The Doctor's Channel - Infectious Diseases

Tenofovir-related renal dysfunction can't always be reversed

2010-03-09T16:55:19+00:00

NEW YORK (Reuters Health) - Tenofovir nephrotoxicity can't always be fully reversed in HIV-infected men, according to a new study.

Up to 2% of patients have adverse renal effects from the nucleotide reverse transcriptase inhibitor, and reportedly, kidney function rapidly normalizes when tenofovir is stopped. But "because of the few cases, limited follow-up and the insensitive measure used" (serum creatinine) in the previous reports, it's not known how reversible the nephrotoxicity really is, note senior author Dr. Andrew Carr, from St. Vincent's Hospital, Sydney, Australia, and colleagues.

In a paper published online February 19th in the Journal of Acquired Immune Deficiency Syndromes, Dr. Carr and his associates describe 24 men who discontinued tenofovir because their estimated glomerular filtration rate (eGFR) was less than 60 ml/minute/1.73 m2.

During a median of 30 months between start of tenofovir and drug cessation, median eGFR fell from 74 to 51 ml/min/1.73 m2 - a reduction about 10 times greater than expected with normal aging.

During the median period of 13 months after tenofovir discontinuation, eGFR rose by a median of 19 ml/min/1.73 m2. Most improvement occurred in the first month.

In only 10 (42%) patients did eGFR return to pre-tenofovir levels, and only two exceeded 90 ml/min/1.73 m2.

Twelve patients had eGFR increases above the median; this group had a more rapid monthly decline while on tenofovir compared to those with less improvement (1.9 vs 0.7 ml/min/1.73 m2, p = 0.009) and a shorter duration of tenofovir therapy (21 vs 51 months, p = 0.08), suggesting that "more acute renal damage is less likely to be permanent."

These patients were also more likely to have received protease inhibitors (100% vs 54%, p = 0.02). The authors explain that protease inhibitors can increase tenofovir levels in plasma and renal tubular epithelium. Therefore, the greater improvement was likely due to cessation of higher tenofovir exposure.

The single-center study was retrospective, relatively small and had a variable duration of follow-up, and so prospective validation in a larger, more heterogeneous population is needed, the researchers say.

Nevertheless, they conclude, earlier discontinuation of tenofovir might have led to greater improvements in renal function, "which underlines the importance of regular assessment and perhaps of earlier intervention."

Specifically, they advise, even gradual deterioration in eGFR to levels above 60 ml/min/1.73 m2 might be cause enough to discontinue tenofovir.

Reference:
J Acquir Immune Defic Syndr 2010.

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Cardiac vegetations don't rule out percutaneous ICD lead extraction

2010-03-08T19:26:08+00:00

NEW YORK (Reuters Health) - Percutaneous extraction of pacemaker or implantable cardioverter-defibrillator (ICD) leads is safe in patients with cardiac vegetations, investigators report. And as long as blood cultures remain sterile, permanent devices can be reimplanted within a week or two.

Eradication of device-related infection requires complete system removal, the authors note in the March 2nd Journal of the American College of Cardiology. Traditionally, patients with vegetations larger than 1 cm in diameter have had their leads removed via thoracotomy, in order to avoid septic emboli -- but the surgery itself increases patients' risks for serious complications and for prolonged recovery.

Senior author Dr. Steven P. Kutalek and associates at Drexel University College of Medicine, Philadelphia, studied 100 patients (mean age, 67 years) who had 1838 leads extracted percutaneously despite echocardiographic evidence of vegetations. This group accounted for roughly 10% of all the percutaneous lead extraction cases at the authors' center between 1991 and 2007.

The vegetations ranged from 0.2 to 4.0 cm in largest diameter (mean 1.6 cm). Implants had been in place for an average of 51 months. The median extraction time (4 min per lead) was not significantly different from the median in a reference group consisting of all 66 patients without vegetations who underwent extraction in 2004.

Five patients had complications during lead extraction, including embolized vegetation in two. However, all 5 were discharged in stable condition and recovered uneventfully.

In 54 patients, surgeons reimplanted new devices during the same hospitalization, at a median of 7 days after extraction. None of these second devices had to be extracted due to relapsing infection.

Twenty-nine patients were lost to follow-up. In the remaining 71, the average follow-up was 438 days.

