Liposome-entrapped ampicillin in the treatment of experimental murine listeriosis and salmonellosis.

The tissue distribution of ampicillin entrapped in liposomes was studied in normal noninfected mice and showed that ampicillin concentrated mostly in the liver and spleen. Liposomate ampicillin was significantly more effective than free ampicillin in reducing splenic and hepatic bacterial counts in C57BL/Ka nude mice chronically infected with Listeria monocytogenes EGD. It was also significantly more effective than free ampicillin in reducing mortality in C57BL/6 mice acutely infected with Salmonella typhimurium C5. Comparison of the results with those previously obtained in the same experimental models with the same amounts of ampicillin bound to polyisohexylcyanoacrylate nanoparticles showed that liposomes were more effective than nanoparticles (M. Youssef, E. Fattal, M. J. Alonso, L. Roblot-Treupel, J. Sauzières, C. Tancrède, A. Omnès, P. Couvreur, and A. Andremont, Antimicrob. Agents Chemother. 32:1204-1207, 1988) in targeting ampicillin to the spleen but were less effective than nanoparticles in targeting ampicillin to the liver and reducing mortality in acute salmonellosis.     

Comparative efficacies of ciprofloxacin, ampicillin and chloramphenicol in treatment of experimental Haemophilus influenzae pneumonia

An experimental murine model of bacteraemic Haemophilus influenzae pneumonia was used to evaluate the therapeutic efficacy of ciprofloxacin, as compared with ampicillin and chloramphenicol. An ampicillin-sensitive (AS) and an ampicillin-resistant (AR) challenge strain were employed. Ciprofloxacin treatment produced intrapulmonary killing of H. influenzae which was superior to that achieved with ampicillin (P less than 0.001, both strains) and chloramphenicol (P less than 0.001, strain AS; P less than 0.005, strain AR). Likewise, survival from strain AS pneumonia was 61% in the ciprofloxacin-treated animals, as compared with 43% for the chloramphenicol-treated, and 22% for the ampicillin-treated groups. We conclude that ciprofloxacin may be an effective agent in treating pneumonia caused by either ampicillin-sensitive or ampicillin-resistant strains of H. influenzae.     

Pharmacokinetics of cefamandole and ampicillin in experimental meningitis.

The penetration of cefamandole and ampicillin into the cerebrospinal fluid of rabbits with and without pneumococcal meningitis was evaluated. In normal animals, a mean maximum concentration of 0.22 +/- 0.13 microgram of cefamandole per ml was measured in the spinal fluid after a dose of 150 mg/kg given intramuscularly; with 25 and 50 mg/kg doses, no antibiotic was detected in the cerebrospinal fluid. With ampicillin, in intramuscular doses of 200 and 300 mg/kg, the mean maximum concentrations encountered in the cerebrospinal fluid were 1.59 +/- 0.4 and 1.47 +/- 0.44 microgram/ml, respectively. Penetration of cefamandole, and to a lesser extent ampicillin, was increased after 24 h of experimental meningitis. With cefamandole, the concentration of drug in the cerebrospinal fluid exceeded the usual inhibitory concentration for Haemophilus influenzae only with the 150 mg/kg dose. After 48 h of meningitis, there was a trend toward higher levels of antibiotic in the cerebrospinal fluid, but the difference between animals infected 24 versus 48 h was not statistically significant. In animals with meningitis, serum concentrations after 150 mg of cefamandole per kg and both ampicillin doses studied were 32 to 38% lower than the serum levels achieved in normal rabbits after identical doses of antibiotic.     

