Optimal dose of vancomycin for treating methicillin-resistant Staphylococcus aureus pneumonia in critically ill patients

A prospective cohort study was performed to determine the optimal dose of vancomycin to maintain a serum trough concentration of at least 15 to 20 mg/l and to assess the efficacy of this target vancomycin concentration in the treatment of methicillin-resistant Staphylococcus aureus pneumonia. Vancomycin pharmacokinetic parameters were estimated using a CAPSIL software program from serum concentrations of 141 patients with pneumonia treated with vancomycin, regardless of methicillin-resistant Staphylococcus aureus status, at a 28-bed medical intensive care unit. Vancomycin trough concentrations and other pharmacokinetic parameters were compared between five groups of patients differing in their renal function: (1) creatinine clearance > or =60 ml/minute, (2) creatinine clearance 30 to 60 ml/minute, (3) creatinine clearance <30 ml/minute, (4) on intermittent haemodialysis, and (5) on continuous renal replacement therapy. More than 70% of patients failed to reach the recommended therapeutic serum trough concentrations: a higher dose of vancomycin is necessary to maintain serum trough concentration at 15 to 20 mg/l, particularly in critically ill patients with creatinine clearance above 60 ml/minute and in those on intermittent haemodialysis. Among patients with methicillin-resistant Staphylococcus aureus pneumonia, no significant differences were observed in the treatment success rate, length of intensive care unit stay, and intensive care unit mortality rate between patients with vancomycin trough concentrations of >20 mg/l, 15 to 20 mg/l and <15 mg/l.     

Comparison of 3 vancomycin dosage regimens during hemodialysis with cellulose triacetate dialyzers: post-dialysis versus intradialytic administration

AIMS: Traditionally, vancomycin is administered following dialysis to minimize drug loss when high-flux membranes are employed. Unfortunately, this approach is extremely inconvenient for patients and staff, requiring the patients to remain in the unit for at least 1 hour following dialysis. This study was designed to evaluate the feasibility of administering vancomycin during hemodialysis. Specifically, this study was designed to compare the pharmacokinetics of vancomycin when administered during the last 1-2 hours of dialysis (i.e. intra-dialytic administration) to that administered after completion of dialysis. MATERIALS AND METHODS: In a randomized, 3-way crossover trial, the pharmacokinetics of vancomycin were evaluated in 9 hemodialysis patients, comparing vancomycin 15 mg/kg following dialysis (Phase I), vancomycin 15 mg/kg during the last hour of hemodialysis (Phase II) or vancomycin 30 mg/kg during the last 2 hours of hemodialysis (Phase III). Vancomycin plasma concentrations were obtained over an 8-day period and subsequent comparisons between the treatment approaches were made with paired t-tests or ANOVA, as appropriate. Dialysate vancomycin concentrations determined on Day 1 and Day 3 of Phases II and III were used to calculate the fraction of vancomycin dose removed, and were compared to plasma data using paired t-tests. RESULTS: Vancomycin was significantly removed (33.4 to 39.5%) during a 3- to 4-hour high-flux dialysis session occurring on Day 3 after vancomycin administration. Mean serum concentrations immediately following intradialytic vancomycin administration of 15 mg/kg over the last hour of dialysis or 30 mg/kg over the last 2 hours of dialysis were initially high (77.7 and 95.5 mcg/ml respectively), but fell to 25.9 and 40.5 mcg/ml, respectively, by 4 hours post-dialysis. Predialysis concentrations on Days 3, 5 and 8 were similar for vancomycin 30 mg/kg administered over the last 2 hours of dialysis as compared with a 15 mg/kg dose given after dialysis. Vancomycin 15 mg/kg over the last hour of dialysis resulted in significantly lower subsequent predialysis concentrations than the other dosing schemes. CONCLUSIONS: Vancomycin administration of 30 mg/kg over the last 2 hours of dialysis achieves serum concentrations similar to conventional dosing of 15 mg/kg after dialysis and would allow dosing on a weekly basis.     

