Stable, compounded bedaquiline suspensions to support practical implementation of pediatric dosing in the field.

BACKGROUND: Bedaquiline (BDQ) tablets are indicated as part of a combination regimen for the treatment of multidrug-resistant TB in adults, adolescents and children. A dispersible tablet formulation is now approved but is not currently available in all settings. The aim of this study was to develop stable extemporaneous liquid formulations of BDQ that can be stored at room temperature or 30°C for several weeks, to support pragmatic pediatric dosing in the field and reduce wastage.METHODS: BDQ tablets were suspended in simple syrup and a sugar-free vehicle. Each 20 mg/mL formulation was stored at room temperature or 30°C for 30 days in amber dispensing bottles. Appearance, BDQ potency, pH and microbial counts were determined on Days 0, 15 and 30.RESULTS: The BDQ potency in both formulations remained at 98-101% of the theoretical concentration for 30 days. The appearance, pH and microbial count of sugar-free formulation did not change during the 30-day storage. The simple syrup formulation was stable for 15 days as microbial growth was observed on Day 30.CONCLUSIONS: BDQ may be prepared in syrup or sugar-free suspensions: syrup suspensions can be stored for 15 days at room temperature and 30C, whereas sugar-free suspensions can be stored for 30 days at room temperature and 30C. This information will support practical BDQ dosing for children in the field.

Extemporaneously compounded liquid formulations of clofazimine.

BACKGROUND: Clofazimine (CFZ) is routinely used worldwide for the treatment of leprosy and TB. However, no liquid or dispersible tablet formulations of CFZ are currently available commercially for patients with challenges ingesting soft gelatin capsules or solid formulations. The aim of this research was to develop stable extemporaneous liquid formulations of CFZ that can be stored at room temperature for several weeks to enable practical dosing in the field. METHODS: Two formulations were prepared in syrup and sugar-free vehicles with CFZ tablets using a simple method that can be used in a routine pharmacy. Suspensions were stored at room temperature and at 30°C for 30 days. Formulation aliquots were tested on Days 0, 15 and 30 for appearance, pH, potency and microbial counts. RESULTS: Appearance remained unchanged during storage. The pH of both formulations was between 4.0 and 6.0. Potency was between 90% and 110% for 30 days in the syrup formulation and for 15 days in the sugar-free formulation. Microbial counts met United States Pharmacopeia 1111 limits for oral aqueous liquids and specific organisms were absent. CONCLUSIONS: A simple field-friendly method was successfully developed for the preparation of CFZ liquid formulations using commonly available ingredients. This will permit practical dosing and titration for children and other patients with swallowing challenges.

Sugar and sugar-free liquid formulations of delamanid for patients with rifampicin-resistant TB.

BACKGROUND: Delamanid (DLM) tablets are recommended for the treatment of rifampicin-resistant TB. However, no liquid or dispersible tablet formulation of DLM is currently commercially available for patients with challenges ingesting these tablets. The aim of this study was to develop stable extemporaneous liquid formulations of DLM that can be stored at room temperature for several weeks.METHODS: DLM tablets were suspended in 1) simple syrup and 2) a specially formulated sugar-free vehicle. These suspensions containing DLM 5 mg/mL were stored in plastic prescription bottles at room temperature or 30°C for 30 days. These suspensions were evaluated for appearance, potency, pH, and microbial counts at Days 0, 15, and 30.RESULTS: The potency of DLM in each formulation remained at 98-104% of the theoretical concentration for 30 days. The appearance, pH, and microbial count did not change for the sugar-free formulation during the 30-day storage period. Microbial growth, however, was observed in the simple syrup formulation on Day 30 but not on Day 15.CONCLUSION: DLM can be formulated in sugar or sugar-free suspensions and stored at room temperature or 30°C for at least 15 and 30 days, respectively.

A novel home-based method for preparing suspensions of anti-TB drugs.

