A Step Forward in Therapy for Hepatitis C

A Step Forward in Therapy for Hepatitis C

Jay H. Hoofnagle, M.D.

The therapy of hepatitis C began almost 25 years ago with a small trial of recombinant human interferon alfa.¹ The rationale for using interferon was its broad antiviral effects and the suspicion that it might be active against the still-undiscovered agent of non-A, non-B hepatitis. Indeed, interferon had striking effects, lowering serum aminotransferase levels and, in a proportion of patients, inducing a lasting improvement in serum enzyme levels. Not until the discovery of the hepatitis C virus (HCV) were the effects of interferon understood; treatment resulted in a decrease in HCV RNA levels, which led to a sustained absence of virus in a proportion of patients.² The difficulty was that interferon required parenteral injections, had multiple adverse effects, and resulted in a poor overall response rate. Nevertheless, interferon was approved for use for hepatitis C treatment in the United States in 1992.

The second important advance in hepatitis C therapy came with the use of ribavirin. Ribavirin is a nucleoside analogue known to have activity against several flaviviruses. When HCV was identified as a flavivirus, ribavirin was an obvious treatment choice. Ribavirin had little effect on serum HCV RNA levels but led to improvements in aminotransferase levels and histologic characteristics of the liver.³ More importantly, when combined with interferon, ribavirin increased the rate of sustained virologic response.⁴ Interferon and ribavirin given in combination for 48 weeks yielded rates of sustained virologic response of 40 to 50%, two to three times those obtained with interferon alone.³ Ribavirin was approved for use as an adjunct to interferon therapy of hepatitis C in 1998.

A third advance in therapy of hepatitis C came soon thereafter, with the introduction of pegylated forms of interferon that allowed for once-weekly (rather than thrice-weekly) injections. Peginterferon yielded higher rates of sustained virologic response than standard interferon: 45 to 55% after a 48-week course of peginterferon and ribavirin.⁵ The response rates varied according to HCV genotype. Among patients infected with genotypes 2 and 3 (approximately 25% of patients in the United States), rates of sustained virologic response were 70 to 80% and were achieved with a 24-week course and reduced doses of ribavirin.⁶ In contrast, rates of sustained virologic response among patients infected with genotype 1 (approximately 70% of patients in the United States) were less satisfactory, ranging from 40 to 50% and requiring 48 weeks of full doses of ribavirin. In some populations, response rates were even lower, with rates of approximately 25 to 30% among blacks.⁷ Higher doses and longer courses of therapy increased rates of sustained virologic response minimally and usually were associated with increased side effects.³ Peginterferon was approved in the United States in 2001.

Almost 10 years later, a fourth advance in hepatitis C therapy is still awaited but now may be close at hand. Two articles in this issue of the Journal describe results of phase 2 trials involving telaprevir (formerly known as VX-950).^8,9 Telaprevir is a specific inhibitor of the HCV protease and is one of several molecules developed according to a rational drug design based on the molecular structure of HCV.¹⁰ Telaprevir is peptidomimetic, meaning that it resembles the HCV polypeptide that is cleaved by the viral protease, a necessary step in replication. However, telaprevir has an electrophilic “serine-trap warhead” that forms a covalent bond with the catalytic serine residue of the protease, blocking its activity. Telaprevir, an agent developed specifically to target HCV, represents a new era of therapy for hepatitis C.

Telaprevir has profound effects on HCV replication in cell culture and in animal models.¹⁰ In phase 1 studies of chronic hepatitis C, a 1-to-2-week course of telaprevir lowered HCV RNA levels by 2 to 5 log₁₀ IU per milliliter.¹¹ As expected, this short-term therapy was followed by a rebound in viral levels after the drug was stopped. Furthermore, telaprevir resistance appeared rapidly, and viral levels trended upward during the last days of treatment. The combination of telaprevir and peginterferon appeared to provide more profound viral suppression and less viral resistance.^12,13 Some patients treated with peginterferon and ribavirin for a full 48 weeks after the short course of therapy with telaprevir, peginterferon, and ribavirin had a sustained virologic response.

