Rose Jung

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.

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

OBJECTIVE: To evaluate the use of proton-pump inhibitors (PPIs) for stress ulcer prophylaxis in critically ill adults. DATA SOURCES: Computerized biomedical literature search of MEDLINE (1966–June 2002) was conducted using the MeSH headings proton-pump inhibitor, ulcer, critical care, and acid. References of selected articles were reviewed. A manual search of critical care, surgery, trauma, gastrointestinal, and pharmacy journals was conducted to identify relevant abstracts. DATA SYNTHESIS: Traditional medications used for stress ulcer prophylaxis include antacids, histamine2 receptor antagonists (H2RAs), and sucralfate. Few studies have evaluated PPIs for stress ulcer prophylaxis. The majority of studies have demonstrated that enteral or intravenous administration of PPIs to critically ill patients elevates intragastric pH and consistently maintains pH ≥4.0. PPIs are safe and seem to be as efficacious as H2RAs or sucralfate for prevention of bleeding from stress-related mucosal damage (SRMD) and they may provide cost minimization. The small patient populations limit the results of comparative studies. CONCLUSIONS: Available data indicate that PPIs are safe and efficacious for elevating intragastric pH in critically ill patients. PPIs should be used only as an alternative to H2RAs or sucralfate since the superiority of PPIs over these agents for preventing SRMD-associated gastrointestinal bleeding has not been established. Additional comparative studies with adequate patient numbers and pharmacoeconomic analyses are needed before PPIs are considered the agents of choice for stress ulcer prophylaxis.

Evaluation of Diagnostic Tests and Argatroban or Lepirudin Therapy in Patients with Suspected Heparin-Induced Thrombocytopenia

Study Objective. To evaluate diagnostic tests for heparin‐induced thrombocytopenia (HIT), a serious drug reaction that can occur in patients receiving heparin, and to evaluate treatment with direct thrombin inhibitors—the only initial drug therapy that decreases the risk of thromboembolism associated with immune‐mediated HIT.

The role of vasopressin in vasodilatory septic shock

Septic shock that requires therapy with adrenergic agents is associated with high rates of mortality. Inappropriately normal or low serum concentrations of vasopressin contribute to the development of hypotension during sepsis. We critically evaluated the role of administering exogenous vasopressin to patients with septic shock. A computerized search of MEDLINE from January 1966–December 2003 and a manual search of relevant journals for abstracts were conducted. Eleven retrospective, six prospective cohort, and four prospective randomized studies were identified. Most studies evaluated short‐term infusions of vasopressin at 0.08 U/minute or less as add‐on therapy in patients requiring adrenergic agents. The results show that starting vasopressin in patients with septic shock increases systemic vascular resistance and arterial blood pressure, thus reducing the dosage requirements of adrenergic agents. These effects are rapid and sustained. Substantial enhancement of urine production, likely due to increased glomerular filtration rate, was shown in several studies. A few studies demonstrated clinically significant reduced cardiac output or cardiac index after vasopressin was begun, necessitating cautious use in patients with cardiac dysfunction. Vasopressin was associated with ischemia of the mesenteric mucosa, skin, and myocardium; elevated hepatic transaminase and bilirubin concentrations; hyponatremia; and thrombocytopenia. Limiting the dosage to 0.03 U/minute or less may minimize the development of these adverse effects. Vasopressin 0.03 U/minute or less should be considered if response to one or two adrenergic agents is inadequate or as a method to reduce the dosage of adrenergic agents. At present, vasopressin therapy should not be started as first‐line therapy. Additional studies are needed to determine the optimum dosage, duration, and place in therapy of vasopressin relative to adrenergic agents. A multicenter, comparative study of vasopressin 0.03 U/minute as add‐on therapy is under way and should provide mortality data.

Effects of Continuous Vasopressin Infusion in Patients with Septic Shock

BACKGROUND: Small studies have reported that vasopressin improves hemodynamic instability in patients with septic shock. OBJECTIVE: To determine whether vasopressin infusion increases blood pressure, decreases catecholamine vasopressor use, and improves renal function in a large patient population with septic shock when used in a clinical setting. METHODS: A retrospective chart audit was conducted of critically ill patients who received vasopressin infusion for septic shock from January 2000 through September 2002. Demographic, hemodynamic, laboratory, vasopressor, and adverse event data were collected. Statistical methods included ANOVA with Tukeys test for post hoc analysis. RESULTS: A total of 102 of 353 patients met study criteria. The mean ± SD vasopressin dosage regimen was 0.11 ± 0.17 units/min for 53.8 ± 71.5 hours. Compared with baseline, vasopressin infusion improved mean arterial pressure (MAP) by 15% within one hour (p < 0.05), reduced heart rate by 9% within 4 hours (p < 0.05), and reduced hourly dopamine dosage by 25% within 8 hours (p < 0.05). These effects persisted through 96 hours. Other hemodynamic variables and catecholamine vasopressor usage parameters were not statistically different from baseline. Urine output, serum creatinine, and serum sodium concentrations were not statistically changed from baseline. Adverse events possibly associated with vasopressin infusion included ischemic digits/extremities, myocardial infarction, and hyponatremia. CONCLUSIONS: Vasopressin infusion was effective in increasing MAP and reducing heart rate while decreasing the dopamine dosage in patients with septic shock. Comparative studies with catecholamine vasopressors are needed to define the optimal role of vasopressin in septic shock therapy. In the meantime, vasopressin infusion at ≤0.03 units/min should be considered only if response to 1 or 2 catecholamine vasopressors is inadequate or as a method to reduce the dose of these therapies.

