Endocarditis neumocócica: revisión a propósito de un caso y nueva pauta de tratamiento asociada a fosfomicina / Pneumococcal endocarditis: report of a case involving a novel treatment with association of fosfomycin and a review of the literature

Se presenta un interesante caso de endocarditis bacteriana en un varón de 12 años de edad, que asociaba como patología de base una comunicación interventricular membranosa, que presentó buena respuesta al tratamiento asociado con penicilina en altas dosis, gentamicina y fosfomicina. Se adjunta una revisión bibliográfica acerca de los distintos tratamientos antibióticos descritos, incluidas las pautas menos habituales. Se incluye en la discusión una extensa explicación de la asociación al tratamiento antibiótico de fosfomicina

The authors present an interesting case of bacterial endocarditis in a 12 year-old boy, the underlying cause of which was a membranous ventricular septal defect. The infection responded well to treatment with high-dose penicillin, in combination with gentamycin and fosfomycin. A review of the literature dealing with the different types of antibiotic therapy, including less conventional approaches, is provided, and the reasons for administering combination treatment involving fosfomycin are explained in detail

Fosfomicina trometamol. Dosis múltiples como pauta larga en el tratamiento de las infecciones urinarias bajas / Fosfomycin trometamol: Multiple-dose regimen for the treatment of lower urinary tract infections

Introducción. El tratamiento de las infecciones urinarias del tracto inferior no complicadas se realiza con pautas de tratamiento cortas. En otras circunstancias no está tan clara la pauta que hay que seguir. Cuando la infección urinaria del tracto inferior no se produce en una mujer joven, la recomendación terapéutica es la utilización de antibióticos durante al menos 7 días, y son las quinolonas y el cotrimoxazol los antibióticos utilizados con mayor frecuencia. Pero debido al porcentaje de resistencias de los microorganismos implicados en este tipo de infecciones, es aconsejable evaluar otras pautas de tratamiento, de forma que habría que evaluar, entre otros, el uso de antibióticos con un menor índice de resistencias como fosfomicina trometamol, en períodos de tratamiento más largos que el uso tan extendido en dosis única. Métodos. Desde los datos de eliminación urinaria de fosfomicina obtenidos en voluntarios sanos en un estudio previo, se han simulado las concentraciones de este antibiótico en orina tras la administración de 2 dosis. Se ha calculado el intervalo más idóneo para mantener concentraciones urinarias por encima del punto de corte de Escherichia coli para fosfomicina (16 mg/l), uno de los microorganismos implicados con mayor frecuencia en este tipo de infecciones. Resultados. Las concentraciones de fosfomicina en orina se mantienen por encima del punto de corte durante 161 h cuando se administran 2 dosis de 3 g de fosfomicina trometamol separadas 72 h. Éste supone un tiempo de eficacia del 96% en un período total de 7 días. Conclusión. La pauta teórica, desde el punto de vista farmacocinético, para conseguir concentraciones de fosfomicina en orina por encima del punto de corte de E. coli es la administración de 2 dosis de 3 g de fosfomicina trometamol separadas 72 h (AU)

Introduction. A short antibiotic regimen is recommended for the treatment of uncomplicated lower urinary tract infection. Nevertheless, the treatment to follow in other situations is not so clearly defined. When the person affected by lower urinary tract infection is not a young woman, it is recommended to treat at least 7 days, and quinolones or cotrimoxazole are the antibiotics most often used. However, because of the frequency of drug resistance in this type if infection, it is advisable to apply antibiotics with lower rates of resistance, such as fosfomycin trometamol, for longer treatment periods than the often-used single dose. Methods. Using the data on urinary elimination of fosfomycin after a single dose obtained in a prior study in healthy volunteers, we simulated the urinary concentrations of this antibiotic following administration of two doses. In addition, we calculated the interval of administration required to achieve urinary concentrations greater than 16 mg/L, the critical concentration of sensitivity for Escherichia coli, one of the most commonly implicated microorganisms in these infections. Results. Fosfomycin concentrations in urine persisted above the defined cut-off for 161 hours after administration of two 3-g doses of fosfomycin trometamol, 72 hours apart. This implied an efficacy time of 66% in a period of 7 days. Conclusion. From the pharmacokinetic viewpoint, the optimum dosage of fosfomycin trometamol to achieve appropriate urinary concentrations along 7 days is administration of two 3-g doses, 72 hours apart (AU)

Renal hypersensitivity vasculitis associated with dapsone.