These phase 1 studies led to the design of the two trials reported here, by McHutchison et al. in the United States (ClinicalTrials.gov number, NCT00336479 [ClinicalTrials.gov] )⁸ and Hézode et al. in Europe (NCT00372385 [ClinicalTrials.gov] ).⁹ The trial designs were somewhat complex. Telaprevir was given for 12 weeks only, in combination with peginterferon alfa-2a with or without ribavirin, which were given for either for the same 12 weeks or for a total of 24 or 48 weeks. The control group received the standard therapy of peginterferon and ribavirin for 48 weeks. Standard therapy yielded rates of sustained virologic response of 41% and 46%, respectively. In comparison, telaprevir given for 12 weeks combined with peginterferon and ribavirin given for 24 weeks yielded response rates of 61% and 69%, both significant increases over the responses to standard therapy.

The other regimens tested had less satisfactory results. The stopping of all therapy at 12 weeks yielded lower rates of sustained virologic response than seen with continuation of therapy through 24 weeks, and the use of peginterferon and telaprevir without ribavirin was associated with high rates of relapse. Finally, in the study by McHutchison et al., the continuation of peginterferon and ribavirin for a total of 48 weeks, including the initial 12-week course of all three agents, was no more effective than the 24-week regimen (rate of sustained virologic response, 67% and 61%, respectively). These phase 2 trials suggest that the addition of telaprevir to the combination of peginterferon and ribavirin will increase rates of sustained virologic response in patients with chronic hepatitis C due to infection with HCV genotype 1 from approximately 45% to as high as 65% and will permit therapy to be limited to 24 weeks, thus avoiding the expense and side effects of prolonged therapy.

An obvious question is why telaprevir was given for only 12 weeks and not continued with the peginterferon and ribavirin for a total of 24 or 48 weeks. The reason was the side effects. In both studies, telaprevir was associated with an increased rate of anemia, nausea, diarrhea, pruritus, and rash. The rashes tended to be severe, to arise after 8 weeks of treatment, and to increase in frequency thereafter. The nature and cause of the rashes were not elucidated.

A second question is why the rate of sustained virologic response to the combination of telaprevir, peginterferon, and ribavirin was not higher. In preliminary studies, this combination led to decreases of the HCV RNA to undetectable levels within a few weeks in almost all patients.^11,12,13 Nevertheless, at the end of the treatment period in these two trials, only 57% and 70% of patients had undetectable HCV RNA levels, end-of-treatment response rates that can be achieved with the use of peginterferon and ribavirin alone.^5,6,7 Because the relapse rates were lower among patients receiving telaprevir than among those receiving standard therapy, the sustained virologic response rates were higher with telaprevir. Therefore, the enhanced response rates with telaprevir may be due to the prevention of viral breakthrough and relapse and may occur only in patients who have at least a partial response to peginterferon.

Telaprevir appears to be a material advance in the therapy of hepatitis C, beginning a new era of treatment — an era of antiviral agents developed specifically to target this virus. Other HCV-specific agents, including other protease inhibitors,¹⁴ helicase and polymerase inhibitors, and molecular agents that interfere with viral replication,¹⁵ are likely to follow. Combinations of these new agents with drugs currently in use may ultimately provide effective therapy for all patients with hepatitis C, the promised goal of decades of research.

No potential conflict of interest relevant to this article was reported.
Source Information

From the Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD.