Serum and dialysate concentrations of cephalexin following repeated dosing in CAPD patients

Oral cephalexin, 1 to 2 g daily for 3 days, was given to six stable, noninfected patients receiving maintenance continuous ambulatory peritoneal dialysis (CAPD). The peak serum concentration after a 2 g initial dose was between 73 and 123 mg/L. On the second and third day in five patients who received a 2 g daily oral dose, the serum concentrations were between 35 and 118 mg/L in serum obtained 1 to 1.5 hours after the dosing. Similar serum concentrations were seen in one patient who only received a 1 g oral dose on the second and third day. Cephalexin concentrations in the peritoneal dialysate reached a peak on the first day between 4 to 14 hours after the dose and were between 31 to 78 mg/L. During the second and third day, the highest cephalexin concentration was 118 mg/L and the lowest was 12 mg/L. The data are consistent with the feasibility of oral cephalexin for treatment of CAPD-associated peritonitis with microorganisms that are sensitive to these levels of cephalexin.     

Doxycycline in serum and bronchial secretions.

The concentration of doxycycline hydrochloride was measured in serum and bronchial secretions in five patients with chronic bronchitis receiving doxycycline orally in normal therapeutic dosage for seven days (200 mg day 1, 100 mg days 2 to 7). After the loading dose of 200 mg, serum concentrations ranged between 5-40 and 3-45 mug/ml (mean 4-33 mug/ml) at 3 hours, declining to between 2-28 and 1-21 mug/ml (mean 1-71 mug/ml) at 23 hours. The mean serum levels for days 2 to 7 were 2-15, 1-79, and 1-38 at 3, 8, and 23 hours respectively. There was considerable individual variability and a wide range of concentrations of doxycycline in the sputum (0-07 to 2-10 mug/ml, mean 0-34 mug/ml). During the course of treatment there was a progressive increase in sputum levels and sputum/serum concentration ratios. There was no correlation between sputum concentration and degree of purulence. The clinical efficacy of doxycycline does not appear to be related to sputum concentration, although the progressive increase in sputum doxycycline levels may be relevant in preventing recurrence of acute infection when the drug is administered as long-term prophylactic therapy.     

The use of glycopeptides in intensive care and anaesthesia

With the objective of clarifying the modes of using glycopeptides in intensive care, a survey with a declared intention was performed in June 2001, in the form of a postal questionnaire; it was possible to exploit 742 answers. Analysis of the results showed that 15% of the doctors completing the questionnaire had not employed glycopeptides within the past six months. Preference was given to vancomycin, and 65% of practitioners prescribed this drug only, while 1% of them only prescribed teicoplanin. For vancomycin, a central route is used in 9 out of 10 cases, with a preference for continuous infusion (69% versus 48%). A loading dose is prescribed in 70% of continuous infusions (> or = 15 mg.kg-1 in 69% of cases), and in 19% of intermittent infusions (> or = 15 mg.kg-1 in 90% of cases). The mean vancomycin dosage is 30 mg.kg-1.d-1; in the case of intermittent administration this involves two (51%), three (17%) or four (27%) injections per day. The target concentrations are residual serum vancomycin levels of between 13.5 and 23.6 mg.L-1 with intermittent administration or plateau levels of 18.3 to 29.4 mg.L-1 with continuous infusion. Teicoplanin is administered intravenously (92%) and/or via the i.m. route (34%). The mean dosage is < 10 mg.kg-1.d-1 in seven out of ten cases. A loading dose is administered every 12 hours at the same dosage in 77% of cases (< or = 3 injections for 65% of prescribers). The residual teicoplanin concentrations sought are between 14.3 and 25 mg.L-1. Monitoring of serum levels is ensured at least once a week in 97% of cases with vancomycin and 66% of cases with teicoplanin. In conclusion, is seems that the methods of using glycopeptides vary considerably. The great heterogeneity of practices suggests a lack of compliance by prescribing practitioners with current recommendations. It also seems that a precise definition of the target plasma levels to be achieved in different indications is necessary.     

