Comparison of cyclacillin and amoxicillin for therapy for acute maxillary sinusitis.

Cyclacillin, a new aminosalicylic semisynthetic penicillin, was compared with amoxicillin for the therapy of acute bacterial maxillary sinusitis in 80 patients (ages, 12 to 70 years) in a prospective, double-blind, randomized clinical trial. Direct sinus aspirations for quantitative culture were done for all patients before and after 10 days of therapy. Both drugs were administered at a dosage of 500 mg orally three times daily. Among culture-positive patients, clinical cure was achieved in 23 of 26 patients and 25 of 27 patients treated with cyclacillin and amoxicillin, respectively, for an overall cure rate of 91%. Bacteriologic failure occurred in 9% (4 of 44 patients); 3 of the 4 failures were in the cyclacillin group. There was no correlation between clinical or bacteriologic cure and the results of sinus transillumination (clear, dark) at follow-up. Initial direct sinus aspirates were positive in 57 of 80 cases (70%): 25 (44%) of these were the result of Streptococcus pneumoniae and 23 (40%) were the result of Haemophilus influenzae. All of these isolates were susceptible (MIC, less than or equal to 0.5 microgram/ml) to both study drugs; no ampicillin-resistant H. influenzae was recovered. On day 10 of therapy, mean concentrations of both drugs in serum were 2.5 to 2.7 micrograms/ml, but no antibiotic was detectable in 20 of 21 simultaneous sinus aspirates. Adverse effects (rash, diarrhea) were infrequent and similar in both groups. Cyclacillin appears equivalent to amoxicillin in the therapy of acute maxillary sinusitis.

Single-dose therapy for cystitis in women. A comparison of trimethoprim-sulfamethoxazole, amoxicillin, and cyclacillin.

We evaluated single-dose regimens of trimethoprim-sulfamethoxazole, amoxicillin, and cyclacillin as treatment for acute cystitis in 38 women. The trial was prematurely stopped because of frequent treatment failures. At two days after treatment, all 13 patients given trimethoprim-sulfamethoxazole were cured, while four (31%) of 13 given amoxicillin and four (33%) of 12 given cyclacillin had persistent bacteriuria. At two weeks, 11 (85%) of 13 patients given trimethoprim-sulfamethoxazole, six (50%) of 12 given amoxicillin, and three (30%) of ten given cyclacillin were cured. One patient with positive results of antibody-coated bacteria testing who was treated with cyclacillin had signs and symptoms of acute pyelonephritis three days after treatment, and two patients treated with amoxicillin and one treated with trimethoprim-sulfamethoxazole converted antibody-coated bacteria test results from negative to positive after therapy. We conclude that single-dose treatment of cystitis in unselected women with cyclacillin and amoxicillin may result in low cure rates and that progression to acute pyelonephritis may occur following ineffective single-dose therapy.

Haemophilus influenzae infections. The impact of resistance on the use of aminopenicillins and other antimicrobials in outpatient therapy.

The clinical manifestations of Haemophilus influenzae infections and the growing problem of ampicillin-resistant strains are reviewed. Despite the fact that approximately 25 percent of H. influenzae are resistant to penicillin and ampicillin, oral aminopenicillins (ampicillin, amoxicillin, bacampicillin, and cyclacillin) are commonly used for the outpatient management of these infections. The characteristics of these drugs and the rationale for their use are discussed and compared with alternative approaches to therapy. This subject requires periodic review in consideration of the increasing prevalence of ampicillin and multiple antibiotic resistance among H. influenzae isolates.

Cyclacillin versus amoxicillin as treatment for acute otitis media.

