Granulomatous-lymphocytic interstitial lung disease and recurrent sinopulmonary infections in a patient with Good's syndrome.

Good's syndrome is a rare primary immunodeficiency associated with adult thymoma. Complications are mainly autoimmune manifestations and recurrent infections with encapsulated bacteria. Only one possible case of combined granulomatous-lymphocytic interstitial lung disease (GL-ILD) and Good's syndrome have been described earlier, but the patient died at the time of diagnosis. This is the first case of GL-ILD in Good's syndrome with a successful outcome. We present a case of a 43-year-old man with GL-ILD, who suffered from recurrent infections of Haemophilus influenzae and Pneumocystis jirovecii, with 8-year follow-up. After a thymectomy, he was diagnosed with Good's syndrome and GL-ILD. He was treated with prophylactic pivampicillin, quinolones and cephalosporins for his recurrent P. jirovecii and H. influenzae infections, an approach that proved unsuccessful due to resistance, with relapse after cessation. He was stabilised with oral diaminodiphenyl-sulfone for P. jirovecii and colistimethate-sodium inhalations for H. influenzae, which is a new approach to prophylactic treatment.

Penicillins vs trimethoprim-based regimens for acute bacterial exacerbations of chronic bronchitis: meta-analysis of randomized controlled trials.

OBJECTIVE: To compare the effectiveness and toxicity of semisynthetic penicillins (SSPs) (amoxicillin, ampicillin, pivampicillin) and trimethoprim-based regimens (trimethoprim, trimethoprim-sulfamethoxazole, trimethoprim-sulfadiazine) in treating acute bacterial exacerbations of chronic bronchitis (ABECB). DATA SOURCES: We searched MEDLINE, EMBASE, Current Contents, and the Cochrane Central Register of Controlled Trials to identify and extract data from relevant randomized controlled trials (RCTs). STUDY SELECTION: Only RCTs comparing penicillins with trimethoprim-based regimens for the treatment of patients with ABECB that reported data on effectiveness, toxicity, or mortality were considered eligible for this meta-analysis. SYNTHESIS: Out of 134 RCTs identified in the search, 5 RCTs involving 287 patients were included in the analysis. There were no differences between patients with ABECB treated with SSPs and those treated with trimethoprim, alone or in combination with a sulfonamide, in treatment success (intention-to-treat patients: n = 262, odds ratio [OR] 1.68, 95% confidence interval [CI] 0.91-3.09; clinically evaluable patients: n = 246, OR 1.59, 95% CI 0.79-3.20) or number of drug-related adverse events in general (n = 186 patients, OR 0.37, 95% CI 0.11-1.24), frequency of diarrhea or skin rashes, or number of withdrawals due to adverse events (n = 179 patients, OR 0.27, 95% CI 0.07-1.03). CONCLUSION: Based on limited evidence leading to wide CIs of the estimated treatment effects, SSPs and trimethoprim-based regimens seem to be equivalent in terms of effectiveness and toxicity for ABECB.

Azithromycin versus pivampicillin in the treatment of acute exacerbations of chronic bronchitis: a single-blind, double-dummy, multicentre study.

This single-blind, double-dummy, multicentre study compared oral azithromycin, administered as tablets, 500 mg once daily for 3 days, versus oral pivampicillin, 700 mg twice daily for 10 days, in adults with acute exacerbations of chronic bronchitis (not needing parenteral antibiotic therapy, hospitalization or oxygen support). Clinical success (cure + improvement) rates were similar for both groups at the end of treatment (day 10; azithromycin, 124 of 133 [93%]; pivampicillin, 79 of 92 [86%]) and at follow-up (day 52; 98 of 126 [78%] versus 66 of 81 [81%]). The treatments produced similar levels of pathogen eradication at the end of treatment (49 of 54 [91%] versus 32 of 37 [86%]). Azithromycin-treated patients had significantly reduced chest discomfort at the end of treatment, and a trend towards improved lung function. The two groups were similar with respect to improvements in other clinical symptoms and patient well-being, and to the incidences of adverse events and treatment discontinuations. This oral azithromycin regime is an effective treatment for acute exacerbations of chronic bronchitis, similar in efficacy to the longer pivampicillin regime and may offer superior patient compliance.

A follow-up study of birth outcome in users of pivampicillin during pregnancy.

