Journal watch: Recent studies of note

Recent studies about warfarin use during chemotherapy, C. glabrata bloodstream infection, and other topics.


Warfarin may not reduce thrombosis during chemotherapy

Warfarin may not reduce rates of thrombosis in cancer patients receiving chemotherapy, a recent study reported.

Researchers in the United Kingdom performed an open-label randomized trial to determine whether warfarin decreases rates of catheter-related thrombosis in cancer patients with central venous catheters for chemotherapy. The study involved 68 U.K. facilities and 1,590 patients, with a primary outcome of symptomatic catheter-related thrombosis confirmed by radiologic examination. The results appeared in the February 14 Lancet.

The rate of catheter-related thromboses did not differ in 324 patients receiving fixed-dose and adjusted-dose warfarin compared with no warfarin (relative risk, 0.99 [95% CI, 0.57 to 1.72]; P= 0.98), although fixed-dose warfarin performed better than adjusted-dose (relative risk, 0.38 [95% CI, 0.20 to 0.71]; P= 0.002). The warfarin and no warfarin groups did not differ in a combined end point of thromboses and major bleeding or in survival.

Although the number of thrombotic events observed was small, the authors concluded that prophylactic warfarin is not effective for thrombosis prevention in patients with cancer and should no longer be used for this indication in this population. An accompanying editorial agreed in general with this conclusion but noted that clinicians should try to identify high-risk cancer patients in whom thromboprophylaxis might still be useful.

Previous therapy increases chance of resistance in C. glabrata bloodstream infection

Patients previously treated with fluconazole and linezolid have a greater chance of developing fluconazole-resistant health care-associated Candida glabrata bloodstream infection (BSI), a study has found.

Researchers in Philadelphia performed a case-case-control study to identify risk factors for fluconazole-resistant C. glabrata BSI. Patients treated at three hospitals from Jan. 1, 2003 to May 31, 2007 were evaluated. The results appeared in the February 23 Archives of Internal Medicine.

Seventy-six patients with fluconazole-resistant C. glabrata BSI, 68 patients with fluconazole-susceptible C. glabrata BSI, and 512 controls were included in the study. Those who had previously been treated with fluconazole or linezolid were at greater risk for developing fluconazole-resistant infection (adjusted odds ratios [95% CIs], 2.3 [1.3 to 4.2] and 4.6 [2.2 to 9.3], respectively), while those who had received previous treatment with cefepime and metronidazole were more likely to develop fluconazole-susceptible infection (adjusted odds ratios [95% CIs], 2.2 [1.2 to 3.9] and 2.0 [1.1 to 3.5]).

Although this retrospective study had limitations, including its geographic homogeneity, the authors concluded that previous treatment with fluconazole or linezolid is an independent risk factor for fluconazole-resistant health care-associated C. glabrata BSI. They called for additional studies to assess the effect of less fluconazole use on resistance patterns.

Cardiovascular risk factors could predict safety of IV immunoglobulin treatment

Elderly patients' cardiovascular risk burden could predict their likelihood of suffering a thromboembolic event after intravenous (IV) immunoglobulin treatment, a recent study found.

Researchers performed a case-control study to determine whether the presence of cardiovascular risk factors (coronary artery disease, cerebrovascular disease, cigarette use, hypertension, hyperlipidemia and diabetes mellitus) increased risk for thromboembolic events during IV immunoglobulin infusion. The results were published early online March 1 by the Journal of Neurology.

Nineteen elderly patients (mean age, 71 years) who had a thromboembolic event (primarily stroke, but also myocardial infarction, deep venous thrombosis, or pulmonary embolism) within two weeks of immunoglobulin treatment were compared with 38 age-matched control patients who received the same treatment but did not suffer a thromboembolic event. Risk for thromboembolic events was elevated in patients with two or more cardiovascular risk factors (odds ratio, 1.39 [95% CI, 0.45 to 4.30]) and was statistically significantly elevated in patients with four or more cardiovascular risk factors (odds ratio, 10.50 [95% CI, 1.91 to 57.58]). No difference was seen in 30-day mortality between the case and control groups.

The authors acknowledged their study's limitations, including its retrospective design and the wide CIs resulting from the low number of thromboembolic events. They concluded that patients with more cardiovascular risk factors are more likely to have thromboembolic events after IV immunoglobulin treatment, but the degree of increased risk is difficult to predict. They recommended that clinicians prescribing IV immunoglobulin to elderly patients with cardiovascular risk factors carefully consider the risk of stroke and myocardial infarction, and called for future prospective studies to better quantify risk and incidence.

PPIs may weaken the benefits of clopidogrel after ACS

Proton-pump inhibitors (PPIs) combined with clopidogrel after an acute coronary syndrome (ACS) may increase risk of death or readmission, leading some to suggest that the combination not be used for prophylaxis.

