Overuse and inappropriate prescribing of proton pump inhibitors in patients with Clostridium difficile-associated disease.

BACKGROUND: Clostridium difficile is the most common infectious cause of colitis and has been increasingly diagnosed in hospitalized patients. The number of prescriptions for proton pump inhibitors (PPIs) has also increased significantly over time. Few studies have reported an association between C. difficile-associated disease (CDAD) and PPI use. AIM: To assess the extent and appropriateness of PPI prescribing in patients diagnosed with C. difficile infection. METHODS: We prospectively studied PPI prescriptions in 138 hospitalized patients diagnosed with C. difficile infection over a 4-month period. Clostridium difficile infections were diagnosed by the presence of C. difficile toxin in the stools. The appropriateness of prescriptions and relevant investigations were assessed by interview of patients and review of patient records. RESULTS: Sixty-four percent (88 of 138) of all patients who developed C. difficile infections were on PPIs. A valid indication for PPIs therapy was not apparent in 63% of the patients. CONCLUSION: There appears to be a widespread and inappropriate use of PPIs in hospital practice. Reduction of unnecessary PPIs use may be an additional strategy to reduce the incidence of this infection.

A survey of the management of neutropenic fever in oncology units in the UK.

A nationwide questionnaire-based survey was performed to define the different practices in managing febrile neutropenia in oncology units and the use of antimicrobial chemotherapy prophylaxis. A 69.7% response rate was obtained from a total of 165 units. Fifty percent of the responding oncologists used combination therapy with piperacillin/tazobactam plus gentamicin as a first-line treatment in febrile neutropenia. When response to initial empirical therapy does not occur after 24-48h, 51.3% of oncology units add a glycopeptide (vancomycin or teicoplanin) and 39.2% change to a carbapenem and a glycopeptide. The role of oral antibiotics in managing febrile neutropenia is still low. Approximately 30% of studied units might consider using an oral antibiotic in this setting. When response to initial empirical therapy does not occur after 3-7 days, 46.1% of oncologists preferred liposomal amphotericin to conventional amphotericin (28.7%) in treating persistent febrile neutropenia. The antimicrobial chemotherapy treatment of febrile neutropenia in oncology patients and the use of antimicrobial prophylaxis varies significantly across the UK. This survey is the first to examine the prescribing practices of UK oncology units in this area and could help in the formulation of practice guidelines.

Knowledge about sepsis among training-grade doctors.

BACKGROUND: Prescribing of antibiotics, often in the empirical setting, frequently falls on training-grade or junior doctors, who are often the least experienced in this. Indeed, improving the knowledge base of training-grade doctors or senior medical students through education has been identified as one of the key measures to improve antibiotic prescribing behaviour. METHODOLOGY: We undertook two descriptive questionnaire- and interview-based surveys (1999 and 2003) of prescribing training-grade doctors in a teaching hospital in north-east Scotland to determine their knowledge level regarding various sepsis definitions, sources of local information used when prescribing an antimicrobial, and awareness of the cost difference between intravenous and oral antibiotics. A total of 55 junior doctors in a large teaching hospital participated in the survey in 1999 and 78 participated in 2003. INTERVENTIONS: Between the two audits, which were conducted 4 years apart, several initiatives were introduced to improve the education and support related to antibiotic prescription. RESULTS: There has been a significant improvement in doctors' knowledge regarding various sepsis definitions, whether the infection was hospital or community acquired, empirical choice, dose, route of administration and monitoring of the antibiotic, and options for drug hypersensitivity. More training-grade doctors (approximately 29%) used the desired locally derived sepsis protocol, which guides the prescriber through sepsis recognition. There was no significant improvement in the percentage of doctors who recognized that parenteral antimicrobials were more expensive (approximately 10-fold) than oral antimicrobials (63.7% in 1999, 64.2% in 2003). CONCLUSIONS: Overall, there was a significant improvement in doctors' understanding of sepsis and knowledge of the source of information that they utilized to select the antibiotic of choice, although the majority did not acknowledge the price difference between intravenous and oral forms of antibiotics.

A survey of the antibiotic treatment of febrile neutropenia in haematology units in the United Kingdom.