Clinical pharmacology of intravenous and intraperitoneal aminoglycoside antibiotics in the prevention of wound infections.

Seventeen patients had intraoperative peritoneal lavage with a solution containing one gram of kanamycin in 200 ml of 0.9% NaCl. The solution was removed by suction at two or five minutes. Venous blood samples were obtained at 15 minute intervals for two hours following lavage. Despite diligent attempts, an average of only 60% of the solution was recovered by suction. The peak concentration of kanamycin in serum correlated directly with the kanamycin dose (p less than 0.025). In six patients lavaged for five minutes, peak absorption occurred at 15 minutes with serum concentrations of 20.3 +/- 2.0 microgram/ml. In five patients lavaged for two minutes insignificantly (p greater than 0.1) lower peak serum concentrations (15.3 +/- 1.8 microgram/ml) occurred at 15 minutes. Six additional patients had peak kanamycin serum concentrations which occurred at 75 minutes and reached 23.2 and 24.0 microgram/ml in two patients. In three patients who received intravenous gentamicin prior to surgery, nine paired serum and peritoneal fluid samples obtained during three hours preceding lavage showed no significant differences in gentamicin concentrations (p less than 0.5). These pharmacokinetic data demonstrate the penetration of parenterally administered aminoglycosides into intraoperative peritoneal fluid. Kanamycin lavage for wound prophylaxis should be used cautiously and should be abandoned in patients who have renal impairment where prolonged toxic serum concentrations could develop.     

Treatment of staphylococcal ventriculitis associated with external cerebrospinal fluid drains: a prospective randomized trial of intravenous compared with intraventricular vancomycin therapy

OBJECT: Staphylococcal ventriculitis may be a complication in temporary external ventricular drains (EVDs). The limited penetration of vancomycin into the cerebrospinal fluid (CSF) is well known; the pharmacodynamics and efficacy of systemically compared with intraventricularly administered vancomycin is examined in this prospective study. METHODS: Ten patients in whom EVDs were implanted to treat intracranial hemorrhage and who were suffering from drain-associated ventriculitis were randomized into two treatment groups. Five of these patients (median age 47 years) were treated with 2 g/day vancomycin administered intravenously (four infusions/day, Group 1), and the other five(median age 49 years) received 10 mg vancomycin intraventricularly once daily (Group 2). Vancomycin levels were measured in serum and CSF six times a day. The maximum vancomycin level in CSF was 1.73 +/- 0.4 micro/ml in Group 1 and 565.58 +/- 168.71 microg/ml 1 hour after vancomycin application in Group 2 (mean +/- standard deviation). Vancomycin levels above the recommended trough level of 5 microg/ml in CSF were never reached in Group 1, whereas in Group 2 they below the trough level (3.74 +/- 0.66 microg/ml) only at 21 hours after intraventricular vancomycin application. The vancomycin level in the serum was constant within therapeutic levels in Group 1, whereas in Group 2 in most instances vancomycin was almost below a measurable concentration. In both groups bacteriologically and laboratory-confirmed CSF clearance could be obtained. CONCLUSIONS: Intraventricular vancomycin application is a safe and efficacious treatment modality in drain-associated ventriculitis, with much higher vancomycin levels being achieved in the ventricular CSF than by intravenous administration.     

Candida septic thrombosis of the great central veins associated with central catheters. Clinical features and management.