We describe clinical and pathological features of kidney and skin involvement in a patient with hypersensitivity vasculitis associated with dapsone. Although visceral damage occurs rarely, similar skin and kidney histopathologic and immunohistochemical findings indicate that this organ is a target for type IV cell-mediated dapsone reaction. To our knowledge, this is the first reported case of renal hypersensitivity vasculitis associated with dapsone.

[The use of aminopenicillin combined with a beta-lactamase inhibitor in outpatients of oral surgery and dentistry]. / Béta-laktamáz-gátlóval kombinált amino-penicillin alkalmazása az ambuláns szájsebészeti és fogászati gyakorlatban.

On the basis of the information gained from the literature the amoxicillin/clavulanic acid combination has attained the leading position in dentistry and outpatient oral surgery practices as regards the order of application of antibiotics. The explanation for this may be that in 60-70% of the cases of odontogenic inflammation, besides the pathogenic anaerobic bacteria there is an increasing necessity to eliminate beta-lactamase-producing bacteria as well. The authors applied the amoxicillin/clavulanic acid combination (Aktil Duo 625 mg) to support the--primarily surgical--treatment of 14 oral and dental surgery conditions on a total of 60 patients. After analysing the results and side effects they came to the conclusion that the application of the mentioned combination was very successful in dentistry and outpatient oral surgery practices.

Is a long-term ranitidine-based triple therapy against Helicobacter pylori only a heritage of the past? A prospective, randomized clinicopharmacological study.

BACKGROUND: Acid suppression plus two antibiotics is currently considered the gold standard anti-Helicobacter pylori treatment, but the effective role of gastric antisecretory drugs is still poorly understood. AIMS: To compare a 14-day ranitidine-based triple regimen against Helicobacter pylori with one based on omeprazole, and to study the influence of antisecretory drugs on metronidazole pharmacokinetics in human plasma. METHODS: A total of 150 dyspeptic H. pylori-infected patients were randomized for ranitidine 300 mg b.d. (RCM group) or omeprazole 20 mg b.d. (OCM group) 14-day triple therapy, with clarithromycin 500 mg b.d. and metronidazole 500 mg b.d. On the eighth day of therapy, metronidazole pharmacokinetics was studied in plasma by high-performance liquid chromatography. The pharmacokinetic parameters (terminal half-life, area under the curve, peak-plasma level, peak time) of metronidazole were computed using standard non-compartmental methods. H. pylori status was monitored before and 4 weeks after the end of therapy by histology, serology and rapid urease test. RESULTS: On an intention-to-treat basis, eradication rates were 91 and 76% for the RCM and OCM groups respectively (P < 0.02). Significantly different pharmacokinetic parameters of metronidazole were found between the groups: peak-plasma level (P < 0.01) and area under the curve (P < 0.02). CONCLUSION: Our results show that the RCM regimen was more effective than that based on OCM and that the antisecretory drugs affected metronidazole availability, increasing the efficacy of ranitidine-based regimens.

[Reactive arthritis due to Clostridium difficile]. / Arthrite réactionnelle a Clostridium difficile.

Extracolonic manifestations of Clostridium difficile infections have rarely been reported as a cause of reactive arthritis. We report the case of a monoarticular arthritis following pseudomembranous colitis. A 45 year-old man was admitted for fever and monoarthritis of the left knee, 8 days after the onset of a C. difficile enterocolitis associated with urethritis. Samples obtained from the knee, urine, and blood cultures remained sterile. Bone scintigraphy revealed a left knee and forefoot hyperfixations. The association of arthritis and urethritis led us to the diagnosis of Fiessinger-Leroy-Reiter syndrome. Antibiotics for arthritis were ineffective and stopped, but they were continued for colitis. NSAIDs were prescribed and clinical manifestations disappeared within 24 hours, the patient resumed walking after 48 hours. Four months later there was no relapse and no sequela.

[A travel abroad-associated case of Legionella pneumonia diagnosed by urinary antigen detection test].

A 75 year-old male was admitted to our hospital with high fever and dyspnea. He had traveled in Turkey 10 days before. His chest X-ray showed infiltrations in bilateral lower lung fields. His urinary antigen detection test for Legionella pneumophilia was positive. He was treated with pazufloxacin added to clarithromycin and his symptons were promptly resolved.

Pancreatitis due to codeine.

