Comparison of Cephalexin, Penicillin V, and Ampicillin in Streptococcal Infections in Monkeys

Intravenous inoculation of a group A hemolytic streptococcus caused lethal infections in all of 11 untreated monkeys. Daily intragastric administration of either 25 or 50 mg per kg per day, given in two equal morning and afternoon doses, yielded similar results in monkeys treated with cephalexin, penicillin V, and ampicillin; all eight monkeys in each therapy group survived. At dose levels of 12.5 mg per kg per day, six of eight, four of eight, and one of eight receiving cephalexin, penicillin V, and ampicillin, respectively, died. The differences observed at the lower dose level between cephalexin and ampicillin could be attributed, in part, to differences in the minimal inhibitory concentrations (MIC) of cephalexin (MIC = 0.24 mug/ml) and ampicillin (MIC = 0.01 mug/ml). The differences in results between penicillin V, which had the same MIC as ampicillin, could perhaps be attributed, in part, to shorter duration of antibacterial activity and higher protein binding of penicillin V. These studies support previous observations that cephalexin at 25 to 50 mg/kg doses is effective in severe streptococcal sepsis in monkeys.     

Psychiatric care and politics.

The minimum inhibitory concentrations (MIC''s) of penicillin, ampicillin, tetracycline, erythromycin, spectinomycin and sulfadiazine were determined for 732 isolates of Neisseria gonorrhoeae collected in 1973-74. Comparison of the results of this survey with data from other Canadian studies showed that the percentage of isolates resistant to tetracycline had not changed since 1966, but that the percentage of erythromycin-resistant isolates had decreased. After an initial increase in 1966 the percentage of penicillin-resistant isolates stabilized. Spectinomycin-resistant isolates were not found. Positive correlations were observed between the MICs of the antibiotics tested; the highest positive correlations were between penicillin and ampicillin and between penicillin and tetracycline. A positive correlation was also noted between penicillin resistance and increasing spectinomycin MICs. Finally, a significant seasonal variation in MICs was found, the trend being towards increasing MICs during the summer.     

The ineffectiveness of tobramycin combination therapy in Streptococcus faecium endocarditis.

A patient required mitral valve replacement following ineffective antibiotic treatment of enterococcal endocarditis caused by Streptococcus faecium. Endocarditis had relapsed despite therapy with ampicillin and tobramycin for six weeks. A second relapse had occurred following treatment with penicillin and gentamicin. Initial failure of antibiotic therapy may be related to the known lack of in vitro and in vivo synergy between penicillin and tobramycin against S. faecium. Effective therapy of enterococcal endocarditis requires considerations of bacterial speciation, determination of high-level aminoglycoside resistance, and preferably adequate antibiotic synergy studies to assure effective therapy.     

Treatment of Salmonella Enteritis and its Effect on the Carrier State

During an outbreak of Salmonella enteritis, 113 symptomatic and asymptomatic patients were assigned to different treatment groups: 43 received ampicillin; 41 were given trimethoprim-sulfamethoxazole; and 29 received no specific therapy. During the four-week observation period no statistically significant benefit from treatment with either ampicillin or trimethoprim-sulfamethoxazole was apparent in relation to duration and severity of symptoms or duration of the carrier state. However, the impression that trimethoprim-sulfamethoxazole might have shortened the period of fecal Salmonella excretion in the few asymptomatic patients may warrant further controlled studies.There was no significant alteration in hematological or biochemical values, or urine constituents, in patients receiving trimethoprim-sulfamethoxazole. Side effects probably attributable to this drug developed in only 5% of the 41 patients.It is concluded that uncomplicated salmonellosis is best treated without using currently available chemotherapeutic agents.     

Therapy of Anorectal Gonorrhea in Men: Efficacy of Oral Antibiotic Regimens

The results of therapy in 916 men with anorectal gonorrhea treated with orally given antibiotic drugs were reviewed retrospectively. There was a 17.8 percent failure rate for tetracycline (total dose, 10 grams) and a 10.7 percent failure for 3.5 grams of ampicillin plus 1 gram of probenicid. Repeating the ampicillin plus probenicid dose once in 8 to 14 hours reduced the failure rate to 1.6 percent, an efficacy comparable to the regimen of 4.8 million units of aqueous procaine penicillin G given intramuscularly plus 1 gram of probenicid given orally for treatment of anorectal gonorrhea.     