Clindamycin versus ampicillin in the treatment of odontogenic infections

The subjects were 106 patients, aged 14 to 70 years, with acute facial or oral abscesses originating from an odontogenic source. They were randomly assigned to receive 150 mg of clindamycin or 250 mg of ampicillin orally four times daily for seven days. After seven days of treatment, the infections were eradicated in 36 of the 52 clindamycin-treated patients and in 42 of the 54 ampicillin-treated patients, and improved in 16 and 11, respectively. One of the ampicillin group was a treatment failure. Mixed bacterial infections were found in most of the patients; 385 isolates were identified, 167 aerobes and 218 anaerobes. The most common aerobes were Staphylococcus aureus (in 58 patients), Staphylococcus epidermidis (in 47), and Staphylococcus viridans (in 32); the most common anaerobes were species of Peptococcus (in 76), Bacteroides (in 38), and Peptostreptococcus (in 33). No isolates were resistant to clindamycin; nine of 126 aerobes and six of 160 anaerobes were resistant to ampicillin. It is concluded that clindamycin is a safe and effective alternative antibiotic in the treatment of odontogenic infections.     

Furazolidone versus ampicillin in the treatment of traveler''s diarrhea.

Ninety-four U.S. students who acquired diarrhea in Mexico were treated with furazolidone (47 subjects) or ampicillin (47 subjects) on a double-blind random basis. Of 47 students, 26 (55%) who received furazolidone (100 mg four times daily for 5 days) recovered from illness within 48 h after initiation of therapy, in contrast to 15 of 47 (32%) who received ampicillin (500 mg four times daily for 5 days) (P less than 0.05). Altogether, 74% of students treated with furazolidone and 49% of those receiving ampicillin were well within 72 h (P less than 0.05). When furazolidone was compared with ampicillin, clinical illness was shortened on the average from 65 to 61 h for enterotoxigenic Escherichia coli diarrhea, from 83 to 58 h for shigellosis, from 82 to 51 h for diarrhea unassociated with a detectable agent, and from 72 to 57 h for all cases irrespective of etiology. Although not dramatically effective in the current trial, the broad spectrum of activity of furazolidone is of interest. Because of in vitro activity against Campylobacter strains and known effectiveness in treating giardiasis, furazolidone should be considered in therapy for diarrhea of unknown etiology in certain settings when laboratory processing of stools for etiological agent is not feasible.     

Comparison of cotrimoxazole, ampicillin, and chloramphenicol in treatment of experimental Haemophilus influenzae type B meningitis.

To evaluate cotrimoxazole in the treatment of bacterial meningitis, we compared its action with that of ampicillin and chloramphenicol in experimental Haemophilus influenzae type b meningitis. Both trimethoprim and sulfamethoxazole penetrated well into the cerebrospinal fluid of infected rabbits, reaching 40 and 26%, respectively, of their simultaneous serum levels. Levels measured 30 and 60 min after intravenous injection exceeded the minimum inhibitory concentration of this combination for H. influenzae by 10- to 100-fold. The mean ratio of trimethoprim to sulfamethoxazole in cerebrospinal fluid was 1:22. Cotrimoxazole was as effective as ampicillin in therapy of beta-lactamase-negative H. influenzae meningitis and as effective as chloramphenicol for a beta-lactamase positive strain. These findings corroborate favorable preliminary clinical experience reported by others and indicate that cotrimoxazole deserves further study in the therapy of bacterial meningitis.     

Quantitative PCR assay to evaluate ampicillin, ofloxacin, and doxycycline for treatment of experimental leptospirosis

The susceptibility of Leptospira interrogans serovar icterohaemorrhagiae strain Verdun to selected antibiotics used in medical practice (ampicillin, doxycycline, and ofloxacin) was evaluated in a Syrian hamster model, to determine the efficacy of these antibiotics during the course of the disease. A quantitative PCR assay was used to monitor the density of leptospires in blood and in target organs (liver, kidney, lung, heart, and spleen). Our results demonstrated the ability of ampicillin at a high dose (100 mg/kg of body weight) to clear leptospires from the host, except from kidneys and heart, where 10(2) leptospires/g remained at day 6. Ofloxacin (30 mg/kg) was unable to clear bacteria from blood or kidneys. With doxycycline (10 mg/kg), the clearance of leptospires occurred in 2 days in all the target organs studied, with the exception of liver, which required 3 days. Our data demonstrate the value of monitoring the kinetics of experimental leptospiral infection in order to accurately evaluate the efficacy of antibiotics. We have demonstrated the potential value of doxycycline for the treatment of leptospirosis cases, except in circumstances where it is contraindicated. This experimental model could be used to define better therapeutic strategies for human leptospirosis, by testing associations or new formulations of antibiotics.     

