Concomitant Antibiotic Therapy Research Articles

Antifungal Treatment with Caspofungin: A Single Centre Experience.

Infections are the main complication for patients with hematologic diseases and severe neutropenia and among them fungal infections are the most diffucult to treat and a major cause of mortality for these patients. Now we have a new antifungal class, Echinocandins which work with a new and different mechanism of action regarding azoles and amphotericin B, so we wanted to verify the tolerability and efficacy of Caspofungin (Caspo). From January 2004 until now we have treated 15 consecutive oncohemopatic and neutropenic patients admitted at our Institution. The schedule of treatment was: in case of persistent fever (at least 4 days) during broad spectrum antibiotic therapy a high-resolution CT-scan of the lungs, an abdomen US-scan, swabs from pharynx, nose and rectum and blood cultures were performed. In case of positivity of one or more of these findings suggesting for invasive fungal disease, Caspofungin was administered at the dosage of 70 mg i.v. on the first day and 50 mg i.v. from the second day; the infusion time was 1 hour. The patients were 10 males and 5 females, the mean age was 46 yrs (range 19–60 yrs). The diagnoses were: acute myeloid leukemia 8, acute lymphoblastic leukemia 3, lymphoma 4; the disease's phases were: onset 3, first remission 3, remission>I 2, partial remission 5, relapse 1, resistant 1. Two patients received an allogeneic BMT, 1 an autologous BMT, the other patients an induction or consolidation or rescue chemotherapy course. In four cases Caspo was administered as secondary prophylaxis of a previous invasive fungal infection while for the other patients Caspo was administered for persistent fever and at least one lesion of the lungs or other organs with no evidence of bacterial or viral infection. The mean time of treatment was 18 days (range 6–21 days); the treatment was not discontinued for anyone of them because of adverse events; the dosage of Caspo was not changed for anyone. For the 2 allogeneic BMT Cyclosporine A administration was not changed and we did not found any renal or liver alterations. All the patients received a concomitant broad spectrum antibiotic therapy (association of Tazobactam/Piperacilline, Amikacine and Vancomycin) and for none of them we registered any liver or renal disfunction. No adverse events during the infusion of Caspo were seen and it was not necessary to administer any drug before the infusion. We did not seen breakthrough fungal infections. In 2 patients a proven fungal infection (Aspergillus fumigatus and Aspergillus spp) was demonstrated so the other cases remained probable or possible infections. No progression of the infection was seen. All the infections, except one, resolved; one patient died after 6 days of antifungal treatment for leukemia progression. Five patients died: 4 for leukemia and 1 for bacterial infection (Pseudomonas aeruginosa) after the fungal infection. In conclusion now we have a new treatment option for fungal infections in neutropenic patients and this option is safe, it does not preclude any other treatment (such as CsA), it is well tolerated and the resolution rate of the infections is very high, probably because of the new mechanism of action of the drug. Moreover the cost of the drug is lower than other antifungal treatments. According to these preliminary data we have decided to continue this experience to verify them in a larger cohort of patients.

Papillon‐Lefèvre Syndrome: A Successful Outcome

Papillon-Lefèvre syndrome (PLS) is a rare autosomal recessive condition manifested clinically by hyperkeratosis of the palms and soles and rapidly progressive periodontitis resulting in loss of deciduous and permanent teeth. This case report describes the clinical periodontal findings and treatment of a 10-year-old male patient with PLS. The patient provided informed consent, and the study was conducted in accordance with the Helsinki Declaration of 1975, as revised in 2000. Upon initial presentation, a full periodontal examination was completed. Conventional probing depths, clinical attachment levels (CAL), gingival index (GI), and plaque index (PI) were measured prior to initial therapy, which involved oral hygiene instruction and scaling and root planing. At reevaluation, initial treatment proved unsuccessful, and a surgical approach with concomitant systemic antibiotic therapy was implemented. In addition, the patient's dermatologist treated his palmoplantar keratoderma with systemic retinoids. Subsequently, the patient was placed on a strict 3-month maintenance protocol and was evaluated over a period of 1 year. Initial treatment with mechanical therapy, oral hygiene instruction, frequent recalls, and systemic antibiotics did not yield efficacious results. However, with the addition of surgical treatment, a favorable clinical outcome was obtained. Numerous treatment regimens for the periodontal disease seen in PLS can be found in the literature. We demonstrate successful treatment of the periodontal disease seen in this condition using mechanical therapy, systemic antibiotics, and surgical modalities; over a period of 1 year, we were able to achieve significant reductions in gingival inflammation and erythema.