Comparison of amoxicillin and ampicillin in single-dose oral treatment of males with gonococcal urethritis

Amoxicillin in single oral doses of 2.0 g, 2.0 g plus 1.0 g probenecid, or 3.0 g was compared with ampicillin 3.5 g plus 1.0 g probenecid in the treatment of 203 males with uncomplicated acute gonococcal urethritis. Cure rates above 95% were produced by all treatments except the 2.0-g amoxicillin dose, which cured 89% of patients. Of 198 pretreatment gonococcus isolates tested by an agar dilution technique for susceptibility to penicillin G, ampicillin and amoxicillin, over 50% showed relative resistance (MIC > 0.06 μg/ml) to the antibiotics. However, amoxicillin was somewhat more active against isolates showing considerable resistance (MIC ≥ 1.0 μg/ml) to penicillin G or ampicillin. Adverse effects of amoxicillin were few: two patients reported transient nausea and six noted short-lived diarrhea. No hypersensitivity reactions were observed.     

Single-dose treatment of gonococcal urethritis in males: evaluation of procaine penicillin,ampicillin and spectinomycin

Males with acute gonococcal urethritis were treated at random with 2.4 million units aqueous procaine penicillin G intramuscularly plus 1.0 g. probenecid orally, 3.5 g. ampicillin orally plus 1.0 g. probenecid orally, or 2.0 g. spectinomycin intramuscularly. The overall follow-up was 97%. All treatments were of equal efficacy, eradication of gonococcal disease being observed in 93 to 97% of treated patients. Treatment failures occurred in each drug group and pre-treatment isolates recovered from these cases showed decreased susceptibility to the agent used. Aqueous procaine penicillin G plus probenecid remains the preferred therapy for gonorrhea. For patients hypersensitive to penicillin, spectinomycin is currently a reasonable alternative drug. This agent, unlike procaine penicillin-probenecid, is probably ineffective against concurrent incubating syphilis, and future development of bacterial resistance is a definite possibility.     

Preliminary characterization of a food-borne multiple-antibiotic-resistant Salmonella typhimurium strain

Plasmid characterization studies were conducted on a Salmonella typhimurium strain isolated from pasteurized milk and from a symptomatic patient during the 1985 Illinois salmonellosis outbreak. This strain (Hf) was reported to possess an unusual plasmid profile which distinguished it from all Salmonella strains isolated in the United States prior to 1984. Antibiotic susceptibility testing revealed that the strain was resistant to tetracycline, erythromycin, clindamycin, sulfisoxazole, sulfadiazene, triple sulfa, cefoperazone, streptomycin, mezlocillin, piperacillin, carbenicillin, penicillin, ampicillin, and kanamycin. Plasmid analysis revealed that the strain possessed four plasmids with sizes of approximately 158, 98, 10.2, and 6.0 kilobase pairs (kb). Successive transfer at 43 degrees C led to increased antibiotic sensitivity in 75.5% of the isolates screened. Electroporation and calcium chloride treatment were each used to transform plasmid-free Escherichia coli strains with the plasmid pool from S. typhimurium Hf. Plasmids introduced by transformation ranged in size from 4.4 to 23.2 kb and correlated with resistance to penicillin G, ampicillin, carbenicillin, cephalothin, cefoperazone, cefamandole, mezlocillin, piperacillin, and in some cases, tetracycline and kanamycin. DNA-DNA hybridization experiments localized these resistance genes to a highly duplicated 6.3-kb fragment of the total EcoRI restriction digest of the S. typhimurium Hf plasmid pool.     

Preliminary characterization of a food-borne multiple-antibiotic-resistant Salmonella typhimurium strain.