BACKGROUND: Tablets are the most widely available dosage form for the treatment of TB; however, adult tablets fail to meet the needs of young children who cannot swallow these tablets or require dose titration. We tested a new, simple device (XTEMP-R®) and the methodology for converting tablets of TB drugs into a homogeneous suspension for home use by children and caregivers.METHODS: XTEMP-R is a new device used for converting tablets into liquid preparations. Four TB drugs - pretomanid, delamanid, clofazimine and bedaquiline - were dispersed in the device utilizing water and simple syrup. The reproducibility of accurately delivering aliquots from the suspension upon preparation and upon redispersion after storing for 2 days was studied.RESULTS: Suspensions of each of the drugs tested were easily prepared in about 10 min and were visually uniform in consistency. Dosages in 2 and 5 mL were assessed in suspension, and those in 5 mL tested upon redispersion after 2 days. The observed range for these dosages spanned from 94.6% to 101.1% of the theoretical concentration for the suspensions under examination. The cleaned device had no detectable residual drug.CONCLUSION: XTEMP-R can be used at home by caregivers to prepare doses of suspensions accurately for children and patients who cannot swallow tablets.

Stable sugar and sugar-free suspensions of pretomanid.

BACKGROUND: Pretomanid (PMD) tablets are indicated as part of a combination regimen for the treatment of adults with pulmonary extensively drug-resistant, treatment-intolerant or non-responsive multidrug-resistant TB. No commercial liquid formulation is currently available for patients unable to swallow these tablets.OBJECTIVE: To develop stable extemporaneous liquid formulations of PMD that can be stored at room temperature or 30°C for at least 4 weeks.METHODS: Crushed PMD tablets were formulated into 20 mg/mL suspensions in a simple syrup and sugar-free formulation. The PMD formulations were stored at room temperature and at 30°C for 30 days in dispensing bottles. Appearance, pH, potency and microbial counts of the suspensions were determined on Days 0, 15 and 30.RESULTS: The potency of PMD remained at 99.7-103.4% of the theoretical concentration in each formulation. The appearance, pH and microbial count did not change during the 30-day storage period. Simple syrup formulations did not require preservatives for microbial stability.CONCLUSIONS: PMD oral suspension formulations in simple syrup or in sugar-free vehicle were easily prepared by utilising commonly available equipment and ingredients and were stable for 30 days. These formulations are appropriate alternatives for patients with swallowing difficulties.

Treatment of irritable bowel syndrome.

WHAT IS KNOWN AND OBJECTIVE: The complexity and diversity of irritable bowel syndrome's (IBS) presentation make treatment difficult. Although there are reviews and guidelines for treating IBS, they focus on the efficacy of medications for IBS symptoms using high-priority endpoints, leaving those of lower priority largely unreported. Therefore, the aim of this review is to provide a comprehensive evidence-based review of the efficacy of medications to treat IBS symptoms, reported by IBS subtype, including secondary symptom endpoints that are often underreported. METHODS: A review of PubMed for articles published through December 2009 using the keywords: 'irritable bowel syndrome', 'therapeutics', 'antidiarrhoeals', 'laxatives', 'loperamide', 'dietary fibre', 'psyllium', 'calcium polycarbophil', 'bulking agents', 'lubiprostone', 'antidepressant agents, tricyclics' and its representative entities, 'serotonin reuptake inhibitors' and its representative entities, 'dicyclomine', hyoscyamine', 'peppermint oil', 'parasympatholytics' and its representative entities, 'rifaximin', 'pregabalin', 'gabapentin', 'clonidine', 'octreotide', 'atropine' and 'probiotics' is provided. Placebo-controlled trials were evaluated for the strength of evidence supporting the efficacy of each medication for explicit IBS symptoms. The efficacy of each medication for the symptoms of abdominal pain, bloating, stool form, mucus, urgency, feeling of incomplete evacuation, flatulence, frequency, or borborgymi and overall symptoms are reported by IBS subtype. RESULTS AND DISCUSSION: The literature search identified 58 placebo-controlled trials of the efficacy of medications for treating IBS symptoms, which were critically evaluated and reported. The available studies suggest improvement in various IBS symptoms with loperamide, fibre supplements, lubiprostone, tricyclic antidepressants (TCAs), selective serotonin receptor inhibitors (SSRIs), antispasmotics, rifaximin, pregabalin, gabapentin, clonidine, octreotide and probiotic treatments. WHAT IS NEW AND CONCLUSION: This review is the first to compile the available evidence on the efficacy of the various pharmacological treatments for IBS on the basis of IBS subtype and specific symptoms. This evidence is limited and more well-designed studies are required to better inform therapeutic decision-making in the management of this difficult syndrome.

Noneffect of oral urinary copper ascorbic acid on reduction glucose test.