PPIs are frequently prescribed to reduce the risk of gastrointestinal tract bleeding from taking clopidogrel and aspirin. But studies have reported that omeprazole decreases clopidogrel's platelet inhibitory effect. Researchers did a retrospective cohort study of 8,205 ACS patients taking clopidogrel after discharge from 127 Veterans Affairs hospitals between Oct. 1, 2003, and Jan. 31, 2006. They reported results in the March 4 Journal of the American Medical Association.

Of the 8,205 patients, 63.9% were prescribed a PPI (60% of which was omeprazole) in addition to clopidogrel at discharge, during follow-up, or both, and 36.1% were prescribed clopidogrel only. Death or rehospitalization for ACS occurred in 29.8% (1,561) of patients taking both medications versus 20.8% (615) of patients taking clopidogrel without PPI. The combination was associated with increased risk of death or rehospitalization for ACS compared with use of clopidogrel only and a higher risk for revascularization procedures, but no higher risk for all-cause mortality. PPI therapy without clopidogrel was not associated with adverse outcomes.

Randomized, controlled trials are needed, researchers wrote, because PPIs are frequently prescribed to patients receiving dual-antiplatelet therapy and the “modest” risk seen in the study therefore translates to a considerable number of people. They added that PPIs should be used only for patients with a clear indication, such as a history of gastrointestinal tract bleeding, rather than for routine prophylaxis.

Combining antibiotics for S. aureus may be nephrotoxic

Adding initial low-dose gentamicin to penicillin or vancomycin for Staphylococcus aureus native-valve endocarditis is nephrotoxic and the drug should not be used routinely, researchers said.

Researchers performed a prospective cohort study of safety data from a randomized, controlled trial of therapy for S. aureus bacteremia and native-valve infective endocarditis among 236 patients in 44 hospitals in four countries. In the study, 116 patients received antistaphylococcal penicillin or vancomycin plus initial low-dose gentamicin. Another 120 received daptomycin monotherapy.

Researchers measured renal adverse events and clinically significant decreased creatinine clearance in patients in the randomized study arms who had received any initial low-dose gentamicin either as a study medication or two or fewer days before enrollment. They reported their results in the March 15 Clinical Infectious Diseases.

Renal adverse events occurred in eight (7%) of 120 daptomycin recipients, 10 (19%) of 53 vancomycin recipients, and 11 (17%) of 63 antistaphylococcal penicillin recipients. Decreased creatinine clearance occurred in nine (8%) of 113 evaluable daptomycin recipients, 10 (22%) of 46 evaluable vancomycin recipients, and 16 (25%) of 63 antistaphylococcal penicillin recipients.

Another 21 patients had received initial low-dose gentamicin two or fewer days before study enrollment. A total of 22% of these patients experienced decreased creatinine clearance compared to 8% of patients who hadn't received the drug (P= 0.005). Even a few days of initial low-dose gentamicin in combination with the other drugs was frequently associated with renal dysfunction.

In an editorial, said infectious disease experts have been ruling out the practice for years, and that the current study puts the issue to rest against using this approach on a routine basis for the patients and drugs investigated in the study.

Topical mupirocin may be most effective for eradicating MRSA

Short-term nasal application of mupirocin is the most effective way to eradicate carriage of methicillin-resistant Staphylococcus aureus (MRSA), according to a recent review.

Dutch researchers performed a systematic review of 23 clinical trials to determine the best method to combat MRSA carriage. Included studies were in English or Dutch, involved human subjects, and evaluated eradication of MRSA, methicillin-susceptible S. aureus (MSSA), or both. The authors assumed that MSSA carriage has a similar response to eradication therapy if agents are used with activity against both MRSA and MSSA, such as was shown with mupirocin. Twelve trials evaluated topical antibiotics, seven trials evaluated systemic antibiotics, and four trials evaluated both. The results appear in the April 1 Clinical Infectious Diseases.

Short-term nasal topical treatment with mupirocin was effective in 94% of carriers (424 of 453) at one week and had an estimated pooled relative risk of failure of 0.10 (range, 0.07 to 0.14). At follow-up of at least two weeks, however, the effectiveness rate fell to 65% (402 of 622 carriers). Rates of mupirocin resistance and related adverse events were low. Treatment with oral antibiotics had estimated pooled relative risks of 0.47 (range, 0.39 to 0.57) at one week and 0.54 (range, 0.33 to 0.87) after longer follow-up. Approximately 9% of patients (39 of 443) developed resistance to oral antibiotics, and no serious adverse events were reported.

The authors determined that short-term treatment with mupirocin applied nasally is the most effective way to eradicate MRSA carriage and recommended its use before surgery to decrease MRSA transmission. However, they wrote, patients at risk for treatment failure, such as those with skin lesions, should receive both systemic and topical drugs.