BACKGROUND: Pivampicillin is a prodrug which is widely used in Scandinavian countries for oral antibiotic therapy. The pivaloyl moiety has a carnitine depleting effect, which has caused doubts about the safety of administering pivampicillin during pregnancy. The aim of the study was to evaluate the risk of congenital malformations in general, preterm delivery and low birth weight in users of pivampicillin. METHODS: Seven hundred and ninety-one women who had redeemed a prescription of pivampicillin during their first pregnancy from 1 January 1991 to 31 December 1996 were identified in the North Jutland Pharmaco-Epidemiological Prescription Database. By linkage to the Danish Medical Birth Registry and Regional Hospital Discharge Registry we compared their birth outcomes (malformations, preterm delivery and low birth weight) with the outcomes in 7472 reference pregnancies on which the mother had not redeemed any prescription at all during pregnancy. RESULTS: The prevalence of malformations was 5.5% (11 cases) in offspring of 199 women who had used pivampicillin during the first trimester, and 5.6% (420 cases) in offspring of controls (OR: 0.95, 95% CI: 0.51-1.76). Furthermore, we did not find any significant risk of preterm delivery (OR: 0.75, 95% CI: 0.54-1.05) or low birth weight (OR: 0.93, 95% CI: 0.55-1.57). CONCLUSION: This study showed no increased risk of congenital malformations, preterm delivery or low birth weight in offspring of women who had redeemed a prescription for pivampicillin during pregnancy.

[Ciprofloxacin and pivampicillin in acute epididymitis in men above the age of 40 years]. / Ciprofloxacin og pivampicillin ved epididymitis acuta hos maend over 40 år.

Ciprofloxacin 500 mg orally twice daily was compared to pivampicillin 700 mg orally twice daily for 10 days in 172 men (41-85 years) with acute epididymitis. Failure of treatment occurred in 48 patients, in 15/76 (19.7%) receiving ciprofloxacin versus in 33/82 (40.2%) receiving pivampicillin (p = 0.006). Ciprofloxacin 500 mg orally twice daily is more effective than pivampicillin 700 mg orally twice daily and has fewer adverse events.

Randomised trial of pivampicillin plus pivmecillinam vs. pivampicillin in children and young adults with chronic obstructive pulmonary disease and infection with Haemophilus influenzae.

A prospective, randomised, single-blind comparative trial was carried out to determine whether double beta-lactam treatment with pivampicillin plus pivmecillinam is more effective than pivampicillin alone in the treatment of recurrent and chronic lung infections with Haemophilus influenzae in patients with chronic obstructive pulmonary disease (COPD) or cystic fibrosis (CF). Fifty-six children and young adults with COPD or CF were randomised to the clinical study. The patients were allocated at random to receive perorally either pivmecillinam, 40 mg/kg/day, combined with pivampicillin, 50 mg/kg/day, or pivampicillin 50 mg/kg/day alone for 14 days. A cross-over pharmacokinetic study using the same drugs was carried out in 10 CF patients to determine the antibiotic concentrations in serum and sputum after a single dose of each drug. The clinical study showed no significant differences in clinical scoring, lung function tests or adverse events after treatment with pivampicillin plus pivmecillinam or pivampicillin alone. Follow-up microbiological evaluation 2 and 6 weeks after the end of treatment showed that the offending pathogen was eradicated in 68% of the patients treated with pivampicillin plus pivmecillinam and in 67% of the patients treated with pivampicillin alone. Reinfection with another biotype was more common in the combination group (50% vs. 21%) than in the pivampicillin group. In the pharmacokinetic study the median peak serum concentration occurred two hours after intake of tablets. The efficacy of double beta lactam treatment in lung infections with H. influenzae appears to be equivalent to that of ampicillin on clinical lung symptoms, lung function tests, adverse effects and bacteriology.

Infectious temporomandibular joint disease in the horse: computed tomographic diagnosis and treatment of two cases.

Diagnostic imaging and treatment of unilateral destructive temporomandibular joint disease in two horses is described and discussed. Computed tomography appeared to be the best imaging technique for these lesions. The disease can be followed by functional recovery after the infection has resolved.

Clinical efficacy of ampicillin, pivampicillin and procaine penicillin G in a soft tissue infection model in ponies.