References and texts in the fields of diabetes and clinical chemistry commonly report that ascorbic acid when given orally or parenterally gives a false-positive reaction to the copper reduction glucose test (Clinitest). This impression is based on a study in which ascorbic acid (250 mg./dl.) was added to urine in vitro, with a resultant positive-test reading in the absence of glucose. Ascorbic acid is a reducing agent, and theoretically it could interfere with the copper reduction method of glucose detection. In the current study 10 nondiabetic men were ingesting 4 and 6 gm. ascorbic acid per day. A total of 360 glucose detection tests with the copper reduction method were undertaken. In no instance was there a positive reaction to the glucose test.

Prescription order risk factors for pediatric dosing alerts.

OBJECTIVES: To determine dosing alert rates based on prescription order characteristics and identify prescription order risk factors for the occurrence of dosing alerts. METHODS: A retrospective analysis of inpatient medication orders and dosing alerts occurring during October 2011 and January, April, and July 2012 at a pediatric institution. Prescription orders and alerts were categorized by: medication class, patient age, route of administration, and month of the year. RESULTS: There were 228,259 orders during the studied period, with 11,072 alerted orders (4.9%). The most frequently alerted medication class was the non-analgesic central nervous system agent class (14% of alerts). Age, route, medication class, and month all independently affected dosing alert rates. The alert rate was highest for immunosuppressive agents (54%), neonates (6.7%), and orders for rectal administration (9.5%). The alert rate was higher in adult patients receiving their care at a pediatric institution (5.7%) compared to children (4.7%), but after multivariate analysis, pediatric orders had higher odds for an alert (OR 1.1, 95% CI 1.05-1.16). Mercaptopurine had the highest alert rate when categorized by active ingredient (73.9%). Albuterol 2.5mg/mL continuous aerosol and heparin 1000 units in 0.9% sodium chloride injection solution were the unique medications with the highest alert rates (100.0% and 97.7%, respectively). CONCLUSIONS: Certain types of prescription orders have a higher risk for causing dosing alerts than others. Patient age, medication class, route of administration, and the month of year can affect dosing alert rates. Design and customization efforts should focus on these medications and prescription order characteristics that increase the risk for dosing alerts.

Bioavailability and clearance of chloramphenicol after intravenous chloramphenicol succinate.

Bioavailability of chloramphenicol and kinetics of chloramphenicol succinate and chloramphenicol were studied in 12 patients. Chloramphenicol succinate, 25 mg/kg, was injected intravenously every 6 hr over 0.5 to 1 hr. Both the drug and the prodrug were analyzed by high-pressure liquid chromatography. Bioabailability of chlorampenicol ranged from 0.55 to 0.92 and total, renal, and nonrenal clearance from 6.81 to 98.22, 2.54 to 26.90, and 3.73 to 87.38 ml/m2/min, while clearances of chloramphenicol succinate ranged from 84.75 to 916.00 28.40 to 312.00, and 26.06 to 760.93 ml/m2/min. Urinary recovery of chloramphenicol was 3% to 25% and that of chloramphenicol succinate was 7% to 45%. Mean apparent volumes of distribution were 0.71 l/kg for chloramphenicol and 2.10 l/kg for chloramphenicol succinate and elimination half-lifes were 4.03 and 2.65 hr, respecitively. There were relationships between patient age and clearance of both drugs. Incomplete bioavailability of chloramphenicol and the more than 10-fold variability in clearance of both chloramphenicol and chloramphenicol succinate explain the need for individualizing doses to achieve thrapeutic effect and minimize the risk to toxicity.

Chloramphenicol serum concentration falls during chloramphenicol succinate dosing.

Chloramphenicol succinate and chloramphenicol kinetics were examined on two occasions at steady state, separated by 2 to 17 days, in 10 pediatric patients on the same intravenous dose of chloramphenicol succinate. The steady-state peak serum concentration of chloramphenicol succinate fell from an average of 77.1 micrograms/ml during the first study to 42.2 micrograms/ml during the second. The steady-state peak serum concentration of chloramphenicol also decreased from an average of 27.8 micrograms/ml to 24.9 micrograms/ml. There was a marked decrease in the steady-state trough serum concentration of chloramphenicol, which averaged 8.4 micrograms/ml during the first and 5.3 micrograms/ml at the time of the second study. Mean area under the serum concentration-time curve (AUC) of chloramphenicol succinate decreased from 59.7 micrograms . hr/ml to 24.0 micrograms . hr/ml. The AUC of chloramphenicol averaged 105.7 micrograms . hr/ml at the time of the first and decreased to 79.5 micrograms . hr/ml during the second study. Mean percent decrease in the AUC of chloramphenicol was about 28% and occurred most substantially in patients with high AUCs during the first study. Mean elimination chloramphenicol half-life was 3.0 hr during the first study and fell to 2.3 hr at the time of the second study. Our data indicate that chloramphenicol serum concentration should be monitored frequently, especially in patients not responsive to a set dose.