Pancreatitis is a rare adverse effect of codeine. We report the case of a 42-year-old man who suffered from epigastric pain 1 hour after taking a tablet containing amoxicillin plus clavulanic acid (500/125 mg) and another tablet containing acetaminophen plus codeine (500/30 mg) for a respiratory infection. He was admitted to the emergency room and was treated with metamizol and pantoprazole. A few minutes after receiving intravenous doses of both drugs he developed a maculopapular and itching eruption with facial angioedema. Laboratory tests showed high levels of serum amylase, GOT, GPT and total bilirubin. Serological tests for several viruses showed no evidence of recent infection. Ultrasonography was negative for biliary lithiasis and showed only cholecystectomy performed in 2000. The patient was sent to our department where skin prick and oral challenge tests were performed with negative results. For ethical reasons, oral challenge with codeine was not carried out. We believe that our patient had codeine-induced pancreatitis. The most likely underlying pathophysiological mechanism was probably codeine-induced spasm of the sphincter of Oddi combined with sphincter of Oddi dysfunction related to a previous cholecystectomy. Allergy departments should be aware of possible non-immunological adverse.

High rate of Helicobacter pylori eradication with sequential therapy in elderly patients with peptic ulcer: a prospective controlled study.

BACKGROUND: Helicobacter pylori eradication rates with triple therapies are decreasing, and few data in elderly patients are available. A 10-day sequential regimen succeeded in curing such H. pylori infection in unselected patients. AIM: To compare this sequential regimen and the standard triple therapy for H. pylori eradication in geriatric patients with peptic ulcer. METHODS: Overall, 179 H. pylori-infected patients with peptic ulcer were enrolled (mean age: 69.5 years; range: 65-83). Patients were randomized to 10-day sequential therapy (rabeprazole 20 mg b.d. plus amoxicillin 1 g b.d. for the first 5 days, followed by rabeprazole 20 mg, clarithromycin 500 mg and tinidazole 500 mg, all b.d., for the remaining 5 days) or standard 7-day triple regimen (rabeprazole 20 mg, clarithromycin 500 mg and amoxicillin 1 g, all b.d.). Helicobacter pylori status was assessed by histology and rapid urease test at baseline and 4-6 weeks after completion of treatment. RESULTS: The sequential regimen achieved eradication rates significantly higher in comparison with the standard regimen at both intention-to-treat (94% vs. 80%; P = 0.008) and per-protocol (97% vs. 83%; P = 0.006) analyses. In both treatment groups, compliance to the therapy was high (> 95%), and the rate of mild side-effects was similarly low (< 12%). At repeated upper endoscopy, peptic ulcer lesions were healed in 97% patients, without a statistically significant difference between the sequential regimen and the standard triple therapy. CONCLUSIONS: In elderly patients with peptic ulcer disease, the 10-day sequential treatment regimen achieved significantly higher eradication rates in comparison with standard triple therapy.

In vitro selection of resistance in Pseudomonas aeruginosa and Acinetobacter spp. by levofloxacin and ciprofloxacin alone and in combination with beta-lactams and amikacin.

OBJECTIVES: The aim of this study was to evaluate the ability of levofloxacin and ciprofloxacin alone and in combination with either ceftazidime, cefepime, imipenem, piperacillin-tazobactam or amikacin to select for antibiotic-resistant mutants of Pseudomonas aeruginosa and Acinetobacter spp. METHODS: Clinical strains of P. aeruginosa (n = 5) and Acinetobacter spp. (n = 5) susceptible to all the drugs used in the study were assayed. Development of resistance was determined by multi-step and single-step methodologies. For multi-step studies, MICs were determined after five serial passages on antibiotic-gradient plates containing each antibiotic alone or in combination with levofloxacin or ciprofloxacin. Acquisition of resistance was defined as an increase of >or=4-fold from the starting MIC. In single-step studies, the frequency of spontaneous mutations was calculated after a passage on plates containing antibiotics alone and in combinations at concentrations equal to the highest NCCLS breakpoints. RESULTS: Serial passages on medium containing single antibiotics resulted in increased MICs for each antibiotic; MIC increases were limited by antibiotics in combination. A decrease in the number of strains with MICs above the NCCLS breakpoints occurred when fluoroquinolones were combined with a second antibiotic for both P. aeruginosa and Acinetobacter spp. isolates. Frequencies of mutation were higher for antibiotics alone than for combinations. CONCLUSIONS: Use of combinations of fluoroquinolones with beta-lactams and amikacin reduces the risk for in vitro selection of resistant P. aeruginosa and Acinetobacter spp.

A 10-day levofloxacin-based triple therapy in patients who have failed two eradication courses.

