Attainment of Target Antibiotic Levels by Oral Treatment of Left-Sided Infective Endocarditis: A POET Substudy.

BACKGROUND: In the POET (Partial Oral Endocarditis Treatment) trial, oral step-down therapy was noninferior to full-length intravenous antibiotic administration. The aim of the present study was to perform pharmacokinetic/pharmacodynamic analyses for oral treatments of infective endocarditis to assess the probabilities of target attainment (PTAs). METHODS: Plasma concentrations of oral antibiotics were measured at day 1 and 5. Minimal inhibitory concentrations (MICs) were determined for the bacteria causing infective endocarditis (streptococci, staphylococci, or enterococci). Pharmacokinetic/pharmacodynamic targets were predefined according to literature using time above MIC or the ratio of area under the curve to MIC. Population pharmacokinetic modeling and pharmacokinetic/pharmacodynamic analyses were done for amoxicillin, dicloxacillin, linezolid, moxifloxacin, and rifampicin, and PTAs were calculated. RESULTS: A total of 236 patients participated in this POET substudy. For amoxicillin and linezolid, the PTAs were 88%-100%. For moxifloxacin and rifampicin, the PTAs were 71%-100%. Using a clinical breakpoint for staphylococci, the PTAs for dicloxacillin were 9%-17%.Seventy-four patients at day 1 and 65 patients at day 5 had available pharmacokinetic and MIC data for 2 oral antibiotics. Of those, 13 patients at day 1 and 14 patients at day 5 did only reach the target for 1 antibiotic. One patient did not reach target for any of the 2 antibiotics. CONCLUSIONS: For the individual orally administered antibiotic, the majority reached the target level. Patients with sub-target levels were compensated by the administration of 2 different antibiotics. The findings support the efficacy of oral step-down antibiotic treatment in patients with infective endocarditis.

Combination of thioridazine and dicloxacillin as a possible treatment strategy of staphylococci.

We have previously shown that the phenothiazine, thioridazine, acts in synergy with the beta-lactam antibiotic, dicloxacillin, to kill methicillin-resistant Staphylococcus aureus. In this study, we investigated whether synergy by combining these two drugs could also be observed in vancomycin intermediate susceptible S. aureus (VISA) and methicillin-resistant Staphylococcus epidermidis (MRSE). Synergy was observed in three of four tested VISA strains, suggesting that the thickening of cell wall does not interfere with the effects of thioridazine. In S. epidermidis, no synergy was observed in all tested strains, suggesting that synergy by combining thioridazine and dicloxacillin is isolated to S. aureus species.

Cheilitis glandularis in an African-American woman: response to antibiotic therapy.

A 52-year-old black woman presented with a 2-day history of lower lip swelling 5 days after starting a new medication, lisinopril. She had never experienced similar episodes in the past. She denied shortness of breath, tightening of the throat, swelling of the tongue, generalized cutaneous eruption, urticaria, or pruritus. She also denied symptoms consistent with facial paresis. Her past medical history was significant for hepatitis C infection, coronary artery disease, and hypertriglyceridemia. She had a 15 pack-year smoking history and denied both alcohol and drug abuse. She had never received a blood transfusion and was HIV negative. Physical examination disclosed a tender, swollen, and erythematous lower lip with induration, oozing, and crusting (Figure 1). Pinpoint openings evident throughout the lip surface exuded a clear, sticky, mucoid secretion. Tongue, parotid glands, and regional lymph nodes were normal. The working diagnosis was angioedema secondary to lisinopril. The presumptive offending drug was discontinued, and conservative therapy (topical clobetasol ointment, oral ranitidine, and oral fexofenadine) was initiated. Despite treatment, signs and symptoms persisted unabated. One week after initial presentation, a punch biopsy of her lower lip was taken to rule out granulomatous cheilitis and sarcoidosis. Histopathology included diffuse lymphohistiocytic infiltrate, minimal microabscess formation, and notable absence of granulomata. There was neither hypertrophy nor detectable abnormality of the salivary glands, with the exception of infiltrating mononuclear cells. Based on the clinical history and compatible pathologic findings, a diagnosis of cheilitis glandularis was made. Specifically, crusting and erosion clinically suggested a diagnosis of the superficial suppurative subtype of cheilitis glandularis. The patient received oral penicillin (dicloxacillin, 1.0 g/d) combined with oral fluoroquinolone (ciprofloxacin, 1.0 g/d). Within 2 weeks of starting the antibiotics, the lip swelling significantly decreased (Figure 2) and the patient was left with a mildly indurated nodule at the labial commissure. Following a 4-week course of continued antibiotic treatment, the lip returned to near baseline state. At both 6-month and 1-year follow-up visits, the lip remained normal.