Plasmid characterization studies were conducted on a Salmonella typhimurium strain isolated from pasteurized milk and from a symptomatic patient during the 1985 Illinois salmonellosis outbreak. This strain (Hf) was reported to possess an unusual plasmid profile which distinguished it from all Salmonella strains isolated in the United States prior to 1984. Antibiotic susceptibility testing revealed that the strain was resistant to tetracycline, erythromycin, clindamycin, sulfisoxazole, sulfadiazene, triple sulfa, cefoperazone, streptomycin, mezlocillin, piperacillin, carbenicillin, penicillin, ampicillin, and kanamycin. Plasmid analysis revealed that the strain possessed four plasmids with sizes of approximately 158, 98, 10.2, and 6.0 kilobase pairs (kb). Successive transfer at 43 degrees C led to increased antibiotic sensitivity in 75.5% of the isolates screened. Electroporation and calcium chloride treatment were each used to transform plasmid-free Escherichia coli strains with the plasmid pool from S. typhimurium Hf. Plasmids introduced by transformation ranged in size from 4.4 to 23.2 kb and correlated with resistance to penicillin G, ampicillin, carbenicillin, cephalothin, cefoperazone, cefamandole, mezlocillin, piperacillin, and in some cases, tetracycline and kanamycin. DNA-DNA hybridization experiments localized these resistance genes to a highly duplicated 6.3-kb fragment of the total EcoRI restriction digest of the S. typhimurium Hf plasmid pool.     

Study of E. coli penicillin amidase. The pH dependence of the equilibrium constant of ampicillin enzymatic hydrolysis]

The equilibrium parameters of the hydrolysis of ampicillin catalysed by penicillin amidase were determined within the pH range of 4.5 to 5.5. The values of the ionization constants of the carboxy group of D-(-)-ALPHA-AMINOPHENYLACETIC ACID (PK1=1.80) and amino group of 6-aminopenicillanic acid (pK2=4.60) were estimated and pH-dependence of the effective free energy of ampicillin hydrolysis was calculated. It was shown that the thermodynamic optimum of ampicillin synthesis was at 3.20 (the value of the effective free energy under the experimental conditions was 3.27 kcal/mole). The value of the "true", pH-independent free energy of hydrolysis (deltasigma) of the amide bond in the ampicillin molecule was determined to be equal to 9.72 kcal/mole. The thermodynamic parameters of ampicillin and benzylpenicillin hydrolysis were compared. The amino group in the alpha-position of phenylacetic acid was shown to have a significant effect on the values of "true" free energy of hydrolysis of the penicillin amide bond and free ionization energy in the system.     

Prospective Study of Ampicillin Rash

A multicentre prospective study of 933 patients being treated with ampicillin showed a rash incidence of 7·3%. The rash was commonest in women and patients suffering from viral infections. Most rashes were maculopapular and were not associated with features of true penicillin allergy. We conclude that the development of a maculopapular rash during or after treatment with ampicillin is not in itself a contraindication to future treatment with the penicillins.     

Antibiotic susceptibility of clinically relevant anaerobes in Estonia from 1999 to 2001

At present little or no data is available regarding the resistance profiles of anaerobic bacteria in relation to the general usage of antibiotics. The objective of this study was to assess whether any potential relationship exists between the dynamics of antibiotic resistance of anaerobic bacteria and the consumption of antibiotics during the last 3 years within the Estonian population. In total, 416 anaerobic isolates were investigated from various clinical samples. The anaerobes were isolated on Wilkins-Chalgren Agar, incubated in an anaerobic glove box and identified by standard methods. beta-lactamase negative strains were tested against metronidazole, clindamycin, benzylpenicillin and the positive strains were further tested against metronidazole, clindamycin, and ampicillin/sulbactam by E-tests. The results of the susceptibility tests were interpreted according to the current criteria of NCCLS. Data from the Estonian State Agency of Medicines was used to assess the antibiotic consumption rate in the population (Defined Daily Doses per 1000 inhabitants annually). The following species of anaerobes were isolated: B. fragilis group, Bacteroides sp., Fusobacterium sp., Porphyromonas sp., Prevotella sp., Peptostreptococcus sp., in addition to various unidentified Gram-positive rods. Metronidazole resistance was not found among Gram-negative bacteria despite a relatively high consumption of this antimicrobial agent in Estonia. Only ampicillin/sulbactam demonstrated excellent in vitro activity against all anaerobes. Unexpectedly despite a relatively low rate of consumption of clindamycin a high rate of resistance to this agent occurred; a similar situation was noted for penicillin. In the present study we did not observe a relationship between the changes in antibiotic consumption (DDD/1000) rate and the resistance pattern of anaerobic bacteria to metronidazole, clindamycin, penicillin and ampicillin/sulbactam during a 3-year follow-up period. High resistance to penicillin among some species and also to clindamycin is similar to the global trend and argues for limited use of these antibiotics in empirical treatment. We would suggest that monitoring of local susceptibility pattern is necessary for the selection of initial empirical therapy.     