Moxalactam epimer kinetics in children.

The kinetics of the R and S epimers of moxalactam were followed after single intravenous doses of 50 mg/kg to 12 patients, 8 to 45 mo old, with cellulitis or epiglottitis. High-pressure liquid chromatography was used to determine serum concentrations. Total body clearance and apparent volume of distribution of the R epimer were higher than those of the S epimer (P less than 0.004). Total body clearance of R, S, and R + S moxalactam ranged from 29.01 to 183.7, 19.00 to 79.95, and 23.34 to 113.6 ml/min/m2. Mean elimination half-lives of R, S, and R + X moxalactam were 2.04, 2.26, and 2.24 hr. The higher incidence of the more active R epimer and the 500% interpatient variation in clearance may indicate a need for monitoring serum and cerebrospinal fluid concentrations in patients with severe unresponsive central nervous system infectious treated with moxalactam.

Variations in glycerol kinetics in Reye's syndrome.

Glycerol kinetics and adverse affects were studied in nine patients with Reye's syndrome. Glycerol was given by continuous infusion over 2 hr, half over the first 0.5 hr and the remainder over the next 1.5 hr. The dose was adjusted to keep intracranial pressure less than or equal to 15 mmHg. At steady state, serial blood samples were collected during glycerol infusion and analyzed by an enzymatic assay specific for glycerol. At 0.75 to 1.75 gm/kg/2 hr glycerol doses, the serum levels ranged from 1.48 to 5.83 mg/ml. Total body clearance ranged from 1.99 to 5.1 ml/kg/min. Glycerol clearance was not related to serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), or serum ammonia levels. Glycerol provided effective control of intracranial pressure in all patients. Temporary elevation of serum creatinine and blood urea nitrogen (BUN) and presence of hemolysis in two patients, appeared to be related to glycerol.

Lack of pediatric drug formulations.

Many drugs frequently used in infants and young children are not available in suitable dosage forms. Liquid dosage forms must be prepared extemporaneously, while using appropriate excipients. However, it is critical to determine the stability of various drugs at clinically important concentrations and practical storage conditions. It is of concern that few funding agencies are willing to support research on the development of stable liquid dosage forms for pediatric patients. The need for such data will continue, because it is unlikely that all drugs approved for adults will also be labeled simultaneously for potential use in infants and children. Presentations and publications on stable drug formulations will offer the opportunities for pediatric patients to receive the desired drugs and doses most effectively and safely.

Intravenous infusion conditions. Implications for pharmacokinetic monitoring.

Drugs are often given intravenously with an expectation that the predicted serum concentrations will be achieved rapidly. Routine pharmacokinetic monitoring of some drugs may be of limited value, unless the effect of intravenous drug delivery systems on serum concentrations is known. In vitro studies have demonstrated that the actual time for complete drug delivery can be markedly longer than predicted and is dependent inter alia on factors including the delivery device, flow rate, injection site, drug volume and tubing diameter. Studies in paediatric patients have shown that the serum concentrations of drugs, including aminoglycosides and chloramphenicol, are strongly influenced by intravenous drug delivery systems. Similarly, data from adult patients have indicated that a drug delivery system can affect serum concentrations of aminoglycosides. Some data are available about the pharmacokinetics of drugs delivered by newer devices, e.g. controlled release infusion systems, membrane devices and implanted pumps, but additional research is needed to determine their predictability of delivery and pharmacokinetics of commonly used drugs. To achieve optimal therapeutic outcomes in patients, it is crucial to understand the impact of an intravenous drug delivery system on serum concentrations and to develop guidelines for pharmacokinetic monitoring.

Clinical pharmacokinetics of antibacterial drugs in neonates.

