Reducing HAIs and ARIs: partnering with clinical labs.

Many of the most insidious of healthcare-associated (or hospital-acquired) infections (HAIs)--and antibiotic-resistant infections (ARIs)--are creatures of our own unintelligent design. Methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and a growing number of other pathogens developing resistance to many antibiotics are directly attributable to the overuse and misuse of these drugs. For example, 75% of antibiotics are prescribed for acute respiratory-tract infections, despite the fact that approximately 80% of them are of viral origin.

In just over a decade, S aureus, once described as a "controllable nuisance," has evolved into MRSA, one of the fastest-growing resistant infections that does not respond to most antibiotics. In the United States, current MRSA rates exceed 50% (1) of all S aureus infections and stand at nearly 90% in some Asian countries. (2) Lack of compliance with hand-disinfection procedures, inappropriate use of antimicrobials, and underlying diseases prior to hospitalization are some of the most common ways MRSA is spread. In the past five years, MRSA has exploded in the general community--an alarming and ominous trend.

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In 1993, there were fewer than 2,000 MRSA infections in U.S. hospitals. By 2005, the figure had shot up to 368,000, according to the Agency for Healthcare Research and Quality. At Morton Plant Hospital, we now see HAIs almost every day. It is estimated that about 70% of bacteria that cause infections in hospitals are resistant to at least one of the drugs most commonly used to treat infections.

Those who track the genetic shift and drift that makes these pathogens so adaptable believe that VRE poses the next serious health threat. Unfortunately, these scientists believe that the organism has transferred a key antibiotic-resistance gene to Staphylococcus. We are also seeing more cases of Klebsiella pneumoniae Carbapenemase- (KPC-) producing organisms, such as Escherichia coli and Salmonella. KPC pathogens are virtually impervious to all penicillins, cephalosporins, carbapenems, and axteonam, which leaves us with no available treatment.

MRSA plus H1N1 influenza A a threat

At the Second World HAI Forum held in last month in the Les Pensieres Conference Center in Veyrier-du-Lac, France, these supercharged microorganisms were discussed by experts from around the globe, gathered to anticipate what their next move will be. These experts focused on two looming threats.

The first is the convergence of MRSA and H1N1 influenza A. When combined with MRSA, even mild seasonal flu can become very dangerous. The virus distracts the immune system, which has a more difficult time battling the bacterial infection that can lead to severe pneumonia. A 50% mortality rate has been reported with community-acquired MRSA pneumonia. (2) This has already been seen in Australia, which is coming to the end of its flu season. Fortunately, these cases were not common; however, when they did occur, they were frequently fatal. The extent of the problem in the Northern Hemisphere will be determined by the severity of the H1N1 pandemic and the efficacy of the vaccine.

The second looming threat identified at the recent World HAI Forum are bacteria that produce extended spectrum beta-lactamase, or ESBL. This enzyme has evolved the ability to render many antibiotics useless. ESBLs are produced by E coli and K pneumoniae, which are becoming more pervasive and difficult to treat in the hospital setting. In fact, K pneumoniae Carbapenemase can inactivate nearly all antibiotics, including carbapenems, which had been the medical "weapon of last resort."

Resistance enzymes that bypass extended spectrum cephalosporin and carbapenem antibiotics are known as carbapenemases. These molecules have versatile hydrolytic capacities that inactivate antibiotics in the penicillin, cephalosporin, monobactam, and carbapenem families.

Still, doctors perpetuate the problem by increasing the prescription of carbapenems due to the spread of pathogens armed with these resistance enzymes, thereby inadvertently creating carbapenemase-producing bacteria resistant to the antibiotic.

The cost of antibiotic-resistant infections

One of the central battlegrounds in the efforts to overcome antibiotic resistance is the human lung, which is the primary point of entry for many of these pathogens. Each year, 235 million doses of antibiotics are prescribed, but between 20% to 50% of these prescriptions are unnecessary. (3), (4) Of the 41 million antibiotic prescriptions written in the United States each year for respiratory infections, as many 22.5 million (55%) are likely to have been prescribed for non-bacterial infections. (5) One way to dramatically reduce overuse of antibiotics is to avoid treating viral infections and simple inflammation, as in the cases of asthma and chronic obstructive pulmonary diseases (COPD) with antibiotics that do no good.