The combination of ACTH-cortisone-hydrocortisone with antibiotics in the management of overwhelmingly severe infections

Jahn et al describe the salutary effects of “hormone therapy” in 82 patients with severe infection. Their clinical experience from 1950 to 1953 is summarized and includes presenting patient signs and symptoms, hospital treatment, and eventual outcome. Though not specifically stated, the mortality rate for their patients was 33%, quite similar to mortality rates observed today. More than 50% of their patients were children, many of whom had either Neisseria meningitidis or Haemophilus influenza infections. They write, “There is no question but that the administration of ACTH or cortisone in sufficient amounts to patients with severe infections will result in rapid and striking clinical improvement.” The authors suggest possible mechanisms for these beneficial effects and provide a guideline for steroid use. They specifically mention that all patients with meningococcal meningitis should receive hormonal therapy. Furthermore, they recommend the use of steroid treatment with concomitant antibiotic therapy and adjuvant measures including diet, potassium, testosterone, and estrogen. They make specific recommendations that the duration of antibiotic therapy always be greater than that of hormone therapy, lest cortisone induced “alteration of the inflammatory response permit greater proliferation and dissemination of bacteria.” In sum, strong recommendations are made for the adjuvant use of steroids in all patients with severe infections, especially meningococcal disease. They might be surprised to find that 50 years later the debate continues. Over the past 50 years, recommendations for steroid therapy in patients with severe infection have varied widely. In the 1960s and 1970s, high-dose solumedrol (30 mg/kg/dose) was accepted treatment for patients with septic shock.1 Then in 1987, two randomized trials conducted in adults and two subsequent meta-analyses suggested that steroid treatment for septic shock should be “abandoned.”2-5 More recently, Annane et al demonstrated that steroid therapy for adult patients with relative adrenal insufficiency and septic shock can significantly reduce mortality.6 In 2002, a College of Critical Care Medicine published guideline indicated that children with “refractory septic shock be treated with steroids.”7 Despite this recommendation, no efficacy data regarding steroid treatment for children with septic shock exists. As a result, efforts are underway to conduct a randomized, placebo-controlled trial to examine the value of steroid therapy in children with septic shock. Indeed, the pendulum continues to swing in the saga of steroids and infection. Will we have the definitive answer in the next citation for “50 Years Ago in The Journal”? Download .pdf (.02 MB) Help with pdf files Application 1References can be found online at www.us.elsevierhealth.com/jpeds.

The combination of ACTH-cortisone-hydrocortisone with antibiotics in the management of overwhelmingly severe infections*1

Jahn et al describe the salutary effects of “hormone therapy” in 82 patients with severe infection. Their clinical experience from 1950 to 1953 is summarized and includes presenting patient signs and symptoms, hospital treatment, and eventual outcome. Though not specifically stated, the mortality rate for their patients was 33%, quite similar to mortality rates observed today. More than 50% of their patients were children, many of whom had either Neisseria meningitidis or Haemophilus influenza infections. They write, “There is no question but that the administration of ACTH or cortisone in sufficient amounts to patients with severe infections will result in rapid and striking clinical improvement.” The authors suggest possible mechanisms for these beneficial effects and provide a guideline for steroid use. They specifically mention that all patients with meningococcal meningitis should receive hormonal therapy. Furthermore, they recommend the use of steroid treatment with concomitant antibiotic therapy and adjuvant measures including diet, potassium, testosterone, and estrogen. They make specific recommendations that the duration of antibiotic therapy always be greater than that of hormone therapy, lest cortisone induced “alteration of the inflammatory response permit greater proliferation and dissemination of bacteria.” In sum, strong recommendations are made for the adjuvant use of steroids in all patients with severe infections, especially meningococcal disease. They might be surprised to find that 50 years later the debate continues.

