Ofloxacin for the treatment of leprosy

Among the major commercially available fluoroquinolones, ciprofloxacin was inactive against M. leprae in mice; pefloxacin was active, 50 mg/kg daily showed bacteriostatic activity but 150 mg/kg daily displayed bactericidal activity; ofloxacin was more active than pefloxacin, 50 mg/kg daily exerted the same level of bactericidal effect as pefloxacin 150 mg/kg daily, and ofloxacin 150 mg/kg displayed profound killing activity. Two clinical trials with 6 months of pefloxacin and/or ofloxacin in 31 previously untreated lepromatous patients have been completed. Pefloxacin 400 mg twice daily or 800 mg once daily or ofloxacin 400 mg once daily were equally effective; definite clinical improvement with drastically decrease of morphological index to the baseline were observed in all patients at 2 months after beginning of treatment; about 99.99%, or 4 "logs", of organisms viable on Day 0 were killed by 22 doses of either pefloxacin or ofloxacin. The side effects from the two trials were rare and mild, and the patients tolerated extremely well the combinations of pefloxacin/ofloxacin plus multidrug therapy (MDT) regimen for multibacillary leprosy recommended by WHO. The amount of rifampicin-resistant mutants in lepromatous patients before treatment are no more than 4 "logs", thus, all rifampicin-resistant mutants may be eliminated by 22 doses of either pefloxacin or ofloxacin. It is, therefore, possible that the combination of ofloxacin and rifampicin may considerably shorten the required duration of MDT.     

Human pancreatic tissue concentration of bactericidal antibiotics.

Pancreatic infection represents the most important cause of fatal outcome in human acute pancreatitis. In a comparative analysis, human pancreatic tissue concentrations of 10 different bactericidal antibiotics were determined in 89 patients undergoing pancreatic surgery. Concentrations of the antibiotics were determined in the blood and pancreatic tissue using high-pressure liquid chromatography. Pancreatic tissue concentrations 120 minutes after intravenous administration were as follows: mezlocillin, 19.0 mg/kg; piperacillin, 20.3 mg/kg; cefotaxime, 9.1 mg/kg; ceftizoxime, 7.9 mg/kg; netilmicin, 0.4 mg/kg; tobramycin, 0.4 mg/kg; ofloxacin, 1.7 mg/kg; ciprofloxacin, 0.9 mg/kg; imipenem, 6.0 mg/kg; metronidazole, 3.5 mg/kg. Three groups of antibiotics were established: group A, substances with low tissue concentrations (netilmicin, tobramycin), which were below the minimal inhibitory concentrations of most bacteria found in pancreatic infection; group B, antibiotics with pancreatic tissue concentrations which were sufficient to inhibit some but not all bacteria in pancreatic infection (mezlocillin, piperacillin, ceftizoxime, cefotaxime); group C, substances with high pancreatic tissue levels as well as high bactericidal activity against most of the germs present in pancreatic infection (ciprofloxacin, ofloxacin, imipenem). These data could serve as the basis for adequate antibiotic prophylaxis or treatment of pancreatic infection.     

Combination therapy with ciprofloxacin plus azlocillin against Pseudomonas aeruginosa: effect of simultaneous versus staggered administration in an in vitro model of infection

The effect of dose scheduling on the pharmacodynamics of simulated human doses of ciprofloxacin (200 mg intravenously [iv] every 12 h) and azlocillin (4 g iv every 12 h) alone or in combination against Pseudomonas aeruginosa was studied in a two-compartment in vitro kinetic model of infection. Studies with the two drugs in combination were compared using simultaneous or staggered (first doses of each drug were administered 6 h apart) dosing schedules. Bacterial regrowth and resistance were prevented by all combination dosing schedules; however, the simultaneous regimen consistently provided the greatest extent of killing for all strains, particularly in those initially resistant to ciprofloxacin. These enhanced effects of the combination were corroborated by an increase in the peak and duration of bactericidal activity in the analogous "serum" compartment of the model. These data show the potential usefulness of simultaneous dosing of an antipseudomonal beta-lactam with ciprofloxacin against P. aeruginosa.     