Nineteen patients died - 11 of persistent septicemia, 1 of sudden cardiac death, and the other 7 of unknown causes with no evidence of ongoing infection (including 4 who had received a new device).

Ten patients died within 30 days of lead extraction. "These unfortunate outcomes occurred in a critically ill subset of patients who often have extensive comorbidities," the researchers note. They attribute the operative mortality to disease severity rather than the mode of lead extraction.

Also, "given the frequent ambiguity of initial culture data," the authors recommend transesophageal ultrasonography before device extraction in order to identify patients at high risk for endocarditis.

This study demonstrates that "percutaneous lead extraction with vegetations of all sizes is possible and seemingly appropriate," Dr. James D. Maloney at Heartland Spine and Specialty Hospital, Overland Park, Kansas, and Dr. James D. Maloney III at the University of Wisconsin, Madison, write in a related editorial.

Still, they're concerned that residual infected inflammatory tissue needs to be debrided after the leads are removed.

"The question remains... if a nidus of chronic infection sometimes remains, does that cause refractory sepsis and congestive heart failure?" they ask. "Can and should it be removed surgically?"

Reference:
J Am Coll Cardiol 2010;55:886-897.

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Four clinical factors help rule out bacterial conjunctivitis in kids

2010-03-04T19:12:12+00:00

NEW YORK (Reuters Health) – Four clinical factors can help rule out bacterial conjunctivitis in children, New York City researchers say.

The four factors are: age at least 6 years, only watery discharge (or no discharge), no glued eyes in the morning, and presentation between April and November, according to Dr. James A. Meltzer and colleagues from Jacobi Medical Center in the Bronx.

Children who met all four of these criteria had more than a 90% likelihood of a negative culture for bacterial conjunctivitis, the investigators report in the March issue of the Archives of Pediatrics and Adolescent Medicine.

The researchers say the goal of their study -- which involved 368 patients ages 6 months to 17 years -- was to determine whether a low risk of bacterial conjunctivitis could be predicted based on history and physical examination findings.

They note that up to 80% of the time, conjunctivitis in children is bacterial. But since there are no guidelines to help distinguish bacterial from nonbacterial cases, most clinicians prescribe antibiotics for all cases of acute conjunctivitis, even though “bacterial resistance to antibiotic drugs is an ever-increasing problem, and there is a nationwide effort to find conditions for which antibiotic drug use can be restricted.”

The children in the study had come to the authors’ pediatric emergency department with conjunctival erythema, eye discharge, or both. Any child with eye trauma, chemical exposure, contact lens use, or antibiotic use in the last 5 days was excluded. The study group was 52.7% male and the median age was 3 years.

For each child, the treating clinician completed a checklist of signs and symptoms and collected a conjunctival swab for bacterial culture.

Roughly 35% of subjects had negative conjunctival cultures. Using the researchers’ model, children with none of the specified characteristics had an 11.8% rate of negative cultures, compared to a 76.4% rate in children with three factors and a 92.3% likelihood of negative cultures for children whose eye conditions met all four criteria.

“If these findings are validated in other populations, we may be able to limit routine antibiotic drug administration for children with acute conjunctivitis,” the authors conclude.

Reference:
Arch Pediatr Adolesc Med 2010;164:263-267.

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Treatment of cervical dysplasia doesn’t increase preterm births: study

2010-03-03T16:04:38+00:00

NEW YORK (Reuters Health) – Pregnant women who’ve had abnormal cervical tissue removed with a loop electrosurgical procedure (LEEP) are not at increased risk for preterm delivery, a retrospective study suggests.

The 2006 consensus guidelines for management of cervical intraepithelial neoplasia (CIN) indicate that this procedure does increase the risk for adverse pregnancy outcomes. And the 2009 guideline for cervical cytology screening has cut back and delayed the recommended schedule, partly to avoid unnecessary interventions that could be harmful. (See Reuters Health report of November 20, 2009.)

However, researchers at the University of Texas Southwestern Medical Center in Dallas question whether “characteristics intrinsic to the woman undergoing LEEP might be associated with the adverse pregnancy effects rather than the procedure itself.”