The contraceptive vaginal ring, nuvaring, shows no interaction with broad spectrum oral antibiotics

Two studies were performed to investigate whether ethinylestradiol (EE) and etonogestrel (ENG) released from NuvaRing (NR) are affected by concomitant treatment with the antibiotics amoxicillin (A) and doxycycline (D). Sixteen healthy women per study (age: 18 to 40 yrs.) were randomised to 21 days of treatment with NuvaRing, either alone (control) or concomitantly with amoxicillin (875 mg twice daily for 10 days, study I) or doxycycline (100 mg once daily for 10 days, study II). After a 7-days washout they were crossed over to the alternate treatment. Based on serum EE and ENG levels, area under the curve (AUC) values over 12 hours (amoxicillin) or 24 hours (doxycycline) on days 1 and 10 and for the whole of days 1-11 and days 1–22 were calculated and tested for interactions based on FDA guidance. Geometric mean results of the various AUCs (ng.h.mL−1) are presented in the following table. Calculation of EE and ENG interaction/control ratios plus 90% confidence intervals confirmed the absence of PK interactions for both antibiotics. In both studies, NuvaRing with or without concomitant antibiotic therapy was well tolerated. These studies show an absence of PK interactions between NuvaRing and concomitant broad-spectrum antibiotics and indicate that NuvaRing is a reliable contraceptive option even in situations where users may require antibiotic treatment. Clinical Pharmacology & Therapeutics (2004) 75, P33–P33; doi: 10.1016/j.clpt.2003.11.124 Table 1. study I AUCday1 AUCday10 AUCday1–11 AUCday1–22 EE NR 0.32 0.25 5.58 11.1 NR + A 0.32 0.24 5.30 10.9 ENG NR 11.1 24.4 427 950 NR + A 10.2 24.9 427 959 study II AUCday1 AUCday10 AUCday1–11 AUCday1–22 EE NR 0.61 0.51 5.28 10.8 NR + D 0.58 0.48 5.02 10.3 ENG NR 19.9 42.7 363 811 NR + D 21.0 43.1 371 827

Eradication of methicillin-resistant Staphylococcus aureus with an antiseptic soap and nasal mupirocin among colonized patients – an open uncontrolled clinical trial

BackgroundAim of the study was to determine the clinical efficacy of a new antiseptic liquid soap (Stellisept® scrub), based on the combination of undecylenamidopropyltrimonium methosulphate (4%) and phenoxyethanol (2%), for eradication of MRSA among colonized patients who do not receive antibiotic therapy.MethodsOver two years 50 MRSA patients in 6 hospitals were observed. Treatment was defined as the daily application of Stellisept scrub for the antiseptic body and hair wash (at least 60 s) in combination with nasal mupirocin. A treatment cycle was a minimum of 5 days treatment. Screening was carried out at least 48 h after the treatment cycle was finished, with 24 h between each of the requested three or more samplings, which included the nasopharynx, groin, axilla, perineum and other MRSA-positive skin areas.ResultsFifteen cases were retrospectively excluded (lack of outcome documentation, concomitant antibiotic therapy, open wounds). All 35 patients had colonization with MRSA before antiseptic treatment on the skin, in the groin (80%), the axilla (25.7%), the perineum (20%) or other skin areas (14.3%). Colonization at more than one skin sites was found in 34.3%. Nasal colonization was found in 21 of 28 patients (75%), 7 patients were without nasal screening prior to the antiseptic treatment. After one treatment cycle MRSA was eradicated in 25 patients (71.4%), after a second cycle the total eradication rate was 91.4%, after a third cycle the rate increased to 94.2%. No patient discontinued the antiseptic treatment due to dermal intolerance of the product.ConclusionsProgressive eradication of MRSA carriage was observed with the antiseptic soap and mupirocin. The eradication rate was not biased by concomitant antibiotic treatment, screening during treatment or lack of evidence for colonization in contrast to other studies with other preparations.