Tissue chambers, implanted subcutaneously in ponies, were inoculated with Streptococcus zooepidemicus. The animals received either no antibiotics or one of the following treatments: pivampicillin per os (19.9 mg/kg, equivalent to 15 mg/kg ampicillin, every 12 h) for 7 or 21 days (7 and 5 ponies, respectively), procaine penicillin G intramuscularly (12 mg/kg = 12,000 IU/kg, every 24 h) for 7 days (7 ponies), or ampicillin sodium intravenously (equivalent to 15 mg/ kg ampicillin, every 8 h) for 1 day (5 ponies). Only intravenous administration was started before infection (prophylactically), the other treatments were started 20 h after infection (curatively). A total of 7 ponies received no antibiotics. In untreated controls, the infection led to abscessation of the tissue chamber in 4 to 10 days. Curative treatment with either pivampicillin or procaine penicillin G for 7 days resulted in a reduction of viable bacteria in the tissue chamber but did not eliminate the infection, resulting in abscessation in 5 to 14 days. However, administration of pivampicillin for 21 days eliminated the streptococci in five out of five ponies and prophylactic administration of ampicillin was successful in three out of five ponies.

Relationship of carnitine and carnitine precursors lysine, epsilon-N-trimethyllysine, and gamma-butyrobetaine in drug-induced carnitine depletion.

Plasma concentrations and rates of urinary excretion of carnitine and some of its precursors were studied in three groups of children receiving drugs known to cause carnitine depletion. Patients in group A received pivampicillin and a molar equivalent of carnitine for 7 d. Patients in group B received pivampicillin with a 5.8-fold molar excess of carnitine for 1 wk. Patients in group C were treated chronically with valproic acid and received a molar equivalent (to valproic acid) of carnitine for 14 d. Patients in group A had markedly increased (16-fold) urinary carnitine ester excretion concomitant with diminished urinary free carnitine and gamma-butyrobetaine output and lower plasma free carnitine concentration. Supplementation with one molar equivalent of carnitine (to pivampicillin) was ineffective in preventing the reduction of plasma carnitine concentration observed with pivampicillin treatment alone. For group B patients, administration of excess carnitine resulted in a further increase (35-fold) of urinary carnitine ester output with no decrease of plasma carnitine concentration, urinary gamma-butyrobetaine, or free carnitine excretion. For patients in group C, the initially low plasma free and total carnitine concentrations and urinary output of carnitine and carnitine esters markedly increased with carnitine supplementation, but urinary excretion of gamma-butyrobetaine remained unchanged. The plasma concentrations and urinary output of L-lysine and epsilon-N-trimethyllysine remained unchanged within each group before and after treatment. A positive linear correlation was found between urinary epsilon-N-trimethyllysine and 3-methylhistidine output, indicating that the rate of epsilon-N-trimethyllysine excretion correlates with the amount of 3-methylhistidine liberated by protein turnover.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of bacterial vaginosis with metronidazole or pivampicillin.

In a double-blind randomized controlled trial from general practice, we assessed the efficacy of treatment with either metronidazole or pivampicillin in patients fulfilling the diagnostic criteria of bacterial vaginosis. 50 women were treated with metronidazole 500 mg twice daily and 54 with pivampicillin 700 mg twice daily, both for seven days. Evaluated four weeks after the start of treatment, we found a significantly higher cure rate in the metronidazole group (90%) than in the pivampicillin group (69%) (p = 0.01). Cure was defined as lack of fulfillment of the diagnostic criteria of bacterial vaginosis. Test for confounding according to parity and complaint of vaginal discharge showed no influence. Side-effects were significantly commoner in the pivampicillin group (28%) than in the metronidazole group (8%). We consider that metronidazole is a potent drug in the treatment of bacterial vaginosis, with pivampicillin as a useful alternative.

Group B streptococcal chorioamnionitis and neonatal septicemia following 8 days pivampicillin and metronidazol prophylaxis after premature rupture of membranes; a case report.

A case of preterm premature rupture of the membranes (PPROM) in the 31st week of gestation is reported. Initial cultures from the cervix and urine were without pathogenic microorganisms. After 8 days of prophylactic pivampicillin and metronidazol, culture from the cervix showed profuse growth of Group B Streptococci (GBS) and the patient developed symptoms of chorioamnionitis. Cesarean section was performed and the infant presented GBS-septicemia. In spite of continued treatment with pivampicillin, culture from the cervix on day 6 post partum still showed profuse growth of GBS. Prolonged prophylactic per oral administration of broad-spectrum antibiotics after PPROM may not always protect against infectious complications. Literature is reviewed, and it is discussed whether the applied regimen in some cases even may favour the occurrence of serious infections.