Fieber und Lymphadenopathie

We report on 4 patients with different types of tularemia acquired in Switzerland or nearby countries. All patients presented with fever, moderate to highly elevated signs of inflammation, and local lymphadenopathy. Additionally, 3 patients did not respond to empirical antimicrobial therapy with aminopenicillins. A tick bite was identified as mode of transmission in 2 patients, while 1 patient showed a possible connection to a tick bite. The route of transmission for the fourth patient remained unknown. The diagnosis of tularemia was either based on positive serology, on a positive polymerase chain reaction (PCR) from the lymph node samples or on positive blood cultures. The treatment in adult patients was ciprofloxacin 500–750 mg twice daily orally for 3 weeks. The pediatric patient was treated with gentamicin 4 mg/kg i.v. once daily for 1 week and ciprofloxacin 15 mg/kg twice daily orally for another 2 weeks. All patients recovered completely. Due to the increasing incidence of tularemia in Switzerland, this infection should be considered in patients with fever and lymph node enlargement particularly after tick bite. We recommend treatment with ciprofloxacin orally for 14–12 days.     

粪肠球菌感染抗菌药物联合应用的体外效应研究

目的　评价万古霉素、奈替米星、阿米卡星、环丙沙星、左氧氟沙星和加替沙星 6种抗菌药物分别与第一代头孢菌素头孢硫脒联合用药 ,对于临床分离的粪肠球菌 (Enterococcusfaecalis,Ef)的体外联合抗菌效应。方法　采用棋盘法设计 ,微量肉汤稀释法测定。测定不同浓度组合的 6组抗菌药物对 30株临床分离的革兰阳性球菌的最低抑菌浓度 ,并计算FIC指数。FIC≤ 0 .5为协同作用 ,0 .5 2为拮抗作用。结果　头孢硫脒对粪肠球菌的MIC50 为 2～ 8mg L ,与万古霉素、奈替米星、阿米卡星、环丙沙星、左氧氟沙星、加替沙星联合应用后 ,其MIC50 分别显著地降低至 0 .1 2 5 ,0 .2 5 ,0 .2 5 ,0 .2 5 ,0 .2 5 ,0 .2 5mg L。FIC指数分布 :FIC≤ 0 .5占 50 %～ 86 .7% ;0 .5 2为 0。结论　 6种抗菌药物与头孢硫脒分别联合用药后 ,对粪肠球菌基本表现为协同作用和相加作用 ,并以协同作用为主 ,无关作用较少 ,无拮抗作用     

Failure of ciprofloxacin to eradicate convalescent fecal excretion after acute salmonellosis: experience during an outbreak in health care workers

OBJECTIVE: To determine the efficacy of ciprofloxacin therapy in eradicating convalescent fecal excretion of salmonellae after acute salmonellosis. DESIGN: Randomized, placebo-controlled, double-blind trial of ciprofloxacin, with prospective follow-up of nonparticipants. SETTING: An acute care community hospital experiencing an outbreak of salmonellosis. PATIENTS: Twenty-eight health care workers developed acute infection with Salmonella java; 15 participated in a placebo-controlled trial of ciprofloxacin, beginning on day 9 after infection. INTERVENTIONS: Eight patients were randomly assigned to receive ciprofloxacin, 750 mg, and 7 patients to receive placebo; both were administered orally twice daily for 14 days. Nonparticipants who received therapy were placed on the same ciprofloxacin regimen. MEASUREMENTS AND MAIN RESULTS: Study participants had follow-up stool cultures every 3 days initially and then weekly for 3 weeks; nonparticipants were followed until three consecutive cultures were negative. All eight ciprofloxacin recipients showed eradication of S. java from stool cultures within 7 days of beginning therapy (compared with 1 of 7 placebo recipients), and their stool cultures remained negative up to 14 days after discontinuing therapy (P less than 0.01). However, 4 of 8 relapsed; their stool cultures became positive between 14 and 21 days after therapy. In addition, 3 of 3 hospitalized patients treated with ciprofloxacin who did not participate in the controlled trial also relapsed. Thus, the total relapse rate was 7 of 11 (64%; 95% CI, 31% to 89%). In 4 of these 7 patients, relapse was associated with a longer duration of fecal excretion of salmonellae than that of the placebo group. Relapse could not be explained on the basis of noncompliance, development of resistance, or presence of biliary disease. CONCLUSIONS: Despite its excellent antimicrobial activity against salmonellae and its favorable pharmacokinetic profile, ciprofloxacin at a dosage of 750 mg orally twice daily had an unacceptably high failure rate in patients with acute salmonellosis and may have prolonged fecal excretion of salmonellae. The late occurrence of relapses indicates the need to obtain stool cultures up to 21 days after therapy to document fecal eradication in acute salmonellosis.     

