Robert MacLaren

Nosocomial Infections Due to Multidrug‐Resistant Pseudomonas aeruginosa: Epidemiology and Treatment Options

Pseudomonas aeruginosa is one of the leading gram‐negative organisms associated with nosocomial infections. The increasing frequency of multi‐drug‐resistant Pseudomonas aeruginosa (MDRPA) strains is concerning as efficacious antimicrobial options are severely limited. By searching MEDLINE from January 1966–February 2005 and relevant journals for abstracts, we reviewed the frequency, risk factors, and patient outcomes of MDRPA nosocomial infections in critically ill patients, determined the available antimicrobial therapies, and then provided recommendations for clinicians. The definition of MDRPA was established as isolates intermediate or resistant to at least three drugs in the following classes: β‐lactams, carbapenems, aminoglycosides, and fluoroquinolones. Reported rates of MDRPA varied from 0.6–32% according to geographic location and type of surveillance study. Risk factors for MDRPA infection included prolonged hospitalization, exposure to antimicrobial therapy, and immunocompromised states such as human immunodeficiency virus infection. Emergence of MDRPA isolates during therapy was reported in 27–72% of patients with initially susceptible P. aeruginosa isolates. Patients with severe MDRPA infections should be treated with combination therapy, consisting of an antipseudomonal β‐lactam with an aminoglycoside or fluoroquinolone rather than aminoglycoside and fluoroquinolone combinations, to provide adequate therapy and improve patient outcomes. Synergy has been observed when resistant antipseudomonal drugs were combined in vitro against MDRPA with successful clinical application reported in two centers. Colistin with adjunctive therapy, such as a β‐lactam or rifampin, may be a useful agent in MDRPA when antimicrobial options are limited, but patients should be monitored closely for toxicities associated with this agent. Standardization of terminology for MDRPA isolates is needed for consistency and comparability of surveillance and institutional reports. Clinical studies are needed to identify risk factors for MDRPA development and to determine the economic impact of these infections, as well as to determine the most efficacious antimicrobial regimens and duration of therapy to maximize outcomes in the treatment of MDRPA infections.

National Surveillance of Antimicrobial Resistance in Pseudomonas aeruginosa Isolates Obtained from Intensive Care Unit Patients from 1993 to 2002

ABSTRACT Nosocomial infections caused by Pseudomonas aeruginosa in critically ill patients are often difficult to treat due to resistance to multiple antimicrobials. The purpose of this study was to evaluate antimicrobial resistance among P. aeruginosa isolates from intensive care unit patients in the United States from 1993 to 2002 by using the Intensive Care Unit Surveillance Study database. Over the 10-year period, susceptibility of 13,999 nonduplicate isolates of P. aeruginosa was analyzed. From 1993 to 2002, nationwide increases in antimicrobial resistance were greatest for ciprofloxacin, imipenem, tobramycin, and aztreonam. Rates of multidrug resistance (resistance to ≥3 of the following drugs: ceftazidime, ciprofloxacin, tobramycin, and imipenem) increased from 4% in 1993 to 14% in 2002. The lowest dual resistance rates were observed between aminoglycosides or fluoroquinolones with piperacillin-tazobactam while the highest were for those that included β-lactams and ciprofloxacin. Ongoing surveillance studies are crucial in monitoring antimicrobial susceptibility patterns and selecting empirical treatment regimens.

Clinical and economic outcomes of involving pharmacists in the direct care of critically ill patients with infections