We performed a nationwide survey to define the different practices in managing febrile neutropenia in haematology units. A questionnaire was sent out to a named haematologist in each of 220 haematology units in the UK. Questions were asked regarding antibiotics of choice in managing febrile neutropenia and the use of antibiotic prophylaxis. Responses were received from 167 (76%) haematology units. Combination therapy with piperacillin-tazobactam and gentamicin is used first-line in febrile neutropenia by 72% of units. Piperacillin-tazobactam monotherapy is used first-line by 5% of units. When response to initial empirical therapy does not occur after 24-48 h, 32% of haematology units add a glycopeptide (vancomycin or teicoplanin) and 31% change to a carbapenem and a glycopeptide. Seventy-one percent of units use oral fluoroquinolone prophylaxis for all neutropenic patients. The antibiotic treatment of febrile neutropenia in haematology patients, and the use of antibiotic prophylaxis, vary significantly across the UK. This survey is the first to examine the prescribing of UK haematology units in this area, and could help in the formulation of practice guidelines.

Clinical audit of linezolid use in a large teaching hospital.

OBJECTIVES: Linezolid, the first available agent in the new class of oxazolidinone antibiotics, represents a significant advance in the management options available for combating methicillin-resistant Staphylococcus aureus (MRSA) infections. In the UK it was launched for clinical use in 2001. The aim of this study was to audit the clinical use of linezolid and compliance with the guidelines of the hospital antibiotic committee. METHODS: Our hospital antibiotic committee agreed clinical indications for linezolid use. We undertook an audit of compliance with these recommendations and also reviewed its use in terms of the source of infection, microbiology, duration of therapy, side-effects and choice of previous treatment. RESULTS: Seventy-seven inpatients prescribed linezolid in Ninewells Hospital in the 3 years between March 2001 and September 2003 were audited. Overall compliance with our local recommendations appears to be very good. The main justification for using linezolid is the presence of existing or worsening renal dysfunction or poor venous access (34%) or lack of tolerance or clinical failure following glycopeptide monotherapy or combination therapy (32%). Skin and soft tissue infections (26%) were the most frequently diagnosed infections, although an increasing number of patients appear to receive linezolid for the treatment of lower respiratory tract infections, primarily in the ICU for nosocomial or ventilator-associated pneumonia. MRSA organisms were the most common cause of microbiologically proven treated infections [n = 43 (56%)]. Disappointingly, only 34 out of 77 patients had case record documentation of prior approval by an infection specialist. CONCLUSIONS: The use of linezolid in our hospital appears to follow local guidelines, but the quality of information recorded in the notes could be optimized. Consequently, a linezolid mandatory order form to be completed by the attending prescribing clinician has been introduced, and will be subject to future evaluation. We recommend such specific antibiotic utilization reviews or audits of new agents introduced into clinical infection practice.

Immunomodulating activity of rifampicin.

It has been shown that some antibiotics can modify cytokine production. We have examined the effect of rifampicin on secretion of interleukin-1beta (IL-1beta), IL-6, IL-10, and tumor necrosis factor alpha (TNF-alpha) by lipopolysaccharide (LPS)-stimulated or heat killed staphylococci (Pansorbin) stimulated monocytes. Secretion of IL-1beta and TNF-a were significantly inhibited (P<0.002) whereas secretion of IL-6 and IL-10 were significantly increased (P<0.003) by rifampicin treated mononuclear cells. Rifampicin had immunomodulatory effects through its capacity to alter the secretion of tested cytokines by human monocytes.

Limitations of presently available glycopeptides in the treatment of Gram-positive infection.

The glycopeptide antibacterial drugs vancomycin and teicoplanin are widely used in hospitals for therapy of severe or multiresistant Gram-positive infections, notably staphylococcal, enterococcal and rarely pneumococcal. Vancomycin has also been used in the management of Clostridium difficile enteropathy. The incidence and potential for resistance differ between agents. The in vitro activity, pharmacokinetics and clinical use of glycopeptide, as well as epidemiology of glycopeptide resistance are discussed. There are limited comparative studies indicating the need for further investigation. Therapeutic drug monitoring has been widely used for vancomycin and less commonly for teicoplanin, but remains controversial. Advances in our understanding of their pharmacodynamics and clinical studies are helping clarify the situation. This paper reviews the current literature and highlights limitations of glycopeptides in treating Gram-positive infection.