The early bactericidal activity of rifabutin measured by sputum viable counts in Hong Kong patients with pulmonary tuberculosis.

Previously untreated patients with smear-positive pulmonary tuberculosis were randomly allocated to treatment with 600, 300, 150 or 75 mg doses of rifabutin (LM427, ansamycin), 600, 300 or 150 mg of rifampicin, 300 mg isoniazid or to no drug daily for 2 days. The fall in viable counts of Mycobacterium tuberculosis in sputum collections during the 2 days, termed the early bactericidal activity (EBA), was estimated from counts of colony-forming units (cfu) on selective 7H-11 agar medium. The EBA for rifabutin ranged from -0.039 (an increase in counts) to 0.049 log10 cfu/ml/day whereas the EBA increased from 0.071 for 150 mg rifampicin to 0.293 log10 cfu/ml/day for 600 mg rifampicin and was 0.43 log10 cfu/ml/day for 300 mg isoniazid. The difference between the EBAs for rifabutin and rifampicin just attained significance (P = 0.05) suggesting that rifabutin was inactive or less active than rifampicin against the extracellular bacilli in pulmonary cavities. Peak plasma concentrations of rifabutin after the initial doses were found to be proportional to dose size and were approximately 7 times lower than those after the same dose size of rifampicin. The lower EBA of rifabutin as compared to rifampicin is probably due to the low plasma concentrations which are not fully compensated for by slightly greater antituberculosis activity of rifabutin in vitro.     

Multiple combination bactericidal antibiotic testing for patients with cystic fibrosis infected with multiresistant strains of Pseudomonas aeruginosa

We developed a rapid in vitro antibiotic susceptibility test to screen double- and triple-antibiotic combinations for bactericidal activity against 75 multiresistant Pseudomonas aeruginosa isolates referred from 44 cystic fibrosis (CF) patients. When used alone, the most effective intravenous antibiotic, meropenem, was bactericidal against only 44% of the isolates. High-dose tobramycin (200 microg/ml; concentrations achievable by aerosol administration) was bactericidal against 72% of isolates. Adding a second antibiotic significantly improved bactericidal activity. The most effective double-antibiotic combinations contained high-dose tobramycin plus meropenem, piperacillin/tazobactam, or ciprofloxacin, and were bactericidal against 88 to 94% of the isolates. Excluding high-dose tobramycin, the most effective intravenous double-antibiotic combinations contained meropenem plus ciprofloxacin, tobramycin (4 microg/ml), or cefipime, and were bactericidal against 85%, 71%, and 70% of isolates, respectively. Adding a third antibiotic did not significantly improve inhibition in vitro. We conclude that double-antibiotic combinations containing meropenem or high-dose tobramycin show the best bactericidal activity in vitro against multiresistant strains of P. aeruginosa. Addition of a third antibiotic to these double-antibiotic combinations may be unnecessary.     

Further studies of the killing of M. leprae by aminoglycosides: reduced dosage and frequency of administration

The bactericidal activity of the aminoglycoside antibiotics streptomycin and kanamycin for Mycobacterium leprae in mice was assessed, both alone and in combination with rifampin, utilizing various dosage schedules. As in previous studies, 100 mg/kg five times weekly of streptomycin and kanamycin resulted, respectively, in 96% +/- 2% and 89% +/- 6% bactericide. Reducing the dosage of streptomycin to 50 mg/kg, 25 mg/kg, and even 12.5 mg/kg resulted in less but significant bactericidal activity. Such a reduction of kanamycin dosage resulted in no significant bactericidal activity. Reducing the frequency of administration of streptomycin (100 mg/kg) to twice weekly and once weekly resulted in a decreased but still significant killing of M. leprae; for kanamycin such a reduction in frequency of administration resulted in loss of bactericidal activity. Streptomycin when combined with rifampin was found more bactericidal than either drug alone, even when each was administered only once monthly.     