A double-blind study of 240 pediatric outpatients with acute otitis media demonstrated that cyclacillin, administered three times a day for ten days, is as effective as and better tolerated than a similar regimen of amoxicillin. Clinical success was achieved in 96% of the children treated with each drug, and the bacteriologic cure rate was 98% in each treatment group. Only three of the 119 children (2.5%) treated with cyclacillin had drug-related diarrhea, in contrast to 17/121 children (14%) treated with amoxicillin (P less than .01). This greater tolerance for cyclacillin may be due to its more effective and rapid absorption in the upper gastrointestinal tract. The results are discussed in terms of the low incidence of resistant strains of Haemophilus influenzae and the advantages of cyclacillin as the first-line treatment for acute otitis media.

Cyclacillin in the treatment of acute sinus infections and exacerbations of chronic infections.

Cyclacillin was used to treat 40 patients with bacterial sinus infections, either acute or exacerbations of chronic infections. The drug was administered orally in a dosage of 500 mg every six hours for ten days, although three patients required extended treatment. More than 70% of the patients had remission of symptoms in six days, and all but the aforementioned three had remission in ten days or less. More than 90% of the patients had a moderate to good response; only two patients had a poor response. The only side effects were gastrointestinal disorders, which disappeared with administration of antacids. No side effects were noted in 72.5% of patients. Cyclacillin proved to be an effective and well-tolerated antibiotic for infections of the paranasal cavities.

Multicenter comparison of cyclacillin and amoxicillin in the treatment of acute streptococcal pharyngitis.

A double-blind study of 134 pediatric outpatients with acute streptococcal pharyngitis demonstrated that cyclacillin, administered three times a day for ten days, is as effective as a similar regimen of amoxicillin. Clinical success was achieved in 95% of the children treated with either drug. A bacteriological cure was seen in 82% of the children evaluated in the cyclacillin group and 90% of those evaluated in the amoxicillin group. The mean time required for remission of signs and symptoms in the respective treatment groups was 3.1 and 3.0 days. Only two patients (3%) in each treatment group experienced an adverse effect of the prescribed drug.

Double-blind multicenter comparison of cyclacillin and amoxicillin for the treatment of acute otitis media.

A multicenter double-blind study of 363 pediatric outpatients with acute otitis media demonstrated that cyclacillin, administered in three divided doses (three times a day) for ten days, is as effective as and better tolerated than a similar regimen of amoxicillin. The bacteriologic cure rate for patients with middle-ear cultures was 98% in both treatment groups. Remission of signs and symptoms was significantly faster in the cyclacillin group (3.1 days) than in the amoxicillin group (4.3 days) (P less than 0.05). Of the 179 children treated with cyclacillin, three (1.7%) had drug-related diarrhea in contrast to 18 of the 184 (9.8%) children treated with amoxicillin (P less than 0.01). Cyclacillin produces a rapid resolution of symptoms and a low incidence of diarrhea.

Pharmacological and in vitro evaluation of cyclacillin: assessment as potential single-dose therapy for treatment of Neisseria gonorrhoeae infection.

The pharmacokinetic properties of cyclacillin administered as a 3.0-g oral dose, with and without progenecid, have been studied and correlated with in vitro activity of the drug against 109 isolates of Neisseria gonorrhoeae. By 8 h after dosage, levels of cyclacillin in serum declined below the minimal inhibitory concentration and the inferior antibacterial activity of cyclacillin (compared with that of amipicillin) suggest that cyclacillin is not a promising alternative to ampicillin for single-dose treatment of gonorrhea.

[Comparative experimental study of cyclacillin and ampicillin]. / Sravnitel'noe izuchenie tsiklatsillina i ampitsillina v éksperimente.

Cyclacillin was compared with ampicillin by its bacteriostatic efficiency in vitro, chemotherapeutic efficiency in experimental infections of mice and rats and pharmacokinetic characteristics. It was found that cyclacillin was not superior to ampicillin by its antibacterial action. By a number of characteristics it was even significantly inferior. The pharmacokinetic advantages of cyclacillin were not considered significant.

Double-blind clinical trials of oral cyclacillin and ampicillin.