Candida septic thrombosis of the great central veins is rarely diagnosed during life, and reports of survival with this condition are exceedingly rare. Eight patients with Candida septic thrombosis of the central veins, with six survivors, are reported. Seven of eight patients had multiple organ system failure following surgery or trauma. All patients had received broad spectrum antibiotics and total parenteral nutrition via a central catheter. Every patient showed features of venous thrombosis with localizing extremity edema and high grade candidemia. Intensive amphotericin B therapy (mean daily dose: 0.7 mg/kg) in all patients, combined with 5-fluorocytosine in five cases, resulted in cure and long-term survival in six patients who received 1600 to 3435 mg (mean: 26 mg/kg) total dose. None of these patients developed renal failure, while four showed improving renal function during treatment. In contrast to Candida endocarditis, septic central vein thrombosis caused by Candida appears to be curable medically in the majority of cases with intensive amphotericin B therapy (total dose: greater than or equal to 22 mg/kg), combined when feasible with 5-fluorocytosine.     

Gentamicin-induced hypomagnesemia

There have been several case reports of hypomagnesemia associated with gentamicin therapy. A cause and effect relationship between gentamicin and hypomagnesemia has been difficult to establish in these cases due to: 1) large doses of gentamicin; 2) concomitant administration of other antibiotics and cytotoxic agents; 3) failure to monitor drug levels; and 4) poor oral intake. To test for a direct cause and effect relationship and to determine the frequency of gentamicin-induced hypomagnesemia, we administered the drug for 10 days to six healthy, well-fed, subhuman primates. Five of the six animals developed a mean decrease in serum magnesium of 0.34 mg/dl (P = 0.03) after 10 days of therapy. Four of the five had levels in the frankly hypomagnesemic range (less than 1.4 mg/dl). Urine magnesium values were inappropriately elevated in relation to serum magnesium concentrations. It is concluded that gentamicin-induced hypomagnesemia may occur more commonly than has been previously appreciated. Serial monitoring of serum magnesium in patients receiving gentamicin is recommended.     

Decompressive colonoscopy with intracolonic vancomycin administration for the treatment of severe pseudomembranous colitis

Background: We explored the potential of early decompressive colonoscopy with intracolonic vancomycin administration as an adjunctive therapy for severe pseudomembranous Clostridium difficile colitis with ileus and toxic megacolon. Methods: We reviewed the symptoms, signs, laboratory tests, radiographic findings, and outcomes from the medical records of seven patients who experienced eight episodes of severe pseudomembranous colitis with ileus and toxic megacolon. All seven patients underwent decompressive colonoscopy with intracolonic perfusion of vancomycin. Results: Fever, abdominal pain, diarrhea, abdominal distention, and tenderness were present in all patients. Five of seven patients were comatose, obtunded, or confused, and six of the seven required ventilatory support. The white blood cell count was greater than 16,000 in seven cases (six patients). Colonoscopy showed left-side pseudomembranous colitis in one patient, right-side colitis in one patient, and diffuse pseudomembranous pancolitis in five patients. Two patients were discharged with improvement. Five patients had numerous medical problems leading to their death. Complete resolution of pseudomembranous colitis occurred in four patients. One patient had a partial response, and two patients failed therapy. Conclusion: Colonoscopic decompression and intracolonic vancomycin administration in the management of severe, acute, pseudomembranous colitis associated with ileus and toxic megacolon is feasible, safe, and effective in approximately 57% to 71% of cases. apd: 7 May 2001     

Cefazolin as empiric therapy in hemodialysis-related infections: efficacy and blood concentrations