References

1. Hoofnagle JH, Mullen KD, Jones DB, et al. Treatment of chronic non-A, non-B hepatitis with recombinant human alpha interferon: a preliminary report. N Engl J Med 1986;315:1575-1578. [Abstract]
2. Hoofnagle JH, Seeff LB. Peginterferon and ribavirin for chronic hepatitis C. N Engl J Med 2006;355:2444-2451. [Free Full Text]
3. Di Bisceglie AM, Conjeevaram HS, Fried MW, et al. Ribavirin as therapy for chronic hepatitis C: a randomized, double-blind, placebo-controlled trial. Ann Intern Med 1995;123:897-903. [Free Full Text]
4. McHutchison JG, Gordon SC, Schiff ER, et al. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. N Engl J Med 1998;339:1485-1492. [Free Full Text]
5. Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002;347:975-982. [Free Full Text]
6. Hadziyannis SJ, Sette H Jr, Morgan TR, et al. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med 2004;140:346-355. [Free Full Text]
7. Conjeevaram HS, Fried MW, Jeffers LJ, et al. Peginterferon and ribavirin treatment in African American and Caucasian American patients with hepatitis C genotype 1. Gastroenterology 2006;131:470-477. [CrossRef][ISI][Medline]
8. McHutchison JG, Everson GT, Gordon SC, et al. Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection. N Engl J Med 2009;360:1827-1838. [Free Full Text]
9. Hézode C, Forestier N, Dusheiko G, et al. Telaprevir and peginterferon with or without ribavirin for chronic HCV infection. N Engl J Med 2009;360:1839-1850. [Free Full Text]
10. Lin K, Perni RB, Kwong AD, Lin C. VX-950, a novel hepatitis C virus (HCV) NS3-4A protease inhibitor, exhibits potent antiviral activities in HCV replicon cells. Antimicrob Agents Chemother 2006;50:1813-1822. [Free Full Text]
11. Reesink HW, Zeuzem S, Weegink CJ, et al. Rapid decline of viral RNA in hepatitis C patients treated with VX-950: a phase Ib, placebo-controlled, randomized study. Gastroenterology 2006;131:997-1002. [CrossRef][ISI][Medline]
12. Forestier N, Reesink HW, Weegink CJ, et al. Antiviral activity of telaprevir (VX-950) and peginterferon alfa-2a in patients with hepatitis C. Hepatology 2007;46:640-648. [CrossRef][ISI][Medline]
13. Lawitz E, Rodriguez-Torres, Muir AJ, et al. Antiviral effects and safety of telaprevir, peginterferon alfa-2a, and ribavirin for 28 days in hepatitis C patients. J Hepatol 2008;49:163-169. [CrossRef][ISI][Medline]
14. Sarrazin C, Rouzier R, Wagner F, et al. SCH 503034, a novel hepatitis C virus protease inhibitor, plus pegylated interferon alpha-2b for genotype 1 nonresponders. Gastroenterology 2007;132:1270-1278. [CrossRef][ISI][Medline]
15. McHutchison JG, Bartenschlager R, Patel K, Pawlotsky J-M. The face of future hepatitis C antiviral drug development: recent biological and virologic advances and their translation to drug development and clinical practice. J Hepatol 2006;44:411-421. [CrossRef][ISI][Medline]

When to Start Antiretroviral Therapy — Ready When You

When to Start Antiretroviral Therapy — Ready When You

Paul E. Sax, M.D., and Lindsey R. Baden, M.D.

The optimal time to start antiretroviral therapy in asymptomatic patients has been one of the central controversies in the care of patients with the human immunodeficiency virus (HIV) since the introduction of the first antiretroviral agent, zidovudine, more than two decades ago.¹ Since then, periods of enthusiasm for aggressive early intervention² have been followed by a more cautious approach.³ This slowly swinging pendulum has been pushed back and forth by the extraordinary benefits of antiretroviral therapy on one side⁴ and emerging data on its adverse effects on the other.⁵

The absence of a controlled, prospective study comparing early and deferred therapy has forced treatment guidelines to rely largely on data from observational cohort studies.^6,7 Currently, these guidelines state that the optimal time to start therapy for an asymptomatic patient with a CD4+ count of more than 350 cells per cubic millimeter is unknown.