Neonatal patients are surviving longer due to the rapid advances in medical knowledge and technology. Our understanding of the developmental physiology of both preterm and full term neonates has also increased. It is now apparent that differences in body composition and organ function significantly affect the pharmacokinetics of antibacterial drugs in neonates, and dosage modifications are required to optimise antimicrobial therapy. The penicillins and cephalosporins are frequently used in neonates. Although ampicillin has replaced benzylpenicillin (penicillin G) for empirical treatment of neonatal sepsis, many of the other penicillins may be used in neonates for the management of various infections. Increased volume of distribution (Vd) and decreased total body clearance (CL) affect the disposition of penicillins and cephalosporins. Decreased renal clearance (CLR) due to decreased glomerular filtration and tubular secretion is responsible for the decreased CL for most of the beta-lactams. Aminoglycoside Vd is affected by the increased total body water content and extracellular fluid volume of neonates. The increased Vd, in part, accounts for the extended elimination half-life (t1/2) observed in neonates. Aminoglycoside CL is dependent on renal glomerular filtration which is markedly decreased in neonates, especially those preterm. These drugs appear to be less nephrotoxic and ototoxic in neonates than in older patients, and the role of serum concentration monitoring should be limited to specific neonatal patients. Other antibiotics such as vancomycin, teicoplanin, chloramphenicol, rifampicin, erythromycin, clindamycin, metronidazole and cotrimoxazole (trimethoprim plus sulfamethoxazole) may be used in certain clinical situations. The emergence of staphylococcal resistance to penicillins has increased the need for vancomycin. With the exceptions of vancomycin and chloramphenicol, the efficacy and safety of these other agents in neonates have not been established. The need for serum vancomycin concentration monitoring may be limited, as with aminoglycosides, while safety concerns warrant the routine monitoring of serum chloramphenicol concentrations in neonates. Dosing guidelines are provided, based on the pharmacokinetics of the drugs and previously published recommendations. These dosing guidelines are intended for initial therapy, and close therapeutic monitoring is recommended for maintenance dose requirements to optimise patient outcome. There has been an enormous increase in our knowledge of neonatal physiology and drug disposition. Fortunately, many of the antibacterial drugs used in neonates (e.g. penicillins and cephalosporins) are relatively safe. It will be important to evaluate all newly developed antibiotics in neonates to assure their maximum efficacy and safety.

Comparative palatability of 22 liquid antacids.

OBJECTIVE: To compare the palatability, acid neutralizing capability, and costs of different antacids. METHODS: Volunteers between the ages of 18 and 60 years were given 22 antacids. All antacids were given during a 4-h period in two groups of 11 antacids each. Subjects sampled each antacid in a manner similar to wine tasting and rated each antacid on its smell, taste, texture and aftertaste using a scale of 1-9; 1 being the worst and 9 the best. RESULTS: A total of 73 adults completed the study. Mylanta Lemon Twist and Mylanta Cherry Crème were the most palatable antacids; however, overall the palatability of all the antacids was poor. Maalox MS Cool Mint and ES Gaviscon were the least palatable. The extra strength antacids had the most acid neutralizing capability, and thus would require smaller doses. Amphogel was the most costly antacid per mEq of acid neutralized. Age and gender did not affect the palatability scores. CONCLUSION: Although the regular strengths of Mylanta Lemon Twist and Mylanta Cherry Crème were the most palatable, the extra strength versions of these products have twice the acid neutralizing capability and thus, half the volume is required for each dose. Therefore, these agents may be the antacids of choice.

Pharmacokinetics and safety of tobramycin after once-daily administration in patients with cystic fibrosis.

STUDY OBJECTIVE: Tobramycin is commonly used to treat respiratory tract infections in patients with cystic fibrosis. We designed a study to determine the pharmacokinetics and safety of once-daily dosing of tobramycin in this population. DESIGN: Multiple blood samples were collected from each patient, and serum concentrations of tobramycin were determined by a fluorescence polarization immunoassay. Blood urea nitrogen and serum creatinine levels were measured every 2 to 3 days, and audiometric evaluations were performed at the start and end of therapy. MEASUREMENTS AND RESULTS: Eighteen patients (mean age, 24.6 years) received tobramycin at doses of 7 to 15 mg/kg/d as a single-dose infusion over 20 min. The maximum serum concentration of tobramycin ranged from 40.1 to 64.6 mg/L. A mean dose of 11.9+/-1.9 mg/kg was needed to obtain a theoretical mean peak serum concentration of 42.4+/-4.5 mg/L. The mean total body clearance, apparent volume of distribution, and elimination half-life was 1.7+/-0.4 mL/min/kg, 0.27+/-0.06 L/kg, and 1.8+/-0.3 h, respectively. The period of time that the serum concentration exceeded eight times the theoretical minimum inhibitory concentration of 1 mg/L ranged from 2.1 to 4.4 h, which was nearly five times longer compared with the use of divided daily doses in the same patients during previous hospitalizations. No nephrotoxicity, ototoxicity, or adverse effects occurred in any patient. CONCLUSION: Based on our data, tobramycin may be used safely in once-daily doses to treat exacerbations of respiratory tract infections in patients with cystic fibrosis.