Concern about the increasing incidence of vancomycin-resistant organisms has tempered the enthusiasm for indiscriminate vancomycin use. Cefazolin has an antibacterial activity profile similar to vancomycin against most pathogens encountered in the hemodialysis (HD) population. We evaluated the clinical efficacy and serum concentrations that were achieved during empiric cefazolin use. Fifteen consecutive HD patients (five, conventional HD; five, high-efficiency HD; and five, high-flux HD) with suspected or documented infections warranting antibiotic intervention, including access-related, respiratory tract, urinary tract, or wound infections, were enrolled. Each patient received intravenous cefazolin (20 mg/kg actual body weight rounded to the nearest 500-mg increment [range, 1 to 2 g]) after each dialysis treatment for at least three doses. Cefazolin concentrations were obtained before and immediately after the next three consecutive dialysis treatments. Thirteen patients were evaluated for efficacy and all 15 were evaluated for toxicity and cefazolin blood concentrations. All patients showed at least a short-term (3-week) clinical resolution of infection with cefazolin treatment. No central nervous system toxicities were noted and no other adverse events were expressed by the patients during the course of cefazolin treatment. Predialysis cefazolin concentrations, as determined by high-performance liquid chromatography, were 70.2 +/- 42.7 (conventional HD), 45.6 +/- 18.9 (high-efficiency HD), and 41.6 +/- 23.9 mg/L (high-flux HD) over the three dialysis sessions. Cefazolin at doses of approximately 20 mg/kg administered post-HD appears to be a safe and effective empiric therapy and yields predialysis cefazolin concentrations of 2.5 times or greater than those considered to be the minimum inhibitory concentration breakpoint (16 mg/L) for susceptible organisms. These data support the broader use of cefazolin for empiric treatment in the HD population, allowing vancomycin to be reserved for confirmed resistant organisms.     

Ofloxacin pharmacokinetics in patients on continuous ambulatory peritoneal dialysis

Pharmacokinetics of ofloxacin (OFX) was studied in patients on continuous ambulatory peritoneal dialysis (CAPD) carrying out three exchanges per day. In 11 patients given 300 mg of OFX orally, serum OFX concentration peaked at 2.44 mg/l 3.7 hours after administration and the mean elimination half-life of OFX was 25 hours. OFX concentrations in peritoneal fluid underwent cyclical changes with each change of solutions, reaching beyond 0.5 mg/l after 2 hours of equilibration. There was a highly significant correlation between corresponding serum and peritoneal fluid concentrations of OFX after an 8 h equilibration (r = 0.85, p less than 0.001). In 5 patients given a 400 mg loading dose followed by 200 mg of OFX per day for 7 days, trough serum OFX concentrations ranged from 1.35 to 7.00 mg/l and no adverse effects were noticed. CAPD per exchange removed less than 2% of the total dose of OFX given.     

Comparative study of cefaclor and amoxicillin in treatment of urinary tract infection.

Cefaclor or amoxicillin was given to 51 randomly assigned patients with urinary tract infections. Inclusion in the study required two pretreatment urine cultures yielding the same organism (susceptible to both antibiotics) in concentrations greater than or equal to 10(5)/ml. Both drugs were administered as 250 mg. orally every eight hours for ten days. Cefaclor was given to 27 patients and amoxicillin to 24. Most patients in both groups had negative urine cultures at five to nine days and four to six weeks following therapy. One patient in each group was unsuccessfully treated. Relapse or reinfection occurred with similar frequency in both treatment groups. Both antibiotics were well tolerated. minimal inhibiting concentrations (MICS) of cefaclor, amoxicillin, cephradine, and cephalexin were determined by an agar dilution technique for the 44 available pretreatment isolates (41 Escherichia coli and 3 Proteus mirabilis). Mean MICs (micrograms./ml., +/- SD) were 2.2 +/- 1.4 for cefaclor, 4.4 +/- 2.0 with amoxicillin, 8.1 +/- 4.2 for cephradine, and 5.7 +/- 3.0 with cephalexin. Cefaclor is highly active in vitro against those gram-negative bacteria which are commonly isolated from urine. Cefaclor is as effective as amoxicillin when administered three times daily for the treatment of urinary tract infection.     

Ajustement de la posologie de la vancomycine administrée en perfusion continue chez des patients de réanimation

Introduction

As the susceptibility of staphylococcal strains to glycopeptides rises, it is becoming necessary to increase vancomycin dosages.