Ceftriaxone in the treatment of acute and subacute human brucellosis

A total of 14 adults were diagnosed as having brucellosis by clinical means, serology and blood culture. The first patient to be treated failed to respond to 2 g/day intravenous ceftriaxone, therefore, subsequent patients were treated intravenously, twice daily with 2 g ceftriaxone. Immediate clinical response was seen in nine (69.2%) of the patients. Therapy was changed to tetracycline plus streptomycin in the remaining four (30.8%) patients because of lack of response after 5 days. It is concluded that ceftriaxone may be considered a second-line therapy for brucellosis in patients who cannot be given conventional therapy. Further evaluation of ceftriaxone, either alone or preferably in combination with streptomycin or rifampicin on a larger scale, is indicated.     

Efficacy of ampicillin plus ceftriaxone in treatment of experimental endocarditis due to Enterococcus faecalis strains highly resistant to aminoglycosides

The purpose of this work was to evaluate the in vitro possibilities of ampicillin-ceftriaxone combinations for 10 Enterococcus faecalis strains with high-level resistance to aminoglycosides (HLRAg) and to assess the efficacy of ampicillin plus ceftriaxone, both administered with humanlike pharmacokinetics, for the treatment of experimental endocarditis due to HLRAg E. faecalis. A reduction of 1 to 4 dilutions in MICs of ampicillin was obtained when ampicillin was combined with a fixed subinhibitory ceftriaxone concentration of 4 micrograms/ml. This potentiating effect was also observed by the double disk method with all 10 strains. Time-kill studies performed with 1 and 2 micrograms of ampicillin alone per ml or in combination with 5, 10, 20, 40, and 60 micrograms of ceftriaxone per ml showed a > or = 2 log10 reduction in CFU per milliliter with respect to ampicillin alone and to the initial inoculum for all 10 E. faecalis strains studied. This effect was obtained for seven strains with the combination of 2 micrograms of ampicillin per ml plus 10 micrograms of ceftriaxone per ml and for six strains with 5 micrograms of ceftriaxone per ml. Animals with catheter-induced endocarditis were infected intravenously with 10(8) CFU of E. faecalis V48 or 10(5) CFU of E. faecalis V45 and were treated for 3 days with humanlike pharmacokinetics of 2 g of ampicillin every 4 h, alone or combined with 2 g of ceftriaxone every 12 h. The levels in serum and the pharmacokinetic parameters of the humanlike pharmacokinetics of ampicillin or ceftriaxone in rabbits were similar to those found in humans treated with 2 g of ampicillin or ceftriaxone intravenously. Results of the therapy for experimental endocarditis caused by E. faecalis V48 or V45 showed that the residual bacterial titers in aortic valve vegetations were significantly lower in the animals treated with the combinations of ampicillin plus ceftriaxone than in those treated with ampicillin alone (P < 0.001). The combination of ampicillin and ceftriaxone showed in vitro and in vivo synergism against HLRAg E. faecalis.     

Combined action of chloramphenicol and ampicillin on chloramphenicol-resistant Haemophilus influenzae.

Previous studies have demonstrated high, concentration-dependent serum protein binding of cefonicid. To determine the in vivo pharmacokinetic significance of these observations, the pharmacokinetics of both total and unbound (non-protein-bound) cefonicid was studied in six volunteers after a single intravenous dose of 30 mg/kg. Saturable serum protein binding was observed in vivo; the mean +/- standard deviation free fraction of cefonicid was 17.6 +/- 6.1% immediately after administration and declined to a constant value of approximately 2% as total serum concentrations fell below 100 micrograms/ml. This nonlinear binding was associated with a pronounced decline in unbound serum cefonicid concentrations during the first 3 h after administration, with low or undetectable unbound drug concentrations by 12 h. Renal clearance of total cefonicid averaged 21.1 ml/min per kg and did not vary with time; in contrast, the mean +/- standard deviation unbound cefonicid renal clearance increased from 5.7 +/- 2.1 to 10.8 +/- 1.6 ml/min per kg with time (P less than 0.02). This study may partially explain the poor results obtained with single daily dosing of cefonicid in endocarditis. Dosage regimens of certain antimicrobial agents with high, saturable serum protein binding and extensive renal tubular secretion may be most appropriately designed based on unbound drug pharmacokinetics.     