Pharmacotherapy of lower limb diabetic ulcers.

OBJECTIVE: To discuss the pathophysiology, microbiology, and pharmacotherapy of lower extremity (LE) diabetic ulcers. DATA SOURCES: A MEDLINE search from 1966 to April 1999 was conducted. The search was limited to humans and English-language journals. Key search words included "diabetic ulcer," "fluoroquinolones," "beta-lactam," "hyperbaric oxygen," "diabetes mellitus," "diabetic foot," and "growth factor." STUDY SELECTION: Randomized and nonrandomized studies were selected for review. Results of randomized, placebo-controlled studies were emphasized more than nonrandomized results. DATA SYNTHESIS: LE ulcers are a common cause of hospitalization, and cause significant morbidity and mortality. Staphylococcus aureus is the most common pathogen in non-limb-threatening infections; Gram-negative bacteria and anaerobes are most prevalent in limb-threatening and life-threatening infections. Oral antibiotic therapy may be used in non-limb-threatening infections, if adequate response is achieved in 24-48 hours; otherwise, intravenous antibiotics should be started. Intravenous antibiotics should be the initial therapy for limb-threatening or life- threatening ulcers. Antimicrobial therapy of at least 10-14 days has been effective in treating LE ulcers in the absence of osteomyelitis. Growth factors offer another treatment alternative, although only becaplermin is currently approved for diabetic ulcers. CONCLUSION: Antibiotic therapy has been effective for the treatment of LE diabetic ulcers. However, further studies are required to identify optimal antibiotics and dosage regimens. Growth factors may have a role but additional research is needed to determine when best to initiate this therapy.

Lack of effect of ascorbic acid, hippuric acid, and methenamine (urinary formaldehyde) on the copper-reduction glucose test in geriatric patients.

Ascorbic acid and hippuric acid (from cranberry juice) are commonly used to acidify the urine for the purpose of enhancing the degradation of therapeutic methenamine mandelate to urinary formaldehyde. A study was made of 27 nondiabetic geriatric patients with indwelling Foley catheters and chronic bacteriuria who were treated with methenamine mandelate (4 gm), ascorbic acid (4 gm), and cranberry cocktail (1 liter) daily. All of 972 urine samples showed formaldehyde in mean concentrations between 14 and 25 microgram/ml. No glucose was found when the urine was tested by the copper-reduction method. In vitro false positive reactions reported in the literature do not appear to be duplicated as an in vivo problem.

Predictability of methenamine efficacy based on type of urinary pathogen and pH.

This study involved 27 geriatric patients with asymptomatic chronic bacteriuria; all had indwelling Foley catheters. The treatment regimens (daily oral dosage) were: methenamine mandelate (MM) granules, 4 gm; MM, 4 gm, plus ascorbic acid, 4 gm; and MM, 4 gm, plus ascorbic acid, 4 gm, plus cranberry cocktail, 1 liter--administered according to a cross-over design. Proteus vulgaris, Pseudomonas aeruginosa and E. coli were the most common urinary organisms. Proteus organisms were more often found in alkaline than in acidic urines, but the type of pathogen had no influence on urinary pH. Urinary formaldehyde concentration [HCHO] was lower in patients with Proteus infection (17.7 micrograms/ml) than in those with Pseudomonas (21.9 micrograms/ml) or E. coli infection (21.8 micrograms/ml). However, for Proteus infection, [HCHO] was higher in patients receiving MM plus ascorbic acid than in those receiving MM alone. Addition of cranberry cocktail to ascorbic acid did not enhance urinary pH, [HCHO] or methenamine efficacy. Our data suggest that in Foley catheter patients with chronic asymptomatic bacteriuria secondary to Proteus, Pseudomonas or E. coli infection, the type of urinary pathogen or the urinary pH cannot be used to predict the efficacy of methenamine therapy either with or without urinary acidifying agents.