Two recent studies demonstrate both the impact of this promiscuous use of antibiotics and the benefits that can be realized if we "kick this habit." Researchers at the Cook County Hospital in Chicago published research this month on the true cost of antibiotic-resistant infections. (6) They concluded that the healthcare costs associated with ARIs in that hospital in 2000 ranged between $18,000 to $29,000 per patient, and these patients remained hospitalized for an additional 6.4 to 12.7 days in order to have these infections treated. These patients were more than twice as likely to die than comparable patients who did not become infected with antibiotic-resistant organisms. This study was one of the first to also look at the societal costs of ARIs--those costs borne by the patients and their families--resulting from lost wages or, in the fatal cases, lost income. The researchers calculated that this cost ranged between $10.7 and $15 million for the 188 ARI patient-study population.

Clearly, as healthcare professionals debate the best way to reform our healthcare system, taking steps to avoid ARIs and these monumental treatment and societal costs should be at the top of our list. In September, Schuetz, et al, published a study showing that antibiotic usage can be safely avoided or minimized using a new diagnostic tool to measure levels of procalcitonin, or PCT. (7) Schuetz and his colleagues at six tertiary-care centers in Switzerland used PCT levels to determine the etiology of lower respiratory-tract infections (LRTIs) in more than 1,300 patients and used that information to guide antibiotic treatment, including if and when to start treatment and when to safely stop treatment. Prescription rates and overall antibiotic exposure were significantly reduced in the PCT group for the whole patient population as well as for each LRTI subgroup. The duration of antibiotic exposure was less in the PCT group, with the overall reduction in duration due to the PCT guidance ranging from 25.7% to 38.7% in the six study sites. The adverse effects associated with antibiotics such as nausea, diarrhea, and rash occurred less frequently in the PCT group.

Measurement                    Level of bacterial infection

< 0.05 ng/mL PCT               Normal

0.1 ng/mLto 0.25 ng/mL PCT     Bacterial infection unlikely

< 0.25 ng/mL to 0.5 ng/mL PCT  Bacterial infection possible; Advise
                               start of antibiotics

> 0.5 ng/mL to 0.5 ng/mL PCT   Bacterial infection possible; Advise
                               start of antibiotics

> 0.5 ng/mL PCT                Bacterial infection highly likely
                               Strongly suggest start of antibiotics

The clinical lab is a vital partner in battling ARIs

Morton Plant Mease Health Care in Clearwater, FL, includes four hospitals and a free-standing emergency room. At the Morton Plant Mease critical-care department, personnel have worked closely with clinical lab staff to form a proactive approach to find and apply new technology and clinical practices with the goal of improving outcomes based on a overarching commitment to enhance antibiotic stewardship and reduce ARIs.

Physicians working closely with Morton Plant Mease's laboratory director have developed a program to reduce the use of antibiotics based on the PCT test to help rule out LRTIs; suspected sepsis; asthma and COPD flare-ups that are not caused by bacterial infections--as well as using a sterile lavage protocol that helps rule out contamination in cases of suspected ventilator-associated pneumonias (VAPs).

Procalcitonin

PCT, the pro-hormone of calcitonin, was discovered to be a sensitive biomarker for systemic bacterial infections about 15 years ago. (8) In response to bacterial infections, nearly all tissues in the body release PCT, especially the lungs. (9) In Europe, PCT is commonly used to determine a bacterial-infection immune response from viral infections or an inflammatory response not linked to a pathogen. (10) The "SEPSIS ALERT" protocol was started as a pilot study last year, and hospital staff is in the process of applying the protocol to all of the Morton Plant Mease facilities with the intent to measure the impact on patient care and antibiotic usage. In the Morton Plant Mease laboratory, the chart on page 14 indicates either the lack of or the level of bacterial infection.

PCT is used in the emergency department (ED) to test those admitted patients suspected of having a significant bacterial infection. ED protocol calls for an admitted patient with suspected pneumonia, LRTI, or sepsis, to have three PCT tests performed in the first 12 hours.