Interaction of neomycin with other antibiotics on selected bacterial strains

Antimicrobial combinations are used most frequently to provide broad-spectrum empirical coverage in the treatment of bacterial infections. However, combination of two antibiotics may not influence their activity, may lead to synergy or antagonism in the activity. Neomycin may be combined with one of the following antibiotics: ampicillin, procaine penicillin, gramicidin, bacitracin, polymyxin B, lincomycin, oxytetracycline, and erythromycin in some human and veterinary multiantibiotic drugs distributed in Poland. The checkerboard method has been one of the traditional assays for the measurement of antibiotic interactions. The aim of this study was to analyse the activity interaction of neomycin with second antibiotic in multiantibiotic drugs distributed in Poland on standards and clinical bacterial strains. Checkerboard results for all strains demonstrated synergism for 2.5% of combinations, only for standards strains. In one case Salmonella Enteritidis, in combination of neomycin with bacitracin, inhibition effect was observed. Additive effects were predominant--49%. In 18% neutral effects were shown, but in 26% of combinations FIC indexes were not possible to calculate, because of the resistance of clinical strains to the highest concentration of at least one antibiotic. In combination of aminoglycoside (neomycin) with beta-lactams antibiotics (ampicillin, procaine penicillin) in vitro, no synergy was observed for all examined strains. The best results were achieved for combinations of neomycin with peptide antibiotics (polymyxin, gramicidin and bacitracin)--5 for all 6 synergy effect observed.     

Synergistic Antibacterial Activity of Ampicillin-Cloxacillin Mixtures Against Proteus morganii

Synergistic antibacterial effects of mixtures of ampicillin and cloxacillin and induced penicillinases were investigated in 48 strains of Proteus. The serial tube dilution method was used to determine the minimal inhibitory concentration of ampicillin, cloxacillin, and 2:1 and 1:1 mixtures of ampicillin and cloxacillin. Production of penicillinases was determined by the cellulose acetate membrane method, with ampicillin, cloxacillin, mixtures of ampicillin and cloxacillin, penicillin G, and cephalothin as inducing agents and as substrates for penicillinase. Synergism occurred against P. morganii, but against no other species. The 1:1 ampicillin-cloxacillin combination was synergistic against 13 of 17 P. morganii strains; the 2:1 combination was synergistic against only 9 strains. Penicillinases, demonstrated in all species except P. mirabilis, hydrolyzed penicillin G and cephalothin. Although only P. vulgaris hydrolyzed ampicillin, no species of Proteus hydrolyzed cloxacillin or the ampicillin-cloxacillin mixtures. Penicillinases were, however, induced by ampicillin, cloxacillin, and the mixtures. There was no relationship between production of penicillinase and synergism with mixtures of ampicillin and cloxacillin.     

Efficacy of penicillin therapy of meningococcal infection in children undergoing different regimes of pathogenetic therapy

The course of meningococcal infection and nonspecific and specific immunity in children subjected to different regimens of pathogenetic therapy were studied. It was shown that the clinico-immunological indices were more favourable in children treated with lasix as a diuretic agent. Recovery with defects was observed in 6.8 per cent of the children of this group, while in patients subjected to routine treatment the respective value amounted to 14.6 per cent. The use of lasix in combination with penicillin increased the efficacy of penicillin therapy and shortened the recovery period by 8.4 +/- 0.2 days as compared to that of routine treatment. No unfavourable effect of elevated penicillin concentrations on the lysozyme activity, blood bactericidal characteristics and composition of immunoglobulins A, M and G in the children was recorded.     