Disinfection of water of remove Legionella species: evaluation of an antimicrobial ceramic

To evaluate the efficacy of an antimicrobial ceramic for killing Legionella strains in vitro, bacteria were exposed to the ceramic soaked in PBS at 25 degrees C or 42 degrees C. The number of L. pneumophila began to decrease significantly after 4 h of exposure at 25 degrees C and reached < 10 log cfu/ml after 12 h. A similar significant decrease was also observed after exposure at 42 degrees C. Furthermore, it was found that the antimicrobial ceramic showed bactericidal activity against six strains of Legionella isolated from various water sources, including L. pneumophila (serotype 1-4), L. micdadei, and L. dumoffii, after 24 h of exposure. The antimicrobial activity against L. pneumophila of the supernatant obtained by soaking the ceramic in PBS for 24 h was also assessed. Bactericidal activity of this supernatant was also noted. Analysis of the supernatant by ICP-MS resulted in the detection of eight metals (Mg, Al, Ca, Mn, Zn, Sr, Ag, and Ba) at a maximum concentration of 2.5 mg/l. When reconstituted PBS was made with all eight metals at the same concentrations as in the supernatant, the reconstituted PBS containing Ag alone and all metals showed significantly bactericidal activity against L. pneumophila, but PBS with only one metal component except Ag or a combination of Ag with Zn and/or Ca did not. These findings suggest that the antimicrobial ceramic possesses strong bactericidal activity against Legionella species and that eight metals released from the ceramic have a synergistic bactericidal effect against Legionella. When the antimicrobial ceramic was placed in hot spring water or cooling tower water instead of PBS, the number of L. pneumophila in the water decreased to < 10 log cfu/ml after 24 h of exposure and the bactericidal activity persisted for 5 weeks. These results indicate that the antimicrobial ceramic can be used to eradicate Legionella species contaminating various water sources.     

Killing by antimycobacterial agents of AIDS-derived strains of Mycobacterium avium complex inside cells of the mouse macrophage cell line J774

The murine macrophage continuous cell line J774 was used to measure the ability of antimicrobial agents, either singly or in combination, to kill intracellular Mycobacterium avium complex. All of 14 strains of M. avium complex, isolated from patients with AIDS, grew inside J774 cells during an incubation period of 7 days. The susceptibility of macrophage-ingested M. avium complex to antimicrobial agents was determined by comparing the number of colony-forming units (cfu) of M. avium complex inside untreated macrophages at the time of drug addition with the number of cfu present in macrophages after treatment with drugs for 7 days. Simultaneous experiments were carried out in broth medium without macrophages in order to compare killing of free mycobacteria with killing of macrophage-ingested mycobacteria. Antimicrobial agents (rifampin, rifabutin [Ansamycin], ethambutol, ciprofloxacin, clofazimine, isoniazid, and amikacin) were tested using concentrations that are achievable in the serum of patients. Among drugs known to penetrate macrophages, there was 96.2% agreement in susceptibility test results between the broth experiments and the J774 experiments when single drugs were tested, but only 74% agreement when combinations of drugs were tested. Killing of M. avium complex inside J774 cells by any single drug was uncommon. However, killing in J774 cells occurred against 10 of 11 (91%) strains with the combination of rifabutin + ethambutol + ciprofloxacin and against all of seven strains tested with the combination of rifabutin + ethambutol + amikacin. Interpretive criteria of in vitro susceptibility data need to be developed so that these interpretations correlate with a predictable clinical response in patients.     

Ciprofloxacin once daily versus twice daily for the treatment of pulmonary tuberculosis

Summary Ciprofloxacin was used as an antituberculous drug in adult patients who could not tolerate standard regimens or had to be treated with alternative combinations for resistance problems. During October 1986 to December 1991, 241 patients received ciprofloxacin in two daily 500 mg doses administered under supervision at 8.30 a.m. and 5 p.m., respectively. This group of patients was submitted to retrospective analysis for tolerability and clinical as well as microbiological efficacy. In January 1992, a once daily regimen with 1,000 mg of ciprofloxacin was introduced in order to simplify drug administration together with the other combination partners and to take advantage of higher drug levels at the site of infection. These patients were followed prospectively for safety and efficacy. Until July 1993, 227 patients with smear-positive pulmonary tuberculosis were included in this open study. Comparative analysis was carried out for a selected group of patients who had remained smear and culture positive for more than 27 days after start of treatment. Fifty-four patients who had received ciprofloxacin twice daily and 35 patients on the once daily regimen were evaluable. Both regimens were equally well tolerated. The once daily regimen was associated with a trend towards earlier conversion to smear negativity and a significantly shorter time to culture negativity. Smears became negative on average within 84 days with the once daily and in 94 days with the twice daily schedule (p=0.19). Culture negativity occurred at 60 and 76 days in the respective groups (p=0.0013; log Rank test). Of the patients who received ciprofloxacin twice daily, 33% were still smear and culture positive 90 days after start of treatment compared to only 15% of the patients treated with the once daily schedule. We conclude that ciprofloxacin, given as a single daily dose of 1,000 mg is as safe as two 500 mg doses, more convenient to apply and probably more efficacious.     