Objective:To determine whether the absence or presence of clinical pharmacists in intensive care units (ICUs) results in differences in mortality rates, length of ICU stay, and ICU charges for Medicare patients with nosocomial-acquired infections, community-acquired infections, and sepsis. Design, Setting, and Patients:The type and level of pharmacy services provided to ICUs were obtained from a 2004 national survey. Clinical pharmacy services were defined as having at least a partial pharmacist full-time equivalent specifically devoted to the ICU for the purpose of direct involvement in patient care. Infections were defined using International Classification of Diseases, Ninth Revision, Clinical Modification codes. ICU outcome data were drawn from the 2004 modified Medicare provider analysis and review. Depending on the infection studied, the involvement of clinical pharmacists was evaluated in 8,927–54,042 patients from 265 to 276 hospitals. Interventions:None. Measurements and Main Outcomes:Mortality rates, length of ICU stay, Medicare charges, drug charges, and laboratory charges for each of the infections categorized according to the absence or presence of clinical pharmacists. Compared to ICUs with clinical pharmacists, mortality rates in ICUs that did not have clinical pharmacists were higher by 23.6% (p < 0.001, 386 extra deaths), 16.2% (p = 0.008, 74 extra deaths), and 4.8% (p = 0.008, 211 extra deaths) for nosocomial-acquired infections, community-acquired infections, and sepsis, respectively. Similarly, ICU length of stay was longer by 7.9% (p < 0.001, 14,248 extra days), 5.9% (p = 0.03, 2855 extra days), and 8.1% (p < 0.001, 19,215 extra days) for nosocomial-acquired infections, community-acquired infections, and sepsis, respectively. ICUs that did not have clinical pharmacists had greater total Medicare billings of 12% (p < 0.001,

Sequential single doses of cisapride, erythromycin, and metoclopramide in critically ill patients intolerant to enteral nutrition: A randomized, placebo-controlled, crossover study

132,978,807 extra billing charges), 11.9% (p < 0.001,

A Prospective Evaluation of Empiric versus Protocol‐Based Sedation and Analgesia

32,240,378 extra billing charges), and 12.9% (p < 0.001,

Erythromycin vs Metoclopramide for Facilitating Gastric Emptying and Tolerance to Intragastric Nutrition in Critically Ill Patients

224,694,784 extra billing charges) for nosocomial-acquired infections, community-acquired infections, and sepsis, respectively. Similar findings were observed for Medicare drug charges and laboratory charges. Conclusion:The involvement of clinical pharmacists in the care of critically ill Medicare patients with infections is associated with improved clinical and economic outcomes. Hospitals should consider employing clinical ICU pharmacists.

Gastric Motility Function in Critically Ill Patients Tolerant vs Intolerant to Gastric Nutrition

Objective: To evaluate the comparative efficacy of enteral cisapride, metoclopramide, erythromycin, and placebo for promoting gastric emptying in critically ill patients with intolerance to gastric enteral nutrition (EN). Design: A randomized, crossover study. Setting: Adult medical intensive care unit at a university‐affiliated private hospital and trauma intensive care unit at a university teaching hospital. Patients: Ten adult, critically ill, mechanically ventilated patients not tolerating a fiber‐containing EN product defined as a single aspirated gastric residual volume >150 mL or two aspirated gastric residual volumes >120 mL during a 12‐hr period. Interventions: Patients received 10 mg of cisapride, 200 mg of erythromycin ethylsuccinate, 10 mg of metoclopramide, and placebo as 20 mL of sterile water every 12 hrs over 48 hrs. Acetaminophen solution (1000 mg) was administered concurrently. Gastric residual volumes were assessed, and plasma acetaminophen concentrations were serially determined by TDx between 0 and 12 hrs to evaluate gastric emptying. Measurements and Main Results: Gastric residual volumes during the study were not significantly different between agents. No differences in area under the concentration vs. time curve or elimination rate constant were identified between agents. Metoclopramide and cisapride had a significantly shorter mean residence time of absorption than erythromycin (6.3 ± 4.5 [SEM] mins and 10.9 ± 5.8 vs. 30.1 ± 4.5 mins, respectively [p < .05]). Metoclopramide (9.7 ± 15.3 mins) had a significantly shorter time to peak concentration compared with erythromycin and placebo (60.7 ± 8.1 and 50.9 ± 13.5 mins, respectively [p < .05]). The time to onset of absorption was significantly shorter for metoclopramide vs. cisapride (5.7 ± 4.5 vs. 22.9 ± 5.7 mins [p < .05]). Conclusion: In critically ill patients intolerant to EN, single enteral doses of metoclopramide or cisapride are effective for promoting gastric emptying in critically ill patients with gastric motility dysfunction. Additionally, metoclopramide may provide a quicker onset than cisapride.

A multicenter assessment of recombinant factor VIIa off-label usage: clinical experiences and associated outcomes.