Their study population included 241,701 women, all with singleton pregnancies, who gave birth at Parkland Hospital between 1992 and 2008. Five hundred eleven had LEEP before the index pregnancy and 842 had LEEP after the pregnancy. The mean interval from LEEP to subsequent pregnancy was 113 weeks, but 11% had an interval of no more than 90 days.

Lead author Dr. Claudia L. Werner and co-investigators note that clinicians did not modify prenatal care or surveillance for patients with a history of LEEP.

In the March issue of Obstetrics and Gynecology, the researchers report that the proportion of women delivering at 36 weeks or less was 7% in the general population, 7% among women who had LEEP prior to the pregnancy, and 9% among those who had LEEP after the pregnancy (p = ns). There was also no significant association between LEEP and perinatal mortality.

Recent studies on this topic have had conflicting results, Dr. Werner’s team points out. Two of three meta-analyses published between 2003 and 2008 suggest that LEEP does increase the risk of preterm birth.

The authors note that their study did not include information on potential confounders, such as substance use or prior preterm births, or data on LEEP depth, amount of excised tissue, or the degree of neoplasia.

They conclude, “LEEP cannot definitively be implicated as a cause of preterm birth.”

“I think the risk of premature birth is related more to the reasons that women get abnormal pap smears that lead to LEEP,” Dr. Jay Iams, an obstetrician at Ohio State University in Columbus, told Reuters Health. He explained that LEEP is performed to treat CIN that is often related to sexually transmitted viral infections, such as human papillomavirus. “People with these infections also have an increased risk for preterm birth.”

For women who’ve had any cervical procedure, Dr. Iams provides no extra surveillance other than using “ultrasound to check their cervix once or twice before 22 weeks’ gestation.”

Dr. Alan G. Waxman of the University of New Mexico, Albuquerque, who headed up the committee that developed the 2009 American College of Obstetrics and Gynecology guidelines, told Reuters Health that almost all the literature after 2003 shows an increased risk of preterm birth associated with LEEP.

“That’s why we recommend conservative surveillance for younger women,” he said. “But I’m delighted that Dr. Werner’s group is adding more evidence to what is a growing body of knowledge.”

According to Dr. Waxman, “some studies show that the extent of LEEP makes a difference, especially if it is a centimeter or more in depth,” which may account for the research team’s findings. “There may also be population differences.”

He advises that physicians should “be cognizant that most literature does show increased risk of preterm birth and should take that into account when weighing the risks and benefits of doing excision procedures.”

Reference:
Obstet Gynecol 2010;115:605-608.

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Montelukast cuts recurrent wheezing with RSV bronchiolitis

2010-03-02T20:08:06+00:00

NEW YORK (Reuters Health) - Montelukast (Singulair), a leukotriene receptor antagonist, can help prevent recurrent wheezing episodes after respiratory syncytial virus (RSV) bronchiolitis, new research shows.

From earlier work, the researchers knew that airway levels of cysteinyl leukotriene correlated with eosinophil numbers in RSV bronchiolitis. The goal of the present study was to see if reduction of leukotriene levels with montelukast might reduce eosinophil degranulation, which in turn would help reduce recurrent wheezing.

To this end, Dr. Chang-Keun Kim, from Inje University Sanggye Paik Hospital in Seoul, Korea, and colleagues conducted a randomized trial in 200 infants, 6 to 24 months of age, who were hospitalized with a first episode of acute RSV bronchiolitis. Daily for three months, the babies received either oral montelukast 4 mg or placebo. Eosinophil degranulation was assessed by serum levels of eosinophil-derived neurotoxin.

The researchers report their findings in the February 22nd online issue of the Journal of Pediatrics.

At the end of the treatment period, eosinophil-derived neurotoxin levels had decreased significantly in the montelukast group (p < 0.01) and increased significantly in the placebo group (p < 0.0001), the researchers report. Neurotoxin levels remained significantly lower in the montelukast group at 12 months. (Twelve-month data was available for 79 babies in the treatment group and 71 in the placebo group.)

Infants in the montelukast group had significantly fewer recurrent wheezing episodes (p = 0.039), but the significant difference between the groups only emerged after 9 to 12 months. Although this may not seem like strong supporting evidence for montelukast, the authors note this is likely because of the short observation period.

The results "suggest that eosinophil degranulation is important in the pathogenesis of severe RSV disease and that therapies that inhibit degranulation of eosinophils warrant further investigation," the authors said.

