Bob Roehr

October 11, 2007

October 11, 2007 (San Diego) — Three sets of treatment guidelines that are in the process of being revised and updated were previewed here at the Infectious Diseases Society of America 45th Annual Meeting. They are expected to be finalized and published in early 2008.

Clostridium difficile Infection

Diagnosis: Testing should only be performed on diarrhea (unformed) stools unless ileus resulting from C difficile is suspected. It is not clinically useful for test of cure. The cell cytotoxic assay is the preferred diagnostic, because the enzyme immunoassays for toxins A and B are faster but less sensitive, and newer methodologies such as polymerase chain reaction are not ready for routine use.

Infection Control: Emphasis should be placed on hand hygiene, with the understanding that soap and water are superior to alcohol-based agents. Patients with C difficile infection (CDI) should be isolated to the greatest extent possible; where a separate room is not feasible, patients should be more than 3 feet apart, privacy curtains should be drawn to decrease direct contact, and staff and visitors should use gloves and gowns.

Routine screening of asymptomatic patients is not recommended. Antibiotic use should be minimized to avoid corollary damage to beneficial gut flora that helps to contain growth of C difficile. There are insufficient data to make a recommendation on the use of probiotics for prevention.

Treatment: Avoid antiperistaltic agents; there is little evidence to support their efficacy. Metronidazole, 500 mg 3 times per day, is recommended for mild to moderate CDI. Oral vancomycin, 125 mg 4 times per day, is recommended for initial treatment of severe, uncomplicated CDI. There is no evidence to support combination therapy in uncomplicated CDI.

Severe and complicated CDI should be treated with high-dose vancomycin, 500 mg 4 times per day, and/or metronidazole, 500 to 750 mg every 8 hours. A total or subtotal colectomy should be performed before serum lactate is more than 5.

Metronidazole should not be used beyond first recurrence or longer than 14 days. Second and further use of oral vancomycin should use a tapered regimen.

Antimicrobial Agents in Neutropenic Patients With Cancer

A major proposed change in the guidelines for the use of antimicrobial agents in neutropenic patients with cancer is stratification of patients into high- and low-risk categories, with the development of definitions to assess that risk and guide treatment by risk category.

Definitions: A high-risk patient is defined as one with neutropenia that is anticipated to extend beyond 7 days; with medical comorbidities that include hemodynamic instability; oral or gastrointestinal mucositis–dysphagia/diarrhea; abdominal or perirectal pain; nausea/vomiting; diarrhea (≥6 loose stools daily); neurologic/mental status changes; intravascular–catheter infection; new pulmonary infiltrate, hypoxemia, or underlying chronic obstructive pulmonary disease; hepatic insufficiency (aminotransferase values >5 times normal); and renal insufficiency (creatinine clearance <30 mL/min).

A low-risk patient is one in whom neutropenia is expected to resolve within 7 days, with the absence of comorbidities listed in the high-risk criteria, and with adequate hepatic and renal function.

Evaluation: Initial evaluation should be with 2 sets of blood culture, ideally from both the periphery and catheter, or both from the periphery if no catheter is in place. Drawing both samples from the catheter is not standard of care. Other sites should be cultured when appropriate, and respiratory and liver functions should be evaluated.

Treatment: High-risk patients should be treated with monotherapy of an intravenous antipseudomonal beta-lactam (cefepime, ceftazidime, meropenem, imipenem, or piperacillin-tazobactam). An aminoglycocide, fluoroquinolone, and/or vancomycin may be added for management of complicated cases or if antimicrobial resistance is suspected or proven.

Low-risk patients may be given the same intravenous regimens as high-risk patients. They also have the option of an oral regimen of ciprofloxacin + amoxicillin/clavulanate. Patients with an allergy to penicillin may receive levofloxacin, moxifloxacin, ciprofloxacin + azithromycin, or ciprofloxacin + clindamycin.

High-risk patients who have a continuing or recrudescent fever after 4 to 7 days of therapy should receive empiric antifungal therapy. Amphotericin B desoxycholate is the historic drug of choice; caspofungin, liposomal ampho B, itraconazole, and voriconazole also are acceptable therapies.

Colony-stimulating factors have not been demonstrated to be useful adjuncts to empiric antibiotics.

Immunization of Infants, Children, Adolescents, and Adults

The IDSA last issued practice guidelines in this area in 2002. A handful of new vaccines as well as expanded recommendations for use have subsequently become available. William Schaffner, MD, professor and chairman of the department of preventive medicine at Vanderbilt University School of Medicine, Nashville, Tennessee, reviewed those developments and label indications on behalf of the committee, which he chairs. Revised guidelines will be forthcoming in the spring.

Infectious Diseases Society of America 45th Annual Meeting: Abstracts 1165, 1166, 1167. Presented October 6, 2007.

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