BACKGROUND: A standard third-line treatment is lacking, and European guidelines recommend performing culture in these patients. However, the use of this procedure as 'routine practice' is definitively not feasible. AIM: To evaluate the eradication rate of a 10-day levofloxacin-based triple therapy in patients who have failed two eradication courses for Helicobacter pylori. METHODS: A total of 151 patients with persistent Helicobacter pylori infection after two treatments were studied. Patients were considered positive if two of three endoscopic tests were positive. Susceptibility testing was also performed. Patients received a standard dose of proton-pump inhibitors twice daily, levofloxacin 250 mg twice daily and amoxicillin 1 g twice daily, for 10 days. Endoscopic follow-up was carried out 4-6 weeks after the end of eradication therapy. RESULTS: About 76% (95% CI: 68.8-82.3), and 85% (95% CI: 77.5-89.7) of patients were eradicated according to intention-to-treat and per-protocol analysis, respectively. Eradication rates of the strains showed as 92% (95% CI: 83.2-96.7) of those resistant to both metronidazole and clarithromycin but susceptible to levofloxacin. CONCLUSIONS: In patients who failed previous regimens, the 10-day levofloxacin-based triple therapy is safe and effective, allowing eradication in almost 80% of the patients.

Once daily clarithromycin extended-release vs twice-daily amoxicillin/clavulanate in patients with acute bacterial sinusitis: a randomized, investigator-blinded study.

OBJECTIVE: To compare the efficacy and tolerability of clarithromycin extended-release (ER) to amoxicillin/ clavulanate in patients diagnosed with acute bacterial sinusitis. RESEARCH DESIGN AND METHODS: In a controlled, multicenter, investigator-blinded study, 437 ambulatory patients at least 12 years old with signs/symptoms and radiographic findings of acute sinusitis were randomized to receive clarithromycin ER 1000 mg once daily or amoxicillin/ clavulanate 875 mg/l25 mg twice daily for 14 days. MAIN OUTCOME MEASURES: Clinical and bacteriological response rates were determined at a test-of-cure visit, which was conducted up to 10 days following the completion of treatment. Radiological response was assessed at a follow-up visit. RESULTS: The clinical cure rate in clinically evaluable patients was 98% (184/188) in the clarithromycin ER group and 97% (179/185) in the amoxicillin/clavulanate group (95% CI for the difference in rates [-2.4%, 4.7%]). Clinical cure was sustained at the follow-up visit (96% for each treatment group). The pathogen eradication rates were 94% (61/65) in the clarithromycin ER group and 98% (61/62) in the amoxicillin/clavulanate group (95% CI for difference in rates [-12.0%, 2.9%]). The radiological success rate was 94% (172/183) in both the clarithromycin ER and amoxicillin/clavulanate groups (95% CI for difference in rates [-4.9%, 4.9%]). Symptomatic improvement or relief was observed as early as 2 days-5 days after the initiation of study drug, with a statistically significantly higher resolution rate of sinus pressure (p = 0.027) and improvement/resolution rate of nasal congestion (p = 0.035) during treatment with clarithromycin ER. The resolution/improvement rate at the test-of-cure visit for each treatment group was > or = 94% for the primary acute sinusitis signs/symptoms, with a statistically significantly higher resolution/improvement rate of purulent nasal discharge with clarithromycin ER (p = 0.010). Both study drugs had a positive and rapid impact on quality of life. Patients reported a high level of satisfaction and probability of using either study antibiotic again, and health care resource use was low, with slightly fewer sinusitis-related physician and outpatient visits required by patients in the clarithromycin ER group (p = 0.055). The treatment groups were comparable with respect to incidence of drug-related adverse events. CONCLUSION: In this multinational population of patients with acute bacterial sinusitis, clarithromycin ER was comparable, and for selected measures superior, to amoxicillin/clavulanate based on clinical, bacteriological, and radiological responses as well as quality of life measures, satisfaction with antibiotic therapy, and health care resource utilization.

[A case of successful medical treatment for necrotizing fasciitis of the chest wall with diabetic nephropathy].

A 52-year-old man was given a diagnosis of type 2 diabetes mellitus at age 39. At age 46, he stopped taking medication. Two weeks after burning his legs at low temperature, he fell, using his right arm to protect his legs. The next day, he complained of pain and slight swelling from his right shoulder to his anterior chest and came to our hospital. At that time, a plain computed tomography scan suggested gasogenic bacterial infection and we discussed the indications for debridment. Although his widespread inflammation required extensive treatment including thoracostomy, we abandoned surgical treatment and administered several antibiotics in appropriate combination because of his severe condition. After admission, the mass grew rapidly and it was diagnosed as necrotizing fasciitis based on percutaneous needle biopsy and clinical findings. Although both inflammatory reactions and mass size tended to improve, he had repeated recurrence of pain and swelling in his right anterior chest. When he had a second recurrence, he received additional short-term steroid therapy. Afterwards he had no further recurrence. In this case, early clinical diagnosis, using broad-spectrum antibiotics prior to definite diagnosis, and additional short-term steroid therapy at the time of the recurrence were effective.