In this issue of the Journal, Kitahata and colleagues present data from the one of the largest of these observational cohorts, the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD).⁸ The combined effort of 22 North American prospective research groups, NA-ACCORD evaluated patients with HIV infection who had not undergone previous therapy and who were stratified according to their CD4+ count at baseline: 351 to 500 cells per cubic millimeter or more than 500 cells per cubic millimeter. The investigators compared survival between patients who started antiretroviral therapy within the given CD4+ stratum with those who waited until after the CD4+ count fell below the stratum.

The results are striking. Among the 8362 patients with a CD4+ count of 351 to 500 cells per cubic millimeter, deferral of therapy until the CD4+ count had fallen to 350 cells or less was associated with an increase of 69% in the risk of death, as compared with patients who initiated therapy when their CD4+ count was within the designated range. Similarly, among the 9155 patients with a CD4+ count of more than 500 cells per cubic millimeter, deferral of therapy until the CD4+ count fell below 500 cells was associated with a significantly increased risk of death of 94%.

The strengths of this study included its relatively large size, the use of advanced statistical methods that attempted to analyze the data in a fashion similar to that of a randomized trial, and the use of survival (rather than AIDS progression or death) as the end point. The use of death from any cause is important in evaluating patients who have higher CD4+ counts, since HIV-related opportunistic infections and cancers develop relatively infrequently in such patients.⁹ Indeed, in the NA-ACCORD study, the majority of deaths for which cause was available were from “non–AIDS-defining” causes. An additional strength of the study was its ability to minimize lead-time bias by having access to data for patients before antiretroviral therapy was started. In many other cohort studies, such events are either not accounted for¹⁰ or must be estimated with the use of historical data.¹¹

The strengths of the study notwithstanding, the results of the NA-ACCORD study cannot be considered definitive evidence that everyone with HIV should start receiving antiretroviral therapy. This was not a randomized trial, and the patients who chose to begin therapy early might have differed in other important ways from those who chose to defer therapy — ways that improved survival but were not measured. Although NA-ACCORD investigators tried to account for this potential bias by controlling for known associations with an increased risk of death in patients with HIV infection (e.g., increased rates of coinfection with hepatitis C virus and of injection-drug use), some unmeasured factors inevitably remain. For example, in many ways, patients who were offered and began potent combination antiretroviral therapy with a high CD4+ count in the late 1990s were the ideal patients: highly adherent, committed to doing whatever they could to prevent AIDS, and willing to push through the sometimes punishing side effects and drug-regimen burdens of the early therapies. This sort of “health-seeking” behavior cannot be measured in the NA-ACCORD study yet could still substantially influence outcomes; its effects can be accounted for only in a randomized, prospective study. In addition to differences in baseline factors, such as HCV infection and injection-drug use, the rates of virologic suppression after 12 months of therapy differed between the two groups among patients with a CD4+ count of more than 500 cells per cubic millimeter (81% in the early-therapy group vs. 71% in the deferred-therapy group), which suggests different levels of adherence to therapy.

Some additional limitations should be considered. A relatively high proportion (approximately 45%) of patients in each study-specified stratum of CD4+ counts either did not initiate antiretroviral therapy or did not have a decline in the CD4+ count. These patients are not included in the comparative analysis, and we have no way of knowing whether antiretroviral therapy would have been beneficial in this group. Broader use of antiretroviral agents may increase the incidence of viral resistance. However, since data regarding resistance are unavailable at this time, we do not know how an earlier starting strategy would influence future treatment options. Data on certain toxic effects of antiretroviral therapy (most notably, metabolic and morphologic side effects) are not provided, and potential long-term toxicity cannot be addressed. The causes of death are available for only 16% of the patients who died; it will be important to obtain more complete follow-up on these patients to better understand the deleterious effects of poorly controlled HIV infection on end-organ dysfunction. It also must be determined whether some of the deaths might have been related to underlying differences (including lifestyle choices) between the two nonrandomized study groups.