Efficacy of the combination pivampicillin/pivmecillinam compared to placebo in the treatment of convalescent carriers of nontyphi Salmonella.

In a randomized, double blind, placebo-controlled study 36 patients aged 16-77 years who had been carriers of nontyphi Salmonella species for 10-21 weeks were given the combination pivampicillin/pivmecillinam or placebo for four weeks in order to eradicate the carrier state. 34/36 patients who fulfilled the criteria for inclusion in the study were evaluable for efficacy, 16 in the pivampicillin/pivmecillinam group and 18 in the placebo group. Seven patients in the pivampicillin/pivmecillinam group had to terminate the treatment after 10-25 days because of adverse reactions, mainly exanthema and nausea. After therapy 8/16 patients treated with pivampicillin/pivmecillinam and 4/18 patients treated with placebo had negative stool cultures for Salmonella species during a mean follow-up time of 13 and 20 weeks, respectively. No abnormalities could be found in those patients who did not respond to therapy except for earlier cholecystectomy in two patients, both in the pivampicillin/pivmecillinam group.

Pivampicillin/pivmecillinam in the treatment of shigella carriers.

24 patients (4-65 years old; median age 29 years) excreting shigella bacteria greater than 8 weeks were treated with the combination pivampicillin (0.25 g)/pivmecillinam (0.20 g), 2 tablets 3 times a day for 14 days. 23/24 patients (96%) were culture negative after treatment. The one patient that did not respond to treatment carried a strain with intermediate sensitivity to mecillinam and resistance to ampicillin. It is concluded that pivampicillin/pivmecillinam is effective for patients excreting shigella bacteria.

Pivampicillin versus doxycycline in the treatment of chlamydial urethritis in men.

Pivampicillin and doxycycline were compared in the treatment of chlamydial urethritis in 80 heterosexual men. The trial was carried out in a double-blind, comparative parallel group fashion. Forty patients were treated with 700 mg of pivampicillin twice daily and another 40 with 200 mg of doxycycline on the first day and thereafter with 100 mg of doxycycline and one placebo tablet daily. Both treatments lasted for 9 days. Follow-up examinations were carried out 2 weeks (14-16 days) and 4 weeks (26-30 days) after the start of treatment. Altogether five (12.5%) of the forty pivampicillin-treated patients were clinical failures and three (7.5%) still harbored Chlamydia trachomatis after treatment. The corresponding figures for the doxycycline-treated patients were two (5.1%) and one (2.6%). The difference between the treatment results of the two groups did not reach statistical significance.

Pivmecillinam in long-term prophylaxis to girls with recurrent urinary tract infection.

Pivmecillinam in a single bed-time dose of 5-10 mg/kg was given as long-term prophylaxis to 20 girls with recurrent bacteriuria for a total of 228 months. Symptomatic recurrences occurred in 4 girls, i.e. 1.8 infections/100 months as compared to 17/100 months during the year preceding the study. The frequency of positive urine cultures during prophylaxis was 11%. 10 of the 15 isolates were enterococci, resistant to mecillinam. In rectal swabs examined for the presence of aerobic gram-negative bacteria, enterobacteria were isolated in 78% with a low rate of resistance to mecillinam (11%). Thus pivmecillinam offered effective protection against recurrent urinary tract infections, and did not tend to select resistant enterobacteria in the bowel, but allowed resistant enterococci to cause a few symptomatic infections.

A clinical comparative study of ofloxacin and pivampicillin in acute exacerbations of chronic bronchitis.

A controlled clinical study employing a double-blind, double-dummy technique was carried out on 84 patients with purulent exacerbations of chronic bronchitis. Ofloxacin (200 mg x 2 daily) and pivampicillin (700 mg x 3 daily), were compared for efficacy, safety, and adverse reactions. Both regimens had high bacteriological elimination rates (94.1, 97.2%) and clinical cure rates (97.4, 97.6%). However, there were fewer adverse reactions and a greater patient acceptance in the ofloxacin treated group.