A double-blind study was performed to compare the clinical response and the incidence of side effects in 2,581 patients administered ampicillin or cyclacillin for infections of the genitourinary or respiratory tract, infections of the skin and soft tissues, or for otitis media. There was no significant difference in clinical response and bacterial eradication. All side effects, including diarrhea and skin rash, were approximately twice as frequent in patients treated with ampicillin.

Cyclacillin: microbiological and pharmacological properties and use in chemotherapy of infection - a critical appraisal.

The pharmacological and microbiological properties of cyclacillin were discussed and its usefulness in the management of a variety of infections was reviewed. The antibacterial spectrum and clinical utility of this agent generally parallels that of ampicillin, but there are minor differences in specificity with regard to individual microorganisms. The in vitro activity of cyclacillin against gram-negative pathogens varies greatly, the results fluctuating in accordance with the composition of the assay medium of method. The drug has demonstrated excellent therapeutic effectiveness against experimental infections produced by both gram-positive and gram-negative pathogens, thus making questionable a prediction of therapeutic effectiveness from in vitro susceptibility tests alone. Cyclacillin is more resistant to beta-lactamase hydrolysis than ampicillin, is much better absorbed when given by mouth and, as a result, the levels reached in the blood and in the urine are considerably higher than those obtained with the same dose of ampicillin. Cyclacillin produces fewer and milder side-effects than ampicillin.

Comparative studies of the activity of ciclacillin and dicloxacillin.

The penicillins ciclacillin and dicloxacillin demonstrate marked similarities in biological activity but, as far as can be determined, differ substantially in respect to the degree of protein binding, which is relatively low for ciclacillin and relatively high for dicloxacillin. In mice infected with Staphylococcus aureus Smith, ciclacillin is considerably more active than dicloxacillin, although both drugs are similarly effective in vitro and similarly absorbed and eliminated in vivo. The high degree of protein binding exhibited by dicloxacillin could therefore very probably explain its relatively low chemotherapeutic activity. Moreover, the in vitro and in vivo findings of the study are inconsistent with the tenets of the tau/2 thesis.

Relationship between the chemotherapeutic effectiveness of ciclacillin and ampicillin and the time of their administration in experimental infections.

In an attempt to explain the discrepancy between the weak in vitro activity and good clinical efficacy of ciclacillin, a time-dosage-efficacy study was made in order to investigate the relationship of the effectiveness of this antibiotic to the interval between experimental infection and administration in comparison to ampicillin, which because of its similar antimicrobial spectrum and completely different pharmacokinetic properties was particularly suitable for use in the study. Various single oral doses of both antibiotics were administered once to NMRI (SPF) mice at various intervals (0, 1, 2 or 3 h) following experimental infection with E. coli WT 102, E. coli 3033 or E. coli 026:B6 and the CD50's determined and compared statistically. It was demonstrated that the chemotherapeutic effectiveness of both antibiotics was markedly dependent on the interval between experimental infection and administration. Whereas ampicillin was superior to ciclacillin when drug and infective organism were administered simultaneously (0 h), ciclacillin was superior to ampicillin when it was administered 3 h after experimental infection. Both antibiotics were about equally effective when administered 1 or 2 h after infection. The difference in the serum concentrations and rates of absorption and excretion of the two drugs is assumed to be the reason for this phenomenon, and the pharmacokinetic characteristics of ciclacillin, in particular its rapid and almost complete absorption and rapid attainment of high peak serum levels, are discussed as at least a partial explanation of the difference in its in vitro and in vivo activities.

[Ciclacillin therapy for diseases of the urinary tract]. / Ciclacillin-Therapie bei Harnwegserkrankungen

In our own controlled bacteriological investigations, ciclacillin showed a good effect in urological infections at a daily dosage of 3 g for 10 days. The efficacy is comparable to that of ampicillin and corresponds to that of the double blind trials bescribed in the literature. The specially good tolerance is worthy of note.