Finally, the specific therapies that patients underwent reflected an earlier era in HIV therapy (the median year for starting treatment in these patients was 2000), so a high proportion of patients began regimens containing an unboosted protease inhibitor, a strategy that is no longer recommended, in part because of reduced efficacy in patients with more advanced HIV infection. Conversely, one could argue that the results of the NA-ACCORD study are all the more remarkable, given the numerous improvements in treatment since that time.

Even with the above limitations, the NA-ACCORD study adds to a growing body of data supporting earlier treatment for HIV infection. The Strategies for Management of Antiretroviral Therapy (SMART) trial (ClinicalTrials.gov number, NCT00027352 [ClinicalTrials.gov] ) showed that continuous antiretroviral therapy was safer than intermittent antiretroviral therapy; this was true even among patients who had a CD4+ count of more than 350 cells per cubic millimeter but who were not receiving antiretroviral therapy at baseline. Therefore, in some ways, the SMART trial mimicked a study of early versus deferred therapy.¹² Another critical observation of the SMART trial was that non-AIDS complications occurred more commonly in patients in the intermittent-therapy group, which suggests that whatever the side effects of antiretroviral therapy, they were not as deleterious as untreated HIV infection.¹³

Potential additional benefits of earlier therapy for HIV may include a lower rate of drug-specific toxic effects, a greater likelihood of achieving a normal CD4+ count, a reduction in immune activation and inflammation, and a decreased risk of HIV transmission. Analyses of cost-effectiveness have shown that antiretroviral therapy also compares favorably with other widely adopted medical interventions.⁴ Increasing the CD4+ threshold to start therapy at a range of 350 to 500 cells per cubic millimeter would add only a few years of additional therapy onto projected decades of treatment and hence generate a relatively small added lifetime cost. The impending availability of a greater number of generic antiretroviral drugs, including lamivudine in 2010, could further reduce the cost of treatment.

As we learned regarding the use of estrogen in postmenopausal women,¹⁴ we must be cautious in interpreting observational data despite efforts to control for confounding. The NA-ACCORD data do not provide definitive proof that we should be starting antiretroviral therapy in all patients with HIV infection. Such a conclusion would require data from a randomized, prospective clinical trial, and at least three such studies are either ongoing or planned. However, the supportive evidence for the benefits of earlier therapy continues to increase, making strategies to identify patients with HIV infection before the onset of substantial immunodeficiency all the more compelling.¹⁵

Five years ago, if an asymptomatic patient with HIV infection and a CD4+ count of more than 500 cells per cubic millimeter wished to start antiretroviral therapy, most experienced clinicians could have made an excellent case why treatment should be deferred. Today, if a similar patient were eager to start, we should be ready and willing to prescribe therapy — with ongoing careful monitoring of toxic effects that could arise during decades of treatment.

Dr. Sax reports receiving research support from GlaxoSmithKline, Merck, and Tibotec and consulting fees from Abbott, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Merck, Pfizer, and Tibotec. No other potential conflict of interest relevant to this article was reported.
Source Information

From the Division of Infectious Diseases and the Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School — both in Boston.

This article (10.1056/NEJMe0902713) was published at NEJM.org on April 1, 2009.

