):2835-2838.
The in vitro activities of Ro 40-6890, the active metabolite of a novel orally absorbable cephalosporin ester, Ro 41-3399, against 164 nonfastidious aerobic gram-negative rods of predominantly intestinal origin from patients with diarrhea were evaluated by the agar dilution method recommended by the National Committee for Clinical Laboratory Standards. Ro 40-6890 was inhibitory (MIC for 90% of isolates [MIC90], 0.12 micrograms/ml) against the majority of intestinal members of the families Enterobacteriaceae and Vibrionaceae (Vibrio spp., Aeromonas spp., and Plesiomonas shigelloides). The potency of Ro 40-6890 was very similar to that of cefotaxime (MIC90, 0.12 micrograms/ml) and distinctly higher than those of cefadroxil (MIC90, > or = 128 micrograms/ml) and amoxicillin-clavulanic acid (MIC90, 32 micrograms/ml-2 micrograms/ml).
PMCID: PMC245554  PMID: 1482154
23.  Optimal dosing of trimethoprim-sulfamethoxazole when used with loperamide to treat traveler's diarrhea. 
Antimicrobial Agents and Chemotherapy  1992;36(12):2821-2824.
To explore the optimal dosing regimen for trimethoprim-sulfamethoxazole (TMP-SMX) when used in combination with loperamide to treat traveler's diarrhea, 190 U.S. adults with acute diarrhea were enrolled in a double-blind, randomized trial in Guadalajara, Mexico. All patients received loperamide (4-mg loading dose; 2 mg after each loose stool, not to exceed 16 mg/day for 3 days) and were randomized to receive a 3-day course of TMP-SMX (160:800 mg twice daily for six doses) (group A), a single large dose of TMP-SMX (320:1,600 mg) (group B), or a large loading dose (320:1,600 mg) followed by standard doses for 3 days (160:800 mg twice daily for five doses) (group C). Patients in group C responded best (P < 0.01), with 75% of subjects recovered from diarrhea in 12 h compared with 34 h (group A) and 33 h (group B). Similar differences in favor of group C were noted in the subset of patients who presented with moderate to severe diarrhea. On average, patients in group C took significantly (P < 0.05) less loperamide (1.2 mg) after the 4-mg loading dose compared with patients in group A (2.4 mg) or group B (2.0 mg). We conclude that the most efficacious treatment of traveler's diarrhea in the interior of Mexico is to take loperamide in usual doses to control symptoms in combination with a single large dose of TMP-SMX, which should then be continued for 3 days in standard doses.
PMCID: PMC245552  PMID: 1482152
24.  Pharmacodynamics of once-daily amikacin in various combinations with cefepime, aztreonam, and ceftazidime against Pseudomonas aeruginosa in an in vitro infection model. 
Antimicrobial Agents and Chemotherapy  1992;36(12):2741-2746.
The pharmacodynamics of once-daily amikacin administered as monotherapy and in combination with aztreonam, ceftazidime, and cefepime against Pseudomonas aeruginosa ATCC 27853 and clinical isolate 16690 (moderately susceptible to ceftazidime) were investigated with an in vitro model of infection over a 24-h period. Monotherapy with aztreonam, ceftazidime, and cefepime and combinations of aztreonam with cefepime or ceftazidime were also studied. MICs and MBCs were determined for viable organisms at 24 h to test for the development of resistance. Once-daily amikacin demonstrated killing activity over the initial 8 h superior to those of all other drugs administered as monotherapy against both strains tested (P < 0.01). Regrowth by 24 h was greatest for the amikacin regimen (P < 0.01) but was apparent for all monotherapy regimens against both strains. No changes in susceptibilities were observed. All combination therapies containing once-daily amikacin achieved 99.9% reductions in log10 CFU/ml by 2.0 h against both strains, with no regrowth of organisms at 24 h. Aztreonam-cefepime and -ceftazidime combinations required approximately 5 to 6 h to achieve a 99.9% reduction in log10 CFU/ml. Although there was no difference in time to the 99.9% kill between the aztreonam-cefepime and -ceftazidime regimens against either strain, the killing activity of these combinations was significantly less than those of regimens containing once-daily amikacin (P < 0.01). Minor differences in the initial susceptibilities of beta-lactams and the monobactam aztreonam against P. aeruginosa may not be important for therapeutic outcomes when used in combination with single-daily aminoglycoside therapy.
PMCID: PMC245538  PMID: 1482142
25.  Relationship between antibiotic concentration in bone and efficacy of treatment of staphylococcal osteomyelitis in rats: azithromycin compared with clindamycin and rifampin. 
Antimicrobial Agents and Chemotherapy  1992;36(12):2693-2697.
We examined the effect of azithromycin (CP-62,993), a new oral macrolide-like antibiotic, alone and in combination with rifampin, as treatment for experimental staphylococcal osteomyelitis. Clindamycin was used as a comparison drug. Rats (n = 10 to 15 per group) were infected by direct instillation of Staphylococcus aureus into the tibial medullary cavity. After 10 days, 21-day treatments with azithromycin (50 mg/kg of body weight, once daily, by the oral route), rifampin (20 mg/kg, once daily, subcutaneously), or clindamycin (90 mg/kg, three times daily, by the oral route) were started. The drugs were used singly or in combination (azithromycin plus rifampin or clindamycin plus rifampin). Peak azithromycin concentrations in bone were > 30 times higher than levels in serum, but the drug had little effect on final bacterial titers (5.13 +/- 0.46 log10 CFU/g of bone; for controls, 6.54 +/- 0.28 log10 CFU/g). Clindamycin was more active than azithromycin (3.26 +/- 2.14 log10 CFU/g of bone; 20% of sterilized bones), but rifampin was the most active single drug (1.5 +/- 1.92 log10 CFU/g; 53% of sterilized bones). Therapy with rifampin or clindamycin alone was associated with the emergence of resistance. Rifampin plus azithromycin (0.51 +/- 1.08 log10 CFU/g of bone; 80% of sterilized bones) and rifampin plus clindamycin (0.87 +/- 1.34 log10 CFU/g of bone; 66% of sterilized bones) were the most active regimens. Thus, azithromycin is ineffective as a single drug for the treatment of experimental staphylococcal osteomyelitis, despite high levels in bone that markedly exceeded the MIC, but it may be an attractive partner drug for rifampin.
PMCID: PMC245530  PMID: 1336342

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