Objective

To evaluate an administration protocol for vancomycin using continuous infusion with a loading dose of 30 mg/kg followed by 30 mg/kg per 24 h in intensive care patients presenting creatinine clearance (CLc) greater than 50.

Results

A total of 22 patients were included in the study. Serum vancomycin concentrations after 24 h (C24h) ranged from 25 to 30 mg/l in seven of 14 patients with CLc less than 120 ml/min (50 %), compared with three patients (21 %) with C24h greater than 35 mg/l and four patients (29 %) with C24h less than 25 mg/l. However, C24h was less than 20 mg/l for the eight patients with CLc greater or equal to 120 ml/min. Bacteriological data was available for eight of the 14 patients with CLc less than 120 ml/min, and in these eight patients, the C24h/MIC was greater or equal to 8; seven of these patients had an AUC/MIC greater or equal to 350.

Conclusion

Assay of serum vancomycin concentrations after 24 h of treatment is necessary to enable rapid adjustment of vancomycin concentration in order to improve therapeutic efficacy or avoid nephrotoxicity.     

Electroencephalographic activity and serum and cerebrospinal fluid pentobarbital levels in determining the therapeutic end point during barbiturate coma

Controversy exists regarding the optimal means for monitoring the patient receiving pentobarbital therapy during medical coma. Serum pentobarbital levels have been used traditionally to gauge cerebral penetration and efficacy of the drug. These peripheral levels have been assumed to reflect pentobarbital concentrations in the cerebrospinal fluid (CSF) and, therefore, the physiological effect on the central nervous system. To determine the relative accuracy of serum versus CSF pentobarbital levels, continuous electroencephalographic (EEG) monitoring in 10 consecutive patients was studied prospectively. Each patient received pentobarbital therapy for cerebral protection in the face of a traumatic injury. Simultaneous serum and CSF pentobarbital levels were obtained 1) before and after the initial barbiturate bolus, 2) every 12 hours during constant infusion therapy, and 3) before and after subsequent boluses necessary because of elevated intracranial pressure (ICP) (ICP greater than 15 mm Hg) or loss of burst suppression by continuous EEG monitoring (defined as greater than five bursts per minute). ICP and relevant clinical events were recorded hourly. Serum and CSF levels ranged from 33 to 74 mg/L and 4 to 54 mg/L, respectively. There was poor correlation between serum and CSF pentobarbital levels at any given time, although patients remained in burst suppression 73% of the time during their therapy. The EEG monitoring not only provided dynamic physiological monitoring, but it also permitted the lowest pentobarbital dose to maintain burst suppression for a specific patient's metabolism, reducing the likelihood of toxicity. In conclusion, CSF pentobarbital levels are of no greater accuracy than serum pentobarbital levels in predicting physiological effect.(ABSTRACT TRUNCATED AT 250 WORDS)     

Randomized, prospective trial of cimetidine and ranitidine for control of intragastric pH in the critically ill

Forty-eight critically ill patients in an intensive care unit were enrolled in a prospective study of stress ulcer prophylaxis. The H2-receptor antagonists cimetidine and ranitidine were used, patients being randomized on hospital number. Response was assessed by measuring gastric pH every 2 hours. The drugs were administered by intravenous infusion, and up to three dosage increments fo each of the drugs were titrated against the pH of the aspirated gastric juice. If one drug, in maximum dose, failed to maintain the pH above 4, the other drug was administered at maximum dose. If both drugs failed to achieve control of gastric pH, antacids were administered in an endeavor to ensure patient safety. Cimetidine was successful in maintaining the intragastric pH above 4, for the duration of the intensive care admission, in five of 28 patients. Ranitidine was successful in 10 of 20 patients. The difference between these two groups was statistically significant (p = 0.04). In patients in whom cimetidine therapy failed, ranitidine provided adequate control of pH in four of 13. Cimetidine controlled one of six patients who had failed to improve with ranitidine therapy. Plasma concentrations of both drugs were well above established acid inhibitory concentrations. However, even with much lower plasma concentrations of ranitidine, similar amounts of both drugs were present in the gastric juice, suggesting a possible explanation for the greater efficacy of ranitidine. We conclude that, although ranitidine is more effective than cimetidine, neither of these drugs is adequate for stress ulcer prophylaxis. If they ae used for this purpose in the critically ill patient, regular monitoring of gastric pH is essential to allow detection of therapeutic failures.     