Also, they point out, infants with high levels of eosinophil-derived neurotoxin at 3 months seems to be at increased risk for recurrent wheezing. "Although subsequent wheezing may also be caused by other acute viral infections, we suggest 3-month eosinophil-derived neurotoxin levels may be a useful biomarker for predicting recurrent wheezing in children with post-RSV bronchiolitis," the researchers conclude.

The study was funded, in part, by Merck, the maker of Singulair.

Reference:
J Pediatr 2010.

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Prophylactic antibiotics may cut mortality in burn patients

2010-02-26T17:17:43+00:00

NEW YORK (Reuters Health) – Prophylactic antibiotics may improve survival of burn patients, a meta-analysis suggests, although the authors acknowledge that the quality of the supporting data is weak.

A number of factors increase the risk of infection in burn patients, yet “there is a broad and uniform consensus in the current literature that prophylaxis with systemic antibiotics should not be given to patients with severe burns,” the authors point out.

In their analysis, however, systemic prophylactic antibiotics reduced the odds of in-hospital death by nearly 50%.

In theory, they imply, this finding should not be surprising. “Antibiotic prophylaxis reduces mortality, bacteremia, and ventilator associated pneumonia among patients in intensive care units. Similarities between intensive care and burns patients suggest possibly similar benefit of prophylaxis,” senior author Dr. Mical Paul, from Rabin Medical Center, Tel-Aviv, Israel, and colleagues note.

However, “recommendations for management do not address systemic antibiotic prophylaxis or explicitly state that prophylactic antibiotics are not recommended.”

Reasons cited for not giving prophylactic antibiotics to burns patients include a lack of benefit and an increased risk of adverse events, particularly Clostridium difficile-associated colitis and selection of antibiotic-resistant microbes.

To sort out the benefits and risks of antibiotic prophylaxis in this setting, Dr. Paul’s team conducted a systematic review and meta-analysis of data from 17 randomized or quasi-randomized controlled trials identified through a search of PubMed and other sources. The studies were published between 1966 and 2009 and featured 1113 patients. In each study, a form of prophylaxis—systemic, non-absorbable, or topical—was compared with placebo or no treatment.

“Most trials recruited patients with burns over more than 20% of total body surface area,” the researchers said.

In the February 17th Online First issue of the British Medical Journal, they report that systemic antibiotic prophylaxis, given for 4 to 14 days after admission, cut all-cause in-hospital mortality by 46%. The number needed to treat was 8 and the control event rate was 26%.

By contrast, use of perioperative non-absorbable or topical antibiotics alone did not significantly affect mortality, the researchers found.

Systemic antibiotic prophylaxis appeared to reduce the risk of pneumonia, while perioperative prophylaxis cut the risk of wound infections. Use of anti-staphylococcal antibiotics reduced infection or colonization with Staphylococcus aureus.

In terms of adverse effects, data from three trials indicated a significant increase in resistance to the antibiotic used for prophylaxis.

Still, the authors caution that none of the findings are definitive as the overall methodologic quality of the studies was poor.

“We have shown a discrepancy between current guidelines for management of burns patients recommending against antibiotic prophylaxis and the evidence showing a reduction of about 50% in all cause mortality with systemic antibiotic prophylaxis,” the authors conclude.

“Given the paucity and limitations of the available evidence, this should serve mainly as an urgent call for a large randomized controlled trial,” they add. Moreover, “future trials should assess a full selective decontamination regimen including systemic and non-absorbable antibiotics.”

Reference:
BMJ Online First 2010.

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Treatments for HIV/TB co-infection should start at the same time: study

2010-02-25T19:36:57+00:00

NEW YORK (Reuters Health) - In patients with HIV and tuberculosis (TB) whose CD4 cell counts are below 500/mm3, mortality is increased if antiretroviral therapy is delayed until TB treatment is finished, according to research from South Africa.

TB is the most common opportunistic infection and the most frequent cause of death in HIV-infected patients in developing countries, the authors say. In South Africa, nearly three-quarters of TB patients are co-infected with HIV.

But clinicians often hesitate to treat both diseases at the same time, because of potential drug interactions or overlapping side effects, the immune reconstitution inflammatory syndrome, high pill burden, and “programmatic challenges.”