Treatment and outcome of Staphylococcus aureus bacteremia: a prospective study of 278 cases.

BACKGROUND: Staphylococcus aureus bacteremia is still a serious problem, and the optimal treatment is under debate. Only a few studies concerning treatment are available. METHODS: The study population was all patients with a positive blood culture result for S aureus in Copenhagen County, Denmark, from May 1994 through April 1996. Of 278 patients with S aureus bacteremia, 186 were evaluated according to outcome in a prospective, observational follow-up study. The time above the minimum inhibitory concentration was estimated for dicloxacillin sodium for each treatment regimen and evaluated by logistic regression along with other potential risk factors. RESULTS: The following variables were statistically associated with death: the presence of an uneradicated focus (odds ratio [OR], 6.7; 95% confidence interval [CI], 2.1-21.0); the presence of septic shock (OR, 3.7; 95% CI, 1.5-9.1); the total daily dose of penicillinase-stable penicillin less than 4 g (OR, 3.7; 95% CI, 1.3-11.1); and age 60 years or older (OR, 2.4; 95% CI, 1.1-5.3). The following variables were significantly associated with recurrence: the total daily dose of penicillinase-stable penicillin less than 3 g (OR, 3.9; 95% CI, 1.6-10.0) and the presence of a secondary focus (OR, 3.2; 95% CI, 1.3-7.7). Among 155 patients with observation time longer than duration of treatment, this factor (duration of treatment, <14 days) was significantly related to mortality (OR, 0.84; 95% CI, 0.76-0.94). CONCLUSIONS: Focus eradication and the dosing of penicillinase-stable penicillin are important to the outcome of S aureus bacteremia. We recommend treatment with at least 1 g of penicillinase-stable penicillins 4 times daily for longer than 14 days.

Etiología de sepsis neonatal y sensibilidad a los antibióticos en el Nuevo Hospital Civil de Guadalajara / Ethiology of neonatal sepsis and sensitivity to antibiotics in the New Civil Hospital of Guadalajara

Objetivo: Identificar las bacterias causantes de sepsis neonatal y sus patrones de sensibilidad a diversos antibióticos en el Nuevo Hospital Civil de Guadalajara. Material y métodos: El estudio se realizó en la unidad de cuidados intensivos neonatales de un hospital de segundo nivel de atención en guadalajara, Jalisco, México. Se analizaron 74 neonatos con sospecha clínica y/o paraclínica de sepsis, bajo un diseño prospectivo, transversal, observacional y comparativo. Se consideró como infectados a los neonatos que en dos hemocultivos tomados de sitios diferentes de venopunción, tuvieron el mismo aislamiento. Los antibiogramas se realizaron por el método de kirby-Bauer, con los puntos recomendados por la NCCLS. Resultados: Hubo 41 (55.4 por ciento) pacientes con hemocultivos positivos. De los aislamientos, 30 (73 por ciento) correspondieron a K. pneumoniae y 8 (19 por ciento) a S. epidermidis. Todas las cepas de K. pneumoniae fueron resistentes a ampicilina, pero 93 por ciento fueron sensibles a los aminoglucósidos y las cefalosporinas de tercera generación probados. Todas las cepas de estafilococos fueron sensibles a vancomicina y sólo dos fueron resistentes a dicloxacilina. Conclusiones: El 98 por ciento de las cepas de K. pneumoniae presentó el mismo patrón de sensibilidad a los antibióticos, lo que sugiere una transmisión horizontal intrahospitalaria. La gran mayoría de los aislamientos fueron sensibles a los antimicrobianos de uso común, por lo que sugerimos que el tratamiento empírico inicial debe incluir a aminoglucósidos como gentamicina o amikacina, asociados a dicloxacilina o en casos específicos vancomicina y dejar como alternativa el uso de cefalosporinas de tercera generación.

