Microbiological Assessment of Polymyxin B Components Tested Alone and in Combination.

We investigated the antimicrobial activity of four polymyxin B components, B1, B2, B3, and isoleucine (Ile)-B1, individually and in combination. B3 was the most active agent against all organisms tested except Acinetobacter baumannii, for which Ile-B1 was most active. One combination met the criteria for synergy, B3 plus Ile-B1. No combinations exhibited antagonism. The dominant components of polymyxin B products (B1 and B2) were associated with the lowest probability of improved antibacterial activity when combined.

An update on the arsenal for multidrug-resistant Acinetobacter infections: polymyxin antibiotics.

OBJECTIVE: To review recent clinical pharmacokinetic and pharmacodynamic data to optimize dosing regimens for polymyxin B and colistin for treatment of infections due to A. baumannii. METHODS: A literature search was performed using the search terms Acinetobacter, polymyxin, colistin, polymyxin B on MEDLINE. Additional references were identified from the resulting citations. RESULTS: Increasing the dose of polymyxin B or colistin and using either in combination with other antibiotic agents demonstrates improved antimicrobial activity against Acinetobacter spp. Polymyxin B, unlike colistin, is available as an active drug and appears to be relatively unaffected by renal function. This is advantageous both for patients with renal impairment and for those with intact renal function. Achieving therapeutic serum concentrations of colistin may be difficult for those with intact renal function due to rapid clearance of the prodrug, colistimethate sodium (CMS). Clinical data are still lacking for polymyxin B, and it remains to be seen whether advantages demonstrated in PK/PD analyses will persist in the larger scale of patient care and safety. CONCLUSIONS: The use of higher doses of either colistin or polymyxin B, as well as combination with other antibiotics, may prevent emerging resistance and preserve the activity of polymyxins against A. baumannii.

To B or not to B, that is the question: is it time to replace colistin with polymyxin B?

The polymyxins-colistin and polymyxin B-are an increasingly important part of the antimicrobial arsenal given the rising rate of infections due to multidrug-resistant gram-negative bacteria. Although the drugs have available since the 1950s, only recently have pharmacokinetic and pharmacodynamic data been available to guide appropriate use of these drugs. Far more data and global clinical experience exist for colistin, available as the prodrug colistimethate sodium (CMS), compared with polymyxin B. Concerns raised about variability in the ability to achieve therapeutic drug concentrations when dosing CMS have led many clinicians to desire a more pharmacokinetically reliable product. The pharmacokinetic and pharmacodynamic advantages of polymyxin B compared with CMS are compelling, but clinical experience has not consistently corroborated these data. Prospective, comparative data evaluating both drugs in combination with other antimicrobials as well as comparing polymyxin B and CMS directly will inform optimal use of each drug. Some of these investigations are currently under way. In the meantime, based on current data, both drugs appear to be appropriate for use in the clinical setting.

Polymyxins: wisdom does not always come with age.

We currently face a lack of new antimicrobial therapies in an era of increasingly common multidrug-resistant (MDR) bacteria. The polymyxins have become last-line treatments for patients with MDR bacterial infections. An increasing body of published literature has attempted to answer questions about dosing, pharmacology, and susceptibility testing of these drugs, yet each takes for granted purity and potency of the 2 available polymyxin products. In the case of polymyxin B, true potency may vary by as much as 40% from the content reported in prescribing information. This poor accuracy is related to quality assurance assays established in the 1940s and currently in use, which have been shown to be significantly flawed in recent investigations. This review discusses the limitations of pharmacological knowledge about polymyxin antimicrobials, the clinical impact of these limitations, and suggestions for further study of these drugs in order to optimize their use clinically.

How low can you go? Use of low- and standard-dose liposomal amphotericin B for treatment of invasive fungal infections.

OBJECTIVES: Recommended doses of liposomal amphotericin B (L-AMB) range from 3 to 6 mg/kg/day, but 1mg/kg/day may be equally effective and a lower cost alternative for many indications. The objective of this analysis was to assess indications and clinical outcomes of patients who received low-dose (1mg/kg/day rounded up in 50-mg increments) and standard-dose (≥2 mg/kg/day) L-AMB. METHODS: This was a retrospective analysis of adult L-AMB recipients with suspected invasive fungal infections (IFI) at a single center from 2006 to 2011. The primary outcome was clinical response at the end of treatment. Secondary outcomes included survival and toxicity. Results were analyzed using Chi-square and descriptive statistics. RESULTS: Of 89 adult L-AMB recipients included, 36 had proven or probable IFIs. Nineteen (53%) received low doses and 17 (47%) received standard doses. Median doses were 1.5 and 3.0mg/kg/day. Cryptococcus was the most common fungal pathogen in the low-dose group (37%), and Candida spp. in the standard-dose group (47%). Forty-seven percent of subjects in both groups improved clinically. Sixty-eight percent of low-dose recipients and 76% of standard-dose recipients survived to discharge. Rates of nephrotoxicity and hypokalemia were comparable. CONCLUSIONS: Comparable rates of clinical improvement, survival to discharge, and toxicity were identified among low- and standard-dose L-AMB recipients.

Behind closed doors: medication storage and disposal in the home.

BACKGROUND: More than half of all medications are inappropriately prescribed, dispensed, or sold and only 50% of patients take their medications correctly. Oftentimes, unwanted or expired medications are saved for later use, stored indefinitely, or disposed via the sink, toilet, or garbage. OBJECTIVE: To determine how residents in Cook County, Illinois, use, store, and dispose of their medications to assess the possible impact of these medications on health care and the environment. METHODS: Researchers at the University of Illinois conducted a survey of Cook County residents over a 13-week period. Residents were surveyed regarding their use, storage, and disposal of prescription and nonprescription medications. RESULTS: From 3954 telephone numbers generated through random-digit dialing, 445 telephone interviews were completed. Eighty-one and a half percent of respondents had prescription medications and 92.4% had nonprescription medications in their homes. On average, respondents possessed 4.4 distinct prescription and 5.5 distinct nonprescription medications. Despite possessing a number of medications, approximately 30% of respondents stated that they took no medication on a regular basis; 59% of respondents reported disposing medications in the household gar bage and 31% flushed them down the toilet or sink. Over 80% of respondents stated that they had never received information about proper medication disposal. Thirty-seven percent reported having leftover unexpired medications from a previous illness. Of these, 63% stopped taking their medications because they believed that they no longer needed them or because they felt better. Thirty-two percent of respondents expected to have leftover prescription medications within the next 6 months. CONCLUSIONS: Almost all respondents had excess and leftover medications in their homes. This may be a result of both overprescribing and poor medication adherence. In addition to the potential human health risk of nonadherence, disposal of excess medication raises concerns about their environmental impact and safety.