In the February 25th issue of the New England Journal of Medicine, Dr. Salim S. Abdool Karim, at the University of KwaZulu-Natal, Durban, and colleagues report on their randomized open-label trial comparing simultaneous treatment with delayed antiretroviral treatment. Between 2005 and 2008, the study enrolled 642 co-infected adults with CD4 counts < 500/mm3.

In two integrated-therapy groups, a combined total of 429 patients received antiretroviral therapy starting either within 4 weeks after the initiation of TB therapy or within 4 weeks after the intensive phase of TB therapy (which lasted 2 or 3 months). In a sequential therapy group, 213 patients received HIV treatment only after completion of the 6- to 8-month anti-TB regimen.

TB treatment included rifampin, isoniazid, ethambutol, and pyrazinamide with or without streptomycin. HIV therapy included didanosine, lamivudine, and efavirenz, plus trimethoprim-sulfamethoxazole to protect against opportunistic infections.

On average, patients in the sequential therapy group started antiretroviral therapy 190 days later than those in the integrated-therapy group.

The authors report data up to September 1, 2008, when the data and safety monitoring committee advised that all patients in the sequential-therapy group be started on antiretroviral therapy as soon as possible.

At that point – 2 months after completion of enrollment in the study -- mortality rates per 100 person-years were 5.4 in the integrated therapy group and 12.1 in the sequential-therapy group (adjusted HR 0.43, p = 0.004).

Furthermore, the authors report, “mortality was lower in the integrated-therapy group in all CD4+ count strata.”

Rates of immune reconstitution inflammatory syndrome were 12.4% with integrated therapy and 3.8% with sequential therapy, although there were no related deaths or changes in antiretroviral regimen.

“The paradoxical deterioration in the clinical status is sufficiently common to warrant close clinical monitoring in the first few months after the initiation of antiretroviral therapy in patients co-infected with tuberculosis,” the authors advise.

Rates of other adverse events did not differ between groups.

The investigators acknowledge that they did not determine rates of death due to TB or HIV and that their study included only patients with sputum smears positive for acid-fast bacilli. They can’t make a definitive recommendation as to when antiretroviral therapy should be started during TB therapy until the trial is completed.

Dr. Karim’s group points out that World Health Organization (WHO) guidelines recommend delaying antiretroviral therapy until completion of TB treatment in patients with WHO stage 3 HIV infection and CD4+ counts exceeding 200 cells/mm3.

“Our findings,” they conclude, “suggest that this guideline should be expanded to include cotreatment of HIV infection and tuberculosis in patients with CD4+ counts of less than 500 cells per cubic millimeter.”

In a separate article in the same issue of the journal, researchers suggest that asking patients about three symptoms – cough or fever of any duration or night sweats lasting 3 weeks or more during the previous 4 weeks – can allow clinicians to accurately rule out TB in most HIV-infected patients.

Lead author Dr. Kevin P. Cain, from the U.S. Centers for Disease Control and Prevention, Atlanta, Georgia, and his associates point out that while WHO guidelines call for TB screening when HIV infection is first diagnosed, but there are no evidence-based guidelines for such screening.

Their prospective study – conducted in Southeast Asia -- was designed to develop a clinical algorithm for screening and diagnosis of TB in people with HIV infection in resource-limited settings.

Based on cultured samples of sputum, urine, stool, blood, and lymph-node aspirate (drawn from patients with lymphadenopathy), TB was diagnosed in 267 of 1748 patients (15%; age range 7 to 72 years, median CD4 cell count 242/mm3).

For a cough lasting more than 2 weeks, the sensitivity for TB was only 33%.

Asking patients about cough, fever and drenching night sweats had the highest sensitivity at 93%, with a specificity of 36% and a negative predictive value of 97%.

“This finding may…allow for safe initiation of isoniazid preventive therapy and antiretroviral therapy, if indicated, in people who reported having none of the three predictive symptoms,” the authors suggest.

Sputum smears were positive for fewer than half of patients with TB. The best performing diagnostic approach involved mycobacterial culture, but this modality is impractical in low-resource settings. ]

As a practical middle ground, Dr. Cain’s team points out, “Tuberculosis is relatively uncommon in patients with positive results of symptom screening if they have two negative smears, a normal chest radiograph and a CD4+ cell count of 350 or more per cubic millimeter.”