Study Objective. To compare empiric and protocol‐based therapies of sedation and analgesia in terms of pharmacologic cost, effects on mechanical ventilation and intensive care unit (ICU) stay, and quality of sedation and analgesia.

Proton-Pump Inhibitors for Stress Ulcer Prophylaxis in Critically Ill Patients

BACKGROUND The purpose of this study is to evaluate erythromycin vs metoclopramide for facilitating gastric emptying and tolerance to intragastric enteral nutrition (EN). METHODS Twenty critically ill patients with a gastric residual >150 mL while receiving EN were randomized to receive 4 intravenous doses of erythromycin 250 mg or metoclopramide 10 mg, each administered every 6 hours. Acetaminophen 975 mg was administered enterally at baseline and after the fourth dose. Acetaminophen peak plasma concentration (Cmax), concentration at 60 minutes (C(60)), time to Cmax (Tmax), and area under the concentration-time curve from 0 to 60 minutes (AUC(0-60)) were determined. Residual volumes and feeding rates were recorded. RESULTS Compared with baseline, erythromycin increased Cmax (9.5 +/- 6.1 mg/L to 17.7 +/- 11.9 mg/L, P < .01), C(60) (5.4 +/- 3.5 mg/L to 12.9 +/- 7.6 mg/L, P < .01), and AUC(0-60) (3.5 +/- 3.0 mg.h/L to 12.5 +/- 8.7 mg.h/L, P < .01), while metoclopramide increased only AUC(0-60) (4.4 +/- 2.8 mg.h/L to 9.5 +/- 3.8 mg.hr/L, P < .05). Neither agent significantly reduced Tmax. Both erythromycin and metoclopramide reduced residual volumes (122 +/- 48 mL to 36 +/- 48 mL, P < .01, and 103 +/- 88 mL to 21 +/- 23 mL, P < .05, respectively) and allowed increased feeding rates (17 +/- 23 mL/h to 45 +/- 21 mL/h, P < .05, and 14 +/- 17 mL/h to 44 +/- 22 mL/h, P < .05, respectively). CONCLUSIONS Both agents facilitate tolerance to intragastric EN, but erythromycin may be more effective than metoclopramide for enhancing gastric motility.

Recommendations for the role of extracorporeal treatments in the management of acute methanol poisoning: a systematic review and consensus statement.

BACKGROUND Administration of gastric enteral nutrition (EN) in the intensive care unit (ICU) is commonly impeded by high gastric residual volumes (GRV). This study evaluated gastric emptying in patients with limited GRV (tolerant group) vs volumes > or =150 mL (intolerant group) and whether prokinetic therapy improves gastric motility in intolerant patients. METHODS To assess gastric motility, mechanically ventilated patients received acetaminophen 975 mg, and peak plasma concentration (Cmax), concentration at 60 minutes (C(60)), time to Cmax (Tmax), and area under the concentration-time curve from 0 to 60 minutes (AUC(0-60)) were determined. This evaluation was repeated in intolerant patients after 24 hours of either erythromycin 250 mg or metoclopramide 10 mg therapy, both administered intravenously every 6 hours. RESULTS Ten tolerant and 20 intolerant patients were studied. Tolerant patients had significantly greater Cmax (14.12 +/- 7.25 vs 9.28 +/- 5.22 mg/L; p < .05), C(60) (9.62 +/- 4.65 vs 6.08 +/- 4.00 mg/L; p < .001), and AUC(0-60) (10.01 +/- 5.97 vs 3.93 +/- 2.84 mg/h/L; p < .01) and shortened Tmax (0.81 +/- 0.61 vs 1.98 +/- 1.26 hours; p < .001) compared with intolerant patients. After prokinetic therapy, Cmax (15.26 +/- 8.85 mg/L), C(60) (11.96 +/- 5.99 mg/L), and AUC(0-60) (10.90 +/- 6.57 mg/h/L) increased and Tmax (1.07 +/- 1.01 hours) decreased in the intolerant group to values similar to the tolerant group. CONCLUSIONS ICU patients with elevated GRV during gastric EN have delayed gastric motility. Initiating prokinetic therapy accelerates gastric emptying to resemble that of ICU patients tolerating EN.