Synergistic action of ampicillin and nafcillin against ampicillin-resistant Haemophilus influenzae.

Six strains of ampicillin-resistant Haemophilus influenzae type b were studied in vitro for synergy between ampicillin and nafcillin. The minimal inhibitory concentrations for these strains with 10(4) colony-forming units per ml were 6.25 to 12.5 microgram of ampicillin per ml and 6.25 to 25 microgram of nafcillin per ml. Studies with these agents demonstrated synergism against all six strains of H. influenzae type b. Most strains were inhibited by 0.78 microgram of nafcillin plus 0.78 microgram of ampicillin per ml. A child with osteomyelitis caused by H. influenzae type b was successfully treated with a combination of ampicillin and nafcillin. These data suggest that further studies assessing the synergistic effect of this drug combination against H. influenzae type b are warranted.     

Effect of nanoparticle-bound ampicillin on the survival of Listeria monocytogenes in mouse peritoneal macrophages.

The efficacy of ampicillin bound to polyisohexylcyanoacrylate nanoparticles was studied in vitro in mouse peritoneal macrophages infected with Listeria monocytogenes. Nanoparticles containing ampicillin 1 mg/L were more effective after 30 h than free ampicillin at the same concentration, with viable counts of 3.68 and 5.43 log10 cfu/mL, respectively. The nanoparticles acted on the intracellular bacteria after a lag period of 6-9 h; this time was apparently required for the degradation of the polymer. At the doses used in these experiments, empty nanoparticles had neither an anti-listeria nor a cytotoxic effect.     

Liquid brucellar allergen in the combined treatment of brucellosis patients]

The efficacy of liquid brucellar allergen (LBA) was studied in 227 brucellosis patients with active infectious process and marked DTH, in need of a pathogenetically based decrease of specific infectious allergic background. The reference group was made up of 140 brucellosis patients given only basic therapy (antibiotics, antiinflammatory and symptomatic agents). The administration of LBA, whose active principle is a polysaccharide and protein complex, reduced high sensitivity to brucellar antigen and raised the functional activity of neutrophilic granulocytes and T-lymphocytes, improved the late results of the treatment of patients with brucellosis running its course with pronounced sensitization.     

Ciprofloxacin versus ampicillin and probenecid in the treatment of uncomplicated gonorrhoea in men

Eighty-six men with uncomplicated gonorrhoea were entered into a study comparing the efficacy of a single oral dose of 250 mg of ciprofloxacin with a single oral dose of ampicillin 2 g and probenecid 1 g for urethral gonorrhoea and a course of ampicillin, 500 mg four times per day for five days in rectal and pharyngeal infection. Two patients were excluded. Of the remaining 84, 45 were treated with ampicillin and 39 with ciprofloxacin. In the ampicillin group there were two treatment failures out of 40 urethral infections. Three patients with rectal infection were cured. Only one patient out of three pharyngeal infections was cured. Ciprofloxacin cured all of 34 urethral and three rectal infections including one penicillinase producing strain of Neisseria gonorrhoeae (PPNG). Four of five pharyngeal infections were cured but there was one treatment failure. There were no major side effects in either treatment group. In conclusion, a single oral dose of 250 mg of ciprofloxacin is an effective treatment for uncomplicated gonorrhoea in men.     

The use of cytoflavin for the treatment of chronic brucellosis

Clinical and pathogenetic efficacy of cytoflavin as a component of combined therapy of chronic brucellosis was tested in 50 patients who repeated its beneficial effect on the quality of life. The mechanism of cytoflavin action consists of lowering severity of endogenous intoxication and systemic inflammation.