Clinical experiences with fusidic acid in cystic fibrosis patients.

A survey of Staphylococcus aureus lung infection in 243 patients with cystic fibrosis (CF) was conducted between 1986 and 1988. A total of 217 patients (89%) received 1605 courses of anti-staphylococcal therapy given during this period. The majority of courses comprised combined therapy with two anti-staphylococcal drugs. The combination of dicloxacillin and fusidic acid was employed most frequently. Some patients were given other anti-staphylococcal regimens, because of penicillin allergy (14 cases) or dyspeptic side effects with fusidic acid (21 patients). A small but significant increase in precipitins against S. aureus was observed during the study period. Bacterial resistance to the anti-staphylococcal drugs used remained at a low level (strains resistant to methicillin less than 0.1%, strains resistant to fusidic acid 1.2%). When the isolates were compared with 56,140 strains of S. aureus isolated from non-CF patients hospitalized in Denmark over the same period, no differences in phagetypes or in antibiotic resistance were seen, indicating that selection of strains and cross infection do not seem to be a major problem in CF patients.

Meningoencefalitis purulenta neonatal: bacterias causales y sensibilidad a los antimicrobianos / Neonatal purulent meningoencephalitis: causative bacteria and sensitivity of antimicrobial agents

Con la finalidade de determinar le etiología de la meningoencefalitis purulenta (MEP) neonatal y la sensibilidad de los microorganismos aislados, se revisaron los diversos cultivos del líquido cefalorraquídeo tomado a recién nacidos durante un periodo de cinco años. En total los cultivos fueron 3 101, con un promedio de positividad de 7.6 por ciento, y por pacientes resultó de 5.6 por ciento. Las bacterias gramnegativas representaron las dos terceras partes de los microorganismos encontrados, de las que Pseudomonas ocupó el primer lugar, seguida de E. coli y Kelbsiella; entre los grampositivos predominaron S. epidermidis y S. viridians. Entre los gramnegativos la mejor sensibilidad se observó para amikacina, y la de grampositivos (S. epidermidis y S. aureus) lo fue para la dicloxacilina. Si bien aún predominan las bacterias gramnegativas, llama la atención la aparición de S. epidermidis como agente causal de la MEP, y deben buscarse antecedentes que orienten hacia dicha etiología. La epidemiología referida debe considerarse como local, y no extrapolarse a otras unidades hospitalarias

[Dicloxacillin: its chemotherapeutic action and experimental kinetic characteristics]. / Dikloksatsillin: khimioterapevticheskoe deistvie i osobennosti kineti v éksperimente

Activity against 50 clinical staphylococcal strains, chemotherapeutic efficiency, absorption and distribution of dicloxacillin in animals were studied in comparison with oxacillin. It was found that dicloxacillin was superior to oxacillin with respect to a number of their properties. The antibiotic was characterized by a higher antistaphylococcal activity, especially with respect to methicillin resistant strains. It was more effective in treatment of staphylococcal pneumonia and septicopiemia of albino mice. The drug was better absorpted when used orally and was detected in the blood in therapeutic concentrations for long periods of time. The antibacterial titer of the blood serum after dicloxacillin administration was 4 times higher than that of oxacillin.