Antimicrobial utilisation in 37 Australian and New Zealand intensive care units

This multi-centre point prevalence study reports on antimicrobial dosing patterns, including dose, mode of administration and type of infection, in 37 Australian and New Zealand intensive care units. Of 422 patients admitted to an intensive care unit on 8 May 2007, 195 patients (46%) received antimicrobial treatment, 123 patients (29%) received no antimicrobials and 104 patients (25%) received prophylactic antimicrobials only. Dosing data were available for 331 antimicrobials used to treat 225 infections in 193 patients. Respiratory (40%), abdominal (13%) and blood stream (12%) infections were most common. For adult patients, ticarcillin/clavulanate (23% or 40/177), meropenem (20% or 35/177) and vancomycin (18% or 32/177) were the most frequently used antibiotics; vancomycin was most commonly used in children (31% or 5/16). The majority of antimicrobials were administered as bolus doses or infusions of less than two hours (98% or 317/323); only six patients received extended or continuous infusions. The mode of administration was unknown in eight cases (4.1%). The total defined daily dose for adult patients receiving antimicrobial therapy was 2051 defined daily doses per 1000 patient days. Our results confirm that the use of continuous infusions remains rare, despite increased interest in continuous infusions for time-dependent antibiotics.     

Measurement of vancomycin hydrochloride concentration in the exudate from wounds receiving negative pressure wound therapy: a pilot study

It has been reported that negative pressure wound therapy (NPWT) is effective in the treatment of contaminated wounds. We hypothesised that systemically administered antibiotics migrate to wound site effectively by NPWT, which provides the antibacterial effect. We measured and compared the concentrations of vancomycin in the exudate and blood serum. Eight patients with skin ulcers or skin defect wounds who were treated with NPWT and were administered an intravenous drip of vancomycin were enrolled in this study. The wound surfaces were muscle, muscle fascia or adipose tissue. We administered vancomycin intravenously to NPWT patients (1–3 g/day). The exudate was obtained using 500 ml V.A.C. ATS^® canisters without gel. Three days later, the concentrations of vancomycin were measured. The mean concentration of vancomycin in the exudate from NPWT was 67% of the serum vancomycin concentration. We found that concentrations of vancomycin in NPWT exudates are higher than the previously reported concentrations in soft tissue without NPWT. The proactive use of NPWT might be considered in cases of suspected wound contamination when a systemic antibiotic is administered.     

Once weekly intraperitoneal therapy for gram-positive peritonitis

The pharmacokinetics and clinical outcome following a 30 mg/kg/2 L intraperitoneal (IP) dose of vancomycin, which was administered once a week for 3 weeks, was studied in ten continuous ambulatory peritoneal dialysis patients with peritonitis. Vancomycin was 91% absorbed following the first dose and rapidly achieved therapeutic serum concentrations, 19 +/- 8 mcg/mL at 1 hour and a peak of 37 +/- 8 mcg/mL at 6 hours. Vancomycin was eliminated slowly with a mean total clearance of 7 +/- 3 mL/min/70 kg and a distribution volume of 1.2 +/- 0.3 L/kg. The resultant mean serum t1/2 over the first week was 184 hours and the mean serum concentration at 168 hours was 10 +/- 4 mcg/mL. Based on the positive clinical outcome (100% cure) among patients with uncomplicated gram-positive peritonitis, the potential use of this alternative vancomycin dosing regimen is proposed.