Reference:
N Engl J Med 2010;362:697-706,707-716.

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Severe sepsis therapy can be guided by lactate clearance

2010-02-25T19:13:31+00:00

NEW YORK (Reuters Health) - During early resuscitation in severe sepsis, lactate clearance can indicate tissue oxygen delivery as effectively as central venous oxygen saturation, with considerably less effort, new research shows.

The guideline recommending use of central venous catheters and computerized spectrophotometry to monitor oxygen saturation in sepsis is based on a single-center study, lead author Dr. Alan E. Jones and associates write in the February 24th Journal of the American Medical Association.

Furthermore, that approach is time-consuming and requires expertise and specialized equipment not always available even in tertiary care emergency departments.

In a prospective, multicenter, noninferiority trial, Dr. Jones, from Carolinas Medical Center, Charlotte, North Carolina, and his colleagues compared the two strategies to as part of an overall attempt to establish goal-directed therapy targets.

Treatment goals were first, to attain a central venous pressure of 8 mm Hg or higher using volume expansion, followed by vasopressors, if necessary, to achieve a mean arterial pressure of 65 mm Hg or higher.

The final goal was to use red blood cells and dobutamine to achieve adequate tissue oxygen delivery. Toward this end, patients were randomized to one of two strategies: (1) attaining a central venous oxygen saturation of at least 70%, or (2) achieving a lactate clearance of at least 10% over 2 hours.

The investigators note that all patients had central lines placed; in the lactate group, “the primary intervention consisted of not connecting the catheter to the computerized…display.”

The study included 300 patients with severe sepsis or septic shock. Emergency room physicians administered assigned treatment until all the treatment goals were achieved or 6 hours had elapsed. Patients were then transferred to the intensive care unit where treatment decisions were left up to the staff.

There were no significant differences between groups in administered treatments, including transfusions and dobutamine, or in protocol-related serious adverse events.

The in-hospital mortality rate was 17% in the lactate clearance group and 23% in the central venous oxygen saturation group, confirming noninferiority between the two treatment goals, according to the authors.

These data, Dr. Jones and his team conclude, “support the substitution of lactate measurements in peripheral venous blood as a safe and efficacious alternative to a computerized spectrophotometry catheter in the resuscitation of sepsis.”

The authors note that “the potential difference in protocol actions directly attributable to using lactate clearance vs (central venous oxygen saturation) was small, because only 10% of patients went on to receive dobutamine or packed red blood cell transfusion.”

In a related editorial, Dr. Roger J. Lewis, from Harbor-UCLA Medical Center in Torrance, California, comments that the study “is an important first step to identifying less burdensome approaches to the initial management of critically ill patients with severe sepsis and septic shock.”

Reference:
JAMA 2010;303:739-746,777-779.

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Postpartum zidovudine/didanosine prevents resistance mutations in HIV

2010-02-23T16:55:46+00:00

NEW YORK (Reuters Health) – Intra-partum nevirapine, given to prevent HIV transmission, contributes to HIV resistance mutations to non-nucleoside reverse-transcriptase inhibitors (NNRTIs) – but a one-month postpartum course of zidovudine plus didanosine helps avoid this problem.

That’s according to results of the multicenter, open-label HIV Prevention and Treatment (PHPT)-4 trial, conducted in Thailand and reported in Clinical Infectious Diseases for March 15.

Third-trimester zidovudine and a single intra-partum dose of nevirapine are used to prevent vertical HIV transmission in resource-limited settings, lead author Dr. Marc Lallemant, from Chiang Mai University, and the study team explain.

Because blood levels of nevirapine remain elevated for weeks following the single dose, this regimen tends to select for NNRTI mutations, decreasing efficacy of subsequent NNRTI-based antiretroviral regimens. The authors theorized that by suppressing viral replication, an additional 1-month postpartum course of zidovudine/didanosine would prevent selection of resistance mutations in mothers.

The trial included 222 HIV-infected pregnant women with CD4 cell counts > 250 cells/mm3 who did not require highly active antiretroviral treatment. Enrollment began in 2005.

The women took 300 mg zidovudine twice daily starting at 28 weeks’ gestation. During labor they received 300 mg zidovudine every 3 hours, plus a single dose of nevirapine 200 mg and didanosine 400 mg. Following delivery, they took zidovudine 200 or 300 mg as well as didanosine 250 or 400 mg once daily for 1 month.