Systematic review and meta-analysis: is 1-week proton pump inhibitor-based triple therapy sufficient to heal peptic ulcer?

AIMS: To systematically review the efficacy on ulcer healing of 1-week combination of a proton pump inhibitor plus two antibiotics and to perform a meta-analysis of randomized clinical trials to evaluate whether 7 days of proton pump inhibitor-based triple therapy is sufficient to heal peptic ulcer. METHODS: Studies where 1-week proton pump inhibitor-based triple therapy was administered to heal peptic ulcer were included. Randomized clinical trials comparing the efficacy on ulcer healing of 7-day proton pump inhibitor-based triple therapy versus this same regimen but prolonging the proton pump inhibitor for several more weeks were included in the meta-analysis. Electronic and manual bibliographical searches were conducted. Meta-analysis was performed combining the odds ratios of the individual studies. RESULTS: Twenty-four studies (2342 patients) assessed ulcer healing with 1-week proton pump inhibitor-based triple therapy. Mean healing rate was 86%, and 95% in Helicobacter pylori-eradicated patients. Six studies (862 patients), were included in the meta-analysis. Mean ulcer healing rate with a 7-day treatment was 91% versus 92% when proton pump inhibitor was prolonged for 2-4 more weeks (odds ratio = 1.11; 95% confidence interval = 0.71-1.74). CONCLUSION: In patients with peptic ulcer and H. pylori infection, prolonging therapy with proton pump inhibitor after a triple therapy for 7 days with a proton pump inhibitor and two antibiotics is not necessary to induce ulcer healing.

Acute otitis media: making sense of recent guidelines on antimicrobial treatment.

High-dose amoxicillin (80 to 90 mg/kg/d divided twice daily) remains the drug of choice for treatment of acute otitis media despite increasing antimicrobial resistance. For persistent or recurrent acute otitis media, guidelines recommend high-dose amoxicillin/clavulanate (90/6.4 mg/kg/d), cefdinir, cefprozil, cefpodoxime, cefuroxime, or ceftriaxone. Increasing the dose of amoxicillin does not cover infection with beta-lactamase-producing pathogens; add the beta-lactamase inhibitor clavulanate to amoxicillin, or choose a cephalosporin with good activity against S pneumoniae and good beta-lactamase stability. Key factors for enhancing compliance are taste of suspension, dosing frequency, and duration of therapy.

Single versus combination intravenous antibiotic therapy for people with cystic fibrosis.

BACKGROUND: Choice of antibiotic, and the use of single or combined therapy are controversial areas in the treatment of respiratory infection in cystic fibrosis (CF). Advantages of combination therapy include wider range of modes of action, possible synergy and reduction of resistant organisms; advantages of monotherapy include lower cost, ease of administration and reduction of drug-related toxicity. Current evidence does not provide a clear answer and the use of intravenous antibiotic therapy in CF requires further evaluation. OBJECTIVES: To assess the effectiveness of single compared to combination intravenous antibiotic therapy for treating people with CF. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Most recent search of the Group's register: January 2004. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing a single intravenous antibiotic with a combination of that antibiotic plus a second antibiotic in people with CF. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. MAIN RESULTS: Twenty-seven trials were identified, of which eight trials (with 356 participants) comparing a single agent to a combination of the same antibiotic and one other, were included. There was a wide variation in the individual antibiotics used in each trial. In total, the trials included seven comparisons of a beta-lactam antibiotic (penicillin-related or third generation cephalosporin) with a beta-lactam-aminoglycoside combination and three comparisons of an aminoglycoside with a beta-lactam-aminoglycoside combination. These two groups of trials were analysed as separate subgroups. There was considerable heterogeneity amongst these trials, leading to difficulties in performing the review and interpreting the results. The meta-analysis did not demonstrate any significant differences between monotherapy and combination therapy, in terms of lung function; symptom scores; adverse effects; and bacteriological outcome measures. These results should be interpreted cautiously. Six of the included trials were published between 1977 and 1988; these were single centre trials with flaws in the randomisation process and small sample size. Overall, the methodological quality was poor. AUTHORS' CONCLUSIONS: The results of this review are inconclusive. The review raises important methodological issues. There is a need for an RCT which needs to be well designed in terms of adequate randomisation allocation, blinding, power and long-term follow up. Results need to be standardised to a consistent method of reporting, in order to validate the pooling of results from multiple trials.