Current Understanding and Management of Chronic Hepatosplenic Suppurative Brucellosis

To outline the characteristics and define appropriate management of chronic hepatosplenic suppurative brucellosis (CHSB), 905 patients with brucellosis were analyzed. Sixteen episodes of CHSB (14 in the liver and 2 in the spleen) were found in 15 patients. Six patients had had previous remote brucellosis. Twelve patients presented with systemic symptoms, and 12 with local symptoms. Cultures of blood samples yielded negative results in all cases except 1, and the results of cultures of pus specimens were positive for Brucella melitensis in only 2 cases. All patients showed calcium deposits surrounded by a hypodense area on computed tomography. Patients often had low titers of agglutinating antibody. In patients who were receiving conservative management, early response was successful in 50% and late response was successful in 33.3%. In the patients who underwent surgery and concomitant antibiotic therapy, early and late response was successful in 100%. Thus, CHSB mainly represents a local reactivation of previous brucellosis. Its diagnosis may be difficult to establish and surgery may be required to cure many patients.

Immunological infertility among Nigerian men: incidence of circulating antisperm auto‐antibodies and some clinical observations: a preliminary report

To (i) establish the incidence of circulating antisperm auto-antibodies among infertile men; (ii) relate this incidence to the high prevalence of sexually-transmitted diseases (STDs) in sub-Saharan Africa and; (iii) elucidate the effect of steroid and other therapy on semen quality and subsequent fertility of the patients. Serum samples from 50 infertile men and 50 age-matched controls were assayed by two agglutination techniques for anti-sperm antibodies. Mean sperm concentrations were determined before and after steroid treatment of patients having antibody titres of 1:64 or above. Serum levels of follicle-stimulating hormone, luteinizing hormone, testosterone and prolactin were also determined by radioimmunoassay in 38 patients. Seminal fluid analysis and culture were performed in 35 patients and testicular histology determined in 21. Agglutination was demonstrated in 22 of 50 sera (44%), whilst non-agglutinating cytotoxic antibodies were detected in two. Only two of the 50 control sera (4%) were positive. After steroid therapy, antibody titres were significantly decreased and there was a sixfold improvement in mean sperm concentration and a threefold improvement in motility and morphological characteristics. Bacterial (46%) and non-bacterial (17%) infection were recorded in 22 of 35 patients, 13 of whom showed the presence of antisperm antibodies in their sera. Staphylococcus aureus was the commonest single bacterial isolate. Overall, 13 of 29 patients (45%) improved, nine accounting for 12 pregnancies. Pregnancies and/or improvements in semen quality were observed only among patients with mild histological changes. Low testosterone and prolactinaemia occurred in 29% and 21% of the patients, respectively. Among these, anti-sperm antibodies were also recorded in 18% and 13%, respectively. The incidence of antisperm antibodies among infertile men is high in Nigeria and may be related to high prevalence of STDs. Immunologically infertile men can be treated successfully with steroids. Concomitant antibiotic and hormone therapy may also be essential in appropriate cases. Clinicians are advised to adopt a multimodal approach to the treatment of male infertility in sub-Saharan Africa. The presence of non-agglutinating cytotoxic antibodies calls for further investigation of the role of complement in the pathogenesis of immunological infertility.

Enteral-feeding-related diarrhoea: proposed causes and possible solutions

So to summarize the key points: 1. concomitant antibiotic therapy, infected diets and possibly hypoalbuminaemia can lead to enteral-feeding-related diarrhoea; 2. the small intestinal responses to both intragastric and intraduodenal enteral feeding are normal and predictable; 3. there is an ascending colonic secretion during enteral feeding which is more profound during intragastric feeding; 4. the suppression of distal colonic motor activity occurs only during high-load feeding and is probably a secondary phenomenon to the hormonal and secretory responses; 5. peptide YY appears to be intrinsically bound up with the causation of the secretory effect; 6. the secretory effect is abolished by intracaecal SCFA.