The authors compared NNRTI mutation outcomes with those in 222 women from an earlier trial (2001-2003) who had been treated with antepartum zidovudine and intra-partum nevirapine only. Women in the two trials were matched on CD4 cell count, antepartum zidovudine duration and plasma viral load.

Two different mutation assays, performed within 4 months of delivery, identified new postpartum NNRTI resistance mutations in 4 women (1.8%) in the study group and in 46 controls (20.7%) (p < 0.001), a 91% reduction.

“The 1-month postpartum regimen appeared to be safe, well tolerated, and easy to adhere to,” the investigators report.

They note that preliminary results from another study suggest that a more potent postpartum regimen of lopinavir, zidovudine, and didanosine, of shorter duration, may have similar efficacy.

“Interventions to eliminate post-exposure selection of nevirapine resistance are critical to safeguard a highly efficacious intervention for the prevention of mother-to-child transmission while preserving the mother’s future therapeutic options,” Dr. Lallemant and colleagues conclude.

A commentary by Dr. Mark F. Cotton and associates at Stellenbosch University, Tygerberg, South Africa points out that the study does not answer the question of how to protect HIV-infected infants from developing NNRTI resistance, both from single-dose nevirapine and more prolonged exposure to nevirapine during breast-feeding.

Furthermore, Dr. Cotton and his colleagues add, “This strategy needs to be replicated in Africa, where HIV-1 subtype C has a higher propensity to NNRTI resistance and where women may be sicker.”

Reference:
Clin Infect Dis 2010.

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Probiotic formula prevents diarrhea

2010-02-19T18:49:59+00:00

NEW YORK (Reuters Health) - A commercially available formula of Lactobacillus acidophilus and L. casei prevents Clostridium difficile infection and diarrhea during antibiotic treatment, according to a single-center study from China.

Although meta-analyses indicate that probiotics decrease antibiotic-associated diarrhea, most trials are flawed, senior author Dr. Larry E. Miller and colleagues state. They say that their randomized, double-blind trial is the largest to address these issues and the first to examine dose effects.

The trial included 255 hospital patients, ages 50 to 70, receiving penicillin, cephalosporin or clindamycin. Within 36 hours of starting antibiotic therapy, patients began to take (each day, 2 hours after breakfast) either 2 probiotic capsules (n = 86), 1 probiotic capsule and 1 placebo capsule (n = 85), or 2 placebo capsules (n = 84). All patients were hospitalized for at least 5 days and received antibiotics for at least 3 days (but not more than 14 days). They continued with their assigned treatment for 5 days after finishing the course of antibiotics.

Each probiotic capsule contained 50 billion colony-forming units of L acidophilus CL1285 and L. casei.

As reported online February 9 in the American Journal of Gastroenterology, at 21 days after the end of their assigned treatments, the incidence of antibiotic-associated diarrhea was 44.1% in the placebo group, 28.2% in the 1-capsule group and 15.5% in the 2-capsule group.

Rates of diarrhea due to C. difficile were 23.8%, 9.4%, and 1.2% with placebo, 1 capsule, and 2 capsules, respectively.

The authors estimate that treating five patients at the higher probiotic dose would prevent one case of C. difficile-associated diarrhea.

Overall, the 2-capsule group had the lowest rate of gastrointestinal symptoms, followed by the 1-capsule group. The investigators observed a similar pattern for symptom duration.

They attribute their high response rates to the high probiotic dosage: “The probiotic load of this quantity likely overwhelms the intestinal tract and repopulates the gut with nonpathogenic flora, as well as enhances immune response to inhibit or destroy pathogenic bacteria.”

The researchers note that their findings cannot be generalized to other probiotic products or to younger patients or those of non-Asian descent, and that the effects of probiotic therapy with prolonged antibiotic treatment are unknown.

On the other hand, “this trial used very stringent data collection and data analysis methods…and an intent-to-treat analysis.”

The probiotic capsules used in this study are manufactured by Bio-K+ International (Laval, Quebec, Canada) and marketed as Bio-K+ CL1285. Bio-K+ provided financial support for the trial.

Reference:
Am J Gastroenterol 2010.

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