Amikacin, ceftazidime, and flucloxacillin against suspended and adherent Pseudomonas aeruginosa and Staphylococcus epidermidis in an in vitro model of infection.

Bacterial inocula were exposed as suspended cultures or as adherent biofilms on glass beads in a novel in vitro model of infection to oscillating drug concentrations mimicking human serum kinetics during clinical treatment. Amikacin was given once or thrice daily alone or in combination with ceftazidime or flucloxacillin against Pseudomonas aeruginosa or Staphylococcus epidermidis. Killing of adherent bacteria was significantly reduced during single-drug treatment compared with suspended bacteria (P less than .001), and beta-lactams were more active than amikacin against both suspended and adherent bacteria (P less than .01). Amikacin-beta-lactam combinations killed the inocula more rapidly and were consistently bactericidal against both suspended and adherent pathogens (P less than .05). Once-daily dosing of amikacin produced greater initial killing than thrice daily dosing (P less than .05), but both regimens were similarly effective after 48 h. The differences in antibiotic activity against suspended and adherent bacteria may relate to clinical failures in the treatment of foreign-body infections by bacteria sensitive to the administered antibiotics, as determined by standard susceptibility tests.     

Double-blind trial of naproxen and phenylbutazone in ankylosing spondylitis.

In a double-blind double-placebo crossover study naproxen (500-750 mg daily) was found to be equivalent to phenylbutazone (400-600 mg daily) in the control of disease activity in 20 patients suffering from ankylosing spondylitis during a two times 5-week trial period. No serious side effects were observed during the trial period. Gastric complaints occurred twice as often under phenylbutazone as under naproxen.     

Treatment of Mycobacterium avium complex bacteremia in AIDS with a four-drug oral regimen. Rifampin, ethambutol, clofazimine, and ciprofloxacin. The California Collaborative Treatment Group.

OBJECTIVE: To determine the quantitative microbiologic response and the clinical response of patients with Mycobacterium avium complex bacteremia and AIDS to an oral antimycobacterial regimen. DESIGN: A phase II, multicenter clinical trial. SETTING: Four university-affiliated medical centers. PATIENTS: Forty-one patients with HIV infection who had at least two consecutive blood cultures positive for M. avium complex and who had not received previous antimycobacterial therapy were enrolled in the study. Thirty-one patients were evaluable with regard to the efficacy of the oral regimen. INTERVENTIONS: Patients received a combination of orally administered rifampin (600 mg), ethambutol (15 mg/kg body weight), clofazimine (100 mg once daily), and ciprofloxacin (750 mg twice daily) for 12 weeks. Parenterally administered amikacin, 7.5 mg/kg daily for 4 weeks after the first 4 weeks of oral therapy, was used at the discretion of the individual investigator. MEASUREMENTS: Clinical symptoms, Karnofsky scores, and adverse events were monitored. Colony counts for M. avium complex were determined. MAIN RESULTS: The mean logarithmic (log) baseline colony count decreased from 2.1 to 0.7 after 4 weeks of oral therapy (P less than 0.001). Suppression of bacteremia was sustained throughout therapy. Thirteen patients (42%) became culture negative during therapy. The mean duration of treatment was 9.7 weeks. Nineteen evaluable patients (61%) completed 12 weeks of therapy. Adverse reactions to one or more agents were common. CONCLUSIONS: A rapid reduction in symptoms and bacteremia can be achieved as early as week 2 of therapy using an oral regimen of rifampin, ethambutol, clofazimine, and ciprofloxacin. Colony counts rose dramatically after therapy was discontinued, suggesting that more prolonged periods of therapy are necessary to eradicate systemic infection.     