References

1. Friedland GH. Early treatment for HIV: the time has come. N Engl J Med 1990;322:1000-1002. [ISI][Medline]
2. Ho DD. Time to hit HIV, early and hard. N Engl J Med 1995;333:450-451. [Free Full Text]
3. Henry K. The case for more cautious, patient-focused antiretroviral therapy. Ann Intern Med 2000;132:306-311. [Free Full Text]
4. Walensky RP, Paltiel AD, Losina E, et al. The survival benefits of AIDS treatment in the United States. J Infect Dis 2006;194:11-19. [CrossRef][ISI][Medline]
5. Friis-Moller N, Sabin CA, Weber R, et al. Combination antiretroviral therapy and the risk of myocardial infarction. N Engl J Med 2003;349:1993-2003. [Erratum, N Engl J Med 2004;350:955.] [Free Full Text]
6. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Washington, DC: Department of Health and Human Services, November 3, 2008:1-139. (Available at http://aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL.pdf.)
7. Hammer SM, Eron JJ Jr, Reiss P, et al. Antiretroviral treatment of adult HIV infection: 2008 recommendations of the International AIDS Society-USA panel. JAMA 2008;300:555-570. [Free Full Text]
8. Kitahata MM, Gange SJ, Abraham AG, et al. Effect of early versus deferred antiretroviral therapy for HIV on survival. N Engl J Med 2009;360:1815-1826. [Free Full Text]
9. Baker JV, Peng G, Rapkin J, et al. CD4+ count and risk of non-AIDS diseases following initial treatment for HIV infection. AIDS 2008;22:841-848. [CrossRef][ISI][Medline]
10. Egger M, May M, Chêne G, et al. Prognosis of HIV-1-infected patients starting highly active antiretroviral therapy: a collaborative analysis of prospective studies. Lancet 2002;360:119-129. [Erratum, Lancet 2002;360:1178.] [CrossRef][ISI][Medline]
11. Cole SR, Li R, Anastos K, et al. Accounting for leadtime in cohort studies: evaluating when to initiate HIV therapies. Stat Med 2004;23:3351-3363. [CrossRef][ISI][Medline]
12. Emery S, Neuhaus JA, Phillips AN, et al. Major clinical outcomes in antiretroviral therapy (ART)-naive participants and in those not receiving ART at baseline in the SMART study. J Infect Dis 2008;197:1133-1144. [CrossRef][ISI][Medline]
13. Currier JS, Baden LR. Getting smarter — the toxicity of undertreated HIV infection. N Engl J Med 2006;355:2359-2361. [Free Full Text]
14. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA 2002;288:321-333. [Free Full Text]
15. Branson BM, Handsfield HH, Lampe MA, et al. Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. MMWR Recomm Rep 2006;55:1-17. [Medline]

SHEA 2009: Inappropriate Catheterization Is Common

From Medscape Medical News
SHEA 2009: Inappropriate Catheterization Is Common

Kristina Rebelo

March 24, 2009 (San Diego, California) — Inappropriate urinary catheterization in hospitalized patients is common but should not be used as a remedy for incontinence because it is significantly associated with urinary complaints and increased hospital length of stay, according to a poster presented here at the Society for Healthcare Epidemiology of America (SHEA) 19th Annual Scientific Meeting.

The research said inappropriate use has been identified as 1 of the risk factors for catheter-associated urinary tract infections, primarily the result of indwelling urinary catheters. To date, data on risk factors associated with this inappropriate use have been scarce.

“This study reinforces just how prevalent these devices are in modern hospitals and how frequently their use is unnecessary,” said SHEA president Mark E. Rupp, MD, medical director, healthcare epidemiology/infection control professor, Section of Infectious Diseases, University of Nebraska Medical Center, in Omaha. He is the senior author of the study.

Convenience a Factor

Dr. Rupp told Medscape Infectious Diseases that “the number 1 reason for this is that people become complacent about them and they forget that they’re in. Nurses may leave them in because they’re convenient — nobody likes to change diapers or change bedding. If a patient has incontinence, this is 1 way to prevent them from soiling the bedding, but it puts the patient at risk of developing a urinary tract infection or something more severe, with the infection developing into bacteremia due to catheter-related infection.”

Using electronic-data-capture methods, the University of Nebraska Medical Center researchers conducted a prospective study analyzing the medical records of 391 adult patients admitted to their medical center. Between October and December 2007, a total of 444 urinary-catheter-days were recorded among 123 patients with urinary-catheter use in a medical/surgical-care unit.