Topical Anti-inflammatory Agents in an Animal Model of Microbial Keratitis

Topical steroids potentiate Pseudomonas keratitis in the absence of concomitant antibiotic therapy. The effects of other anti-inflammatory agents on microbial keratitis are unknown, but if these agents do not intensify the infection, they may be useful in the initial management of microbial keratitis by limiting ulceration and thus the size of the resultant corneal scar. In rabbit models of untreated Pseudomonas keratitis and pneumococcal keratitis, topical 1% prednisolone phosphate, 0.03% flurbiprofen sodium, and vehicle were applied hourly. In cases of Pseudomonas keratitis, prednisolone worsened the clinical disease, and flurbiprofen further worsened the disease. When combined with effective antibiotic therapy, neither anti-inflammatory agent worsened the disease. In pneumococcal keratitis, neither anti-inflammatory agent worsened the disease. Topical anti-inflammatory agents should be used with caution in cases of microbial keratitis at least until effective antibiotic therapy has been instituted.

Evaluation of tetracycline on theophylline disposition in patients with chronic obstructive airways disease.

Theophylline is a commonly used bronchodilator in the treatment of chronic obstructive airways disease (COAD) with a narrow therapeutic range of 10 to 20 micrograms/ml. Patients with COAD frequently receive concomitant antibiotic therapy for respiratory infections. This study evaluated the effect of tetracycline therapy on theophylline disposition in adults with COAD. Six males (five nonsmokers) with obstructive ventilatory defects were studied in two phases: control, after receiving sustained-release theophylline in the same dosage regimen for four days, and treatment, after receiving tetracycline 250 mg po qid for five days in addition to theophylline. During each phase, 10 blood samples were obtained over one dosing interval and analyzed for theophylline content. The following pharmacokinetic parameters were calculated: Cmin, Cmax, Css, percentage fluctuation and Cl. Differences for each value were tested as paired data with Student's two-tailed t-test. When all patients were evaluated, the only statistically significant difference was for Cmax. However, when the five nonsmokers were evaluated separately, differences were observed for Css (micrograms/ml; mean +/- SD) 9.3 +/- 3.0, control, and 10.6 +/- 3.8, treatment (p = 0.041); and for Cl [( ml/h]/kg; mean +/- SD) 49.0 +/- 11.1, control, and 43.6 +/- 10.2, treatment (p = 0.019). This study demonstrates that tetracycline may weakly inhibit theophylline clearance in nonsmoking adults with COAD.

Principles of concomitant antibiotic therapy.

There are five major disadvantages of the combined use of antibiotics: (i) antibiotic antagonism; (ii) a "false sense of security"; (iii) increased toxicity; (iv) suprainfection; and (v) increased cost. Four situations clearly require the use of antibiotic combinations: (i) to produce antibiotic synergism; (ii) to prevent the emergence of resistant organisms; (iii) to treat mixed infections, such as brain abscess, peritonitis, and pelvic infections; and (iv) to institute therapy for severe infections.

The Spectrum of Vitamin K Deficiency

The coagulopathy induced by vitamin K deficiency commonly results from our lack of awareness of the clinical setting associated with vitamin K deficiency. Thirteen cases are reviewed to illustrate the clinical correlates most frequently observed. Dietary deficiency was always present, but concomitant antibiotic therapy was not an absolute requirement. The postoperative patient is at high risk, as is the patient with cancer or renal failure. Abnormal bleeding was common, but significant hemorrhage occurred only in postoperative patients. Factor assays were helpful and occasionally necessary to make the diagnosis, but a therapeutic trial with parenteral vitamin K was often enough to provide the right diagnosis. Greater awareness of this deficiency syndrome is necessary to avoid the serious morbidity that often results.

Osteoplasty and its application in oral surgery

Bone grafting and other osteoplastic procedures are frequently indicated in the practice of oral surgery. Methods of restoring deficient bone that have been reported in the literature have been reviewed. The importance of periosteum, organizing hematoma, and adequate vascular supply to reparative osteogenesis and the bone regeneration that follows osteoplasty has been well documented. Fresh autogenous bone is the best material to use in osteoplasty, but different types of preserved bone, tissue substitutes, and synthetic materials may also be employed. The most frequent indication for a bone-restorative procedure is in the obliteration of cavities of the jaws resulting from the removal of impacted teeth, cysts, and neoplasms. Freeze-dried bone is a practicable material for use in the correction of these defects. Osteoplasty may be successfully performed intraorally when concomitant antibiotic therapy is employed.