Inhibitory action of flurbiprofen and mopidamole on tumor lung metastasis formation in mice

Flurbiprofen, 0.25 mg/kg, administered to mice orally once daily during 3 days prior to an iv transplantation of Lewis lung carcinoma cells, protected 50%-57% of experimental animals from the formation of lung tumor colonies. With the daily dose of 1.0 mg/kg, this effect was less pronounced. Mopidamole, twice daily 90 mg/kg orally during 3 days, did not have this effect.     

Ciprofloxacin decreases the rate of ethanol elimination in humans

BACKGROUND: Extrahepatic ethanol metabolism is postulated to take place via microbial oxidation in the colon, mediated by aerobic and facultative anaerobic bacteria. AIMS: To evaluate the role of microbial ethanol oxidation in the total elimination rate of ethanol in humans by reducing gut flora with ciprofloxacin. METHODS: Ethanol was administered intravenously at the beginning and end of a one week period to eight male volunteers. Between ethanol doses volunteers received 750 mg ciprofloxacin twice daily. RESULTS: A highly significant (p=0.001) reduction in the ethanol elimination rate (EER) was detected after ciprofloxacin medication. Mean (SEM) EER was 107.0 (5.3) and 96.9 (4.8) mg/kg/h before and after ciprofloxacin, respectively. Faecal Enterobacteriaceae and Enterococcus sp. were totally absent after medication, and faecal acetaldehyde production capacity was significantly (p<0.05) decreased from 0.91 (0.15) to 0.39 (0.08) nmol/min/mg protein. Mean faecal alcohol dehydrogenase (ADH) activity was significantly (p<0. 05) decreased after medication, but ciprofloxacin did not inhibit human hepatic ADH activity in vitro. CONCLUSIONS: Ciprofloxacin treatment decreased the ethanol elimination rate by 9.4%, with a concomitant decrease in intestinal aerobic and facultative anaerobic bacteria, faecal ADH activity, and acetaldehyde production. As ciprofloxacin has no effect on liver blood flow, hepatic ADH activity, or cytochrome CYP2E1 activity, these effects are probably caused by the reduction in intestinal flora.     

Effect of daptomycin, metronidazole and mezlocillin combinations on mixed bacterial cultures involving facultative and anaerobic bacteria.

The in vitro activities of different daptomycin concentrations in combination with metronidazole (4 mg/l) or/and mezlocillin (8 mg/l) were investigated on mixed bacterial cultures involving gram-positive facultative cocci. Bacteroides fragilis group strains and Escherichia coli. When Streptococcus faecalis alone or together with E. coli was cultured with B. thetaiotaomicron the colony counts of the latter were 4 log units higher after incubation in the presence of daptomycin and metronidazole than when it was cultured alone. After the addition of mezlocillin, this effect disappeared and all 3 strains were killed. When the same antibiotic combinations were used in the presence of beta-lactamase producing Staphylococcus aureus, the activity of mezlocillin was decreased significantly. The colony counts of the co-cultured B. thetaiotaomicron and E. coli proved to be 2 log and 6 log higher, respectively, than those observed after they were cultured alone. The antimicrobial susceptibilities of the clinical isolates tested here in mixed cultures of up to 3 strains were modified significantly by interactions between the strains and the antibiotics used.     

Comparative activity of daptomycin and teicoplanin against enterococci isolated from blood and urine

The authors compared the activity of daptomycin with that of ampicillin, penicillin, teicoplanin and vancomycin against 304 strains of Enterococcus species isolated from blood and urine. Daptomycin was as active as penicillin against Enterococcus faecalis: 90% of strains were inhibited by 2 mg/L. Daptomycin was more active than vancomycin (90% minimal inhibitory concentration [MIC(90)] 2 mg/L; 90% minimal bactericidal concentration [MBC(90)] 8 mg/L) but was less active than teicoplanin (MIC(50) 0.25; MBC(90) 8 mg/L) or ampicillin (MIC(90) 1 mg/L; MBC(90) 2 mg/L) against E faecalis. In time-kill studies daptomycin was not more rapidly bactericidal than ampicillin or penicillin but was significantly more rapidly bactericidal than either teicoplanin or vancomycin. In combination with gentamicin, daptomycin has activity similar to that of penicillin, vancomycin and teicoplanin. Daptomycin may be a suitable alternative to penicillin in patients allergic to penicillins or for the treatment of enterococcal infections caused by beta-lactamase-producing enterococci.