Effect of organic solvents on penicillin acylase-catalyzed reactions: interaction of organic solvents with enzymes

The effects of various organic solvents on penicillin acylase-catalyzed synthesis of β-lactam antibiotics (pivampicillin and ampicillin) have been investigated in water-solvent mixtures. The rates of penicillin acylase-catalyzed reactions were found to be significantly reduced by the presence of a small amount of organic solvent. In particular, the rate of enzyme catalysis was extremely low in the presence of ring-structured solvents and acids while enzyme activities were fully restored after removing the solvents. This indicates that interactions between the solvents and the enzyme are specific and reversible. To correlate the inhibitory effects of organic solvents with solvent properties the influence of solvent hydrophobicities and solvent activity on the rate of pivampicillin synthesis was examined. The reaction rate was found to decrease with increasing solvent hydrophobicities, and a better correlation was observed between the reaction rate and solvent activity. The effects of ionic strength on the synthesis of pivampicillin and ampicillin were also examined. The ionic strength dependence indicates that electrostatic interactions are involved in the binding of ionic compounds to the enzyme. On the basis of the active site structure of penicillin acylase, a possible mechanism for molecular interactions between the enzyme and organic solvents is suggested.     

Ampicillin Dosage and Use of Prednisolone in Treatment of Pneumonia: Co-operative Controlled Trial

A controlled trial was carried out to investigate whether the rate of recovery from pneumonia treated with ampicillin is dose related. Sixty-three patients received 1 g ampicillin daily and 63 received 2 g ampicillin daily for seven or 14 days depending on the rate of response. Twenty patients in each of these groups received, in addition, 20 mg prednisolone daily for seven days. The treatment groups were comparable and the results of treatment were similar in the four groups. The only difference which was of statistical significance was that a larger proportion of patients receiving 1 g ampicillin daily became afebrile within one week. All the ampicillin rashes occurred in the patients receiving 2 g ampicillin daily with and without prednisolone. Ampicillin 1 g daily appears to be adequate dosage in the treatment of pneumonia, and the rate of recovery has not been shown to be accelerated by using 2 g. No deleterious effects were noted with additional prednisolone therapy and this appeared to increase the rate at which the patients became afebrile, although the figures were not statistically significant.     

Analysis of biochemical reactions in equilibrium: hydrolysis of penicillin and ampicillin

A general equilibrium model for a class of biochemical reactions was formulated, using the formalism of binding polynomials for the evaluations of the various species. Thermodynamic equilibrium constant was obtained from the observed equilibrium total concentrations of reactants at specified pH and certain ligand concentrations. Results for the hydrolysis of penicillin and ampicillin were analyzed with this equilibrium model. Predicted fractions of hydrolysis products at various pH values were calculated.     

In vitro antibiotic susceptibility of bacteria isolated from EUS-affected fishes in India

AIMS: Twelve antibiotics were evaluated for in vitro sensitivity against 16 bacterial strains isolated from surface lesions of fishes affected with epizootic ulcerative syndrome (EUS). METHODS AND RESULTS: Disc diffusion assay in Mueller-Hinton agar showed that the pseudomonads and aeromonads were mainly resistant to penicillin, ampicillin and erythromycin. Additionally, some were resistant to gentamycin and amoxycillin. However, resistance towards antibiotics previously recommended for EUS treatment, such as oxytetracycline and chloramphenicol, was not observed. Four aeromonads and two pseudomonads were found to induce ulcers when injected intramuscularly in healthy Anabas testudineus. CONCLUSIONS: All six pathogenic isolates were sensitive towards oxytetracycline, chloramphenicol and nalidixic acid. Oxytetracycline seems to be an effective antibiotic, and further investigations to determine the mode of treatment and dose appear to be worthwhile.     

Determination of Antibiotic Susceptibility of Rickettsia by the Plaque Assay Technique

Plaque formation by various rickettsiae was completely inhibited by commercial antibiotic discs impregnated with tetracycline, chloramphenicol, nitrofurantoin, and erythromycin; partial inhibition was observed around discs containing nalidixic acid and sulfisoxazole, but no inhibition was seen around discs containing cephalothin, ampicillin, oxacillin, kanamycin, polymyxin B, streptomycin, or penicillin.