Stress-Dose Corticosteroid Therapy for Sepsis and Acute Lung Injury or Acute Respiratory Distress Syndrome in Critically Ill Adults

Sepsis and acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) are associated with high mortality rates despite recent therapeutic advances. Both disease states involve uncontrolled host defense responses that lead to inflammation, endothelial damage, enhanced coagulation, diminished fibrinolysis and fibroproliferation to produce microthrombi, and relative adrenal insufficiency. Corticosteroids inhibit the host defense response and may offer an inexpensive therapeutic option. Results of several randomized, double‐blind studies demonstrated no survival benefit and higher secondary infection rates when supraphysiologic doses of corticosteroids were administered for less than 24 hours. Recently, the emphasis of research for corticosteroid therapy has involved adrenocortical replacement dosage regimens administered for several days to weeks, with doses corresponding to the stress level of the disease. Stress‐dose therapy with hydrocortisone in patients with septic shock who require vasopressor support, especially if adrenal insufficiency is present, accelerates hemodynamic stability and reduces mortality. The frequency of gastrointestinal hemorrhage was higher with corticosteroid therapy than with placebo, but the occurrence of secondary infections was similar to that of placebo. The only randomized, double‐blind study that evaluated stress‐dose methylprednisolone therapy for ARDS was terminated early after only 24 patients were enrolled because therapy with methylprednisolone was associated with enhanced survival despite higher secondary infection rates. A multicenter study investigating stress‐dose methylprednisolone for ARDS is under way and should provide valuable information. Sufficient data support stress‐dose hydrocortisone therapy for vasopressor‐dependent septic shock. Stress‐dose methylprednisolone therapy for ALI‐ARDS requires further study but may be warranted in cases of refractory infection‐induced ARDS when impending mortality is likely.

In vitro synergy testing of levofloxacin, ofloxacin, and ciprofloxacin in combination with aztreonam, ceftazidime, or piperacillin against Pseudomonas aeruginosa

The synergistic potential of levofloxacin, ofloxacin and ciprofloxacin combined with aztreonam, ceftazidime, or piperacillin was compared using 24 strains of Pseudomonas aeruginosa with varying susceptibility profiles. Levofloxacin and ciprofloxacin demonstrated similar in vitro activity, with ofloxacin demonstrating less activity compared to the other agents. Predominantly additive effects were seen with all combinations, with no significant differences detected between the fluoroquinolone agents.

A Risk-Benefit Assessment of Levofloxacin in Respiratory, Skin and Skin Structure, and Urinary Tract Infections

As a class, the quinolone antibacterials can no longer be assumed to be both effective and relatively free of significant adverse effects. Recent safety issues with newer generation fluoroquinolones, and concerns regarding drug-use associated bacterial resistance have made all drugs in this class subject to intense scrutiny and further study. Levofloxacin is a second generation fluoroquinolone with a post marketing history of well tolerated and successful use in a variety of clinical situations.Quinolones as a class cause a variety of adverse effects, including phototoxicity, seizures and other CNS disturbances, tendonitis and arthropathies, gastrointestinal effects, nephrotoxicity, prolonged QTc interval and torsade de pointes, hypo- or hyperglycaemia, and hypersensitivity reactions. Levofloxacin has been involved in only a few case reports of adverse events, which include QTc prolongation, seizures, glucose disturbances, and tendonitis.Levofloxacin has been shown to be effective at dosages of 250mg to 500mg once-daily in clinical trials in the management of acute maxillary sinusitis, acute bacterial exacerbations of chronic bronchitis, community-acquired pneumonia, skin and skin structure infections, and urinary tract infections. There are data suggesting that levofloxacin may promote fluoroquinolone resistance among the Streptococcus pneumoniae, and that clinical failures may result from this therapy. Other data suggest that fluoroquinolones with lower potency against Pseudomonas aeruginosa than ciprofloxacin, such as levofloxacin, may drive class-wide resistance to this pathogen.Levofloxacin is an effective drug in many clinical situations, but its cost is significantly higher than amoxicillin, erythromycin, or first and second generation cefalosporins. Because of the propensity to select for fluoroquinolone resistance in the pneumococcus and potentially other pathogens, levofloxacin should be an alternative agent rather than a drug-of-choice in routine community-acquired respiratory tract, urinary tract, and skin or skin structure infections. In areas with increasing pneumococcal β-lactam resistance, levofloxacin may be a reasonable empiric therapy in community-acquired respiratory tract infections. Similarly, in patients with risk factors for infectious complications or poor outcome, levofloxacin may be an excellent empiric choice in severe community-acquired respiratory tract infections, urinary tract infections, complicated skin or skin structure infections, and nosocomial respiratory and urinary tract infections. Better clinical data are needed to identify the true place in therapy of the newer fluoroquinolones in common community-acquired and nosocomial infections. Until then, these agents, including levofloxacin, might best be reserved for complicated infections, infection recurrence, and infections caused by β-lactam or macrolide-resistant pathogens.

Enteral Glutamine Supplementation in Critically Ill Patients with Burn Injuries: A Retrospective Case-Control Evaluation

Study Objectives. To evaluate the clinical application of enteral glutamine supplementation in critically ill patients and compare the frequency of nosocomial infections in these patients with a historical control group in a burn intensive care unit (BICU), and to assess lengths of stay in the hospital and BICU, mortality rates, and safety profile of glutamine.