Their results indicated that 31.5% of patients had a urinary-catheter device at some point during their hospital stay. The most common indication for Foley-catheter use in this patient group was surgery or postoperative management (75%). Patient age was the only risk factor that was significantly associated with urinary-catheter use (P < .05).

No significant association was found between urinary-catheter use and outcome measures, such as mortality, intensive-care-unit admission, and readmission or culture-order rates. The study did find, however, that urinary-catheter use was significantly associated with urinary complaints, such as urinary frequency, hematuria, fever, and urinary tract infections (P < .05).

Dr. Rupp said that their study wasn’t designed to closely examine outcome measures.

“Presumably, this could contribute to morbidity and mortality, but this was a very small study focused on establishing the extent of inappropriate catheter use and not the complications of that misuse — we looked at 123 patients, but to establish morbidity and mortality, we would need to have looked at literally thousands of episodes,” said Dr. Rupp.

Study results indicated that 38.2% of patients with a urinary catheter had at least 1 day of inappropriate catheter use, and 32.9% of all catheter-days were regarded as unnecessary. Inappropriate catheter use was significantly associated with length of hospital stay and duration of catheterization (P < .05).

Other Methods Available

Dr. Rupp explained there are other ways incontinent patients can be cared for during hospitalization that do not involve the use of a catheter: “Diapers can be used, the patient can perhaps be more frequently reminded to use the restroom, or the urinal [or bedside commode] can be brought to them.”

“There’s even information to indicate that intermittent catheterization is less likely to cause infections than an indwelling catheter,” Dr. Rupp added. “In other words, put someone on a schedule where you insert the tubing several times a day rather than permanently. For men, there’s such a thing as a condom catheter. It fits over the penis using adhesive and collects the urine as it drains, rather than having a tube that goes into the bladder.”

When asked if nurses would be able to make time for patient bladder surveillance, Dr. Rupp said that “they should have time, and if they don’t, that’s an indication that we need to increase our staffing ratios so we have enough people on the wards to care for our patients; we’re working toward trying to establish that.”

New Guidelines on Catheter Placement

Jennifer Meddings, MD, clinical lecturer at the University of Michigan Health System, in Ann Arbor, who presented 2 research posters at SHEA in the same clinical area, said that Dr. Rupp’s conclusions did not surprise her.

“I would have been surprised at a different conclusion. We’ve known about this inappropriate catheter use for decades,” said Dr. Meddings, who mentioned that new guidelines, by the Healthcare InfectionControl Practices Advisory Committee (HICPAC) of the US Centersfor Disease Control and Prevention, for catheter placement intended to provide evidence-based recommendations for preventing catheter-related infections are coming out in a few months.

“The new HICPAC [guidelines] will say that placing these catheters for convenience or incontinence is clearly inappropriate and will not be tolerated,” she said. “Oftentimes, nurses will place catheters on their own without a physician’s order; according to the studies, this happens in different settings in maybe 1 out of 3 cases [because] patients that may have difficulty getting out of bed or staff may not want to change the linens.”

Dr. Meddings said that researchers in the area of catheter-related infections are hoping that the new Medicare regulations, where hospitals will no longer receive high payments for costs associated with treating patients for certain hospital-acquired infections, will cut inappropriate catheter use.

“The number 1 risk factor is prolonged placement and the first way to prevent infection is that patients don’t get it if they don’t need it,” she said.

“We need to look at this from 2 perspectives: first, to minimize placement on the front end — who gets them in the first place; and second, to remove them once they’ve been in place,” Dr. Meddings concluded. “It’s a 2-pronged approach, when it goes in and when it comes out, and we need to look at both problems. Trying to solve 1 problem won’t do it; we need to address both problems in a healthcare setting.”

The study authors and Dr. Meddings have disclosed no relevant financial relationships.

Society for Healthcare Epidemiology of America (SHEA) 19th Annual Scientific Meeting: Poster 138. Presented March 20, 2009.