PCT typically spikes within the first 12 hours of systemic bacterial infection. If the patient starts improving, we perform the PCT test on that patient every other day. A PCT score on the decline indicates that we arc treating the patient appropriately and that score often allows us to end antibiotic treatment once we know the patient is safe. When PCT continues to increase over a 24-hour to 48-hour period, this is a strong indication, according to our program, that we are not treating the patient appropriately.

Sterile lavage for suspected VAPs

The number of cases of hospital-associated pneumonia is overwhelming, in terms of incidence, mortalities, and treatment costs. A related area of critical concern is improving the accuracy of cultures in patients with suspected VAP. As with PCT, a proactive lab like that at Morton Plant Mease is vital to reducing antibiotic overuse. When we examine patients in our hospital's intensive care unit (ICU) who are on ventilators and see early signs of VAP, our standard response would be to perform a bronchial washing and send it to the lab for culture. Invariably, these cultures were positive because contamination from the endotracheal, or ET, tube is almost unavoidable. The cultures show an organism that may or may not be the cause of the infection. In fact, there may be no infection at all. This then prompts antibiotic usage that may or may not be warranted. This problem is common in ICUs across the country.

If the washing is taken from the lung by sending an aliquot of saline down the endotracheal tube, then sucking it back and culturing the specimen, the specimen is often contaminated by the endotracheal tube colonizer.

At our hospital, we implemented sterile lavage to get a sterile sample by passing a catheter through the intratracheal tube within a protective catheter through the endotracheal tube within the proactive sleeve, which we push deep into the lung. By extracting a washing in that area under these conditions, contamination can be avoided.

The microbiology laboratory scientist then does a quantitative culture--a more accurate way to measure for an infection. If we see 104 organisms per cubic centimeters per milliliter, this indicates a serious situation which is treated aggressively. If, however, the count is less than that, the urgency is significantly decreased since the organism may be a contaminant. Thus, we then have the time to monitor the patient in order to make sure that there is a true infection before we treat. (11), (12)

This change in the VAP protocol--designed by the laboratory staff who were essential to its implementation--has been successful, based on the results. Not only can the laboratory staff lead in the effort to mitigate HAIs by pushing new policies and protocols but also by educating its clinical colleagues. Laboratory personnel can remind doctors and pharmacists of this at every given opportunity. We are all partners in patient care.

By identifying resistance, the lab can help clinicians get clear actionable information, so they can begin effective antibiotic therapy as early as possible. The lab is critical to monitoring resistance with surveillance campaigns of antimicrobial resistance patterns within the hospital, and more broadly in the community. The lab can also play the pivotal role in tracking resistance by screening patients and healthcare workers for multidrug-resistant organisms.

Devendra Amin, MD, F(CCP), is the medical director of Critical Care Services at Morton Plant Hospital in Clearwater, FL.

Note: This article is followed by another article, "Real-time PCR testing for CDI," that is also part of the Continuing Education test.

References

(1.) Centers for Disease Control and Prevention. S, aureus and MRSA Surveillance Summary 2007. http://www.cdc.gov/ncidod/dhqp/ar_mrsa_surveillanceFS.html. Accessed September 21, 2009.

(2.) Science Media Centre. Experts comment on new research regarding Community-Acquired MRSA and pneumonia, as published in The Lancet Infectious Diseases, http://www.sciencemediacentre.org/pages/press_releases/09-05-20_lancet_camrsa.htm. Published May 20, 2009. Accessed September 21, 2009.

(3.) Centers for Disease Control and Prevention, 2000, NEJM. December 28, 2000.

(4.) Christ-Crain M, Jaccard-Stolz D, Bingisser R, Genday MM, et al. Effect of PCT-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised single-blinded intervention trial. Lancet. 2004;363:600-607.

(5.) Gonzales R, Malone DC, et al. Excessive antibiotic use for acute respiratory infections in the United States. Clin Infect Dis. 2001; 33:757-762.

(6.) Roberts RR, Hota B, Ahmad I, Scott DS II, et al. Hospital and Societal Costs of Antimicrobial Resistant Infections in a Chicago Teaching Hospital: Implications for Antibiotic Stewardship. Clin Infect Dis. 2009;(10). http://www.journals.uchicago.edu/doi/abs/10.1086/605630?prevSearch=%2528Roberts%2529%2B AND%2B%255Bjournal%253A%2Bcid%255D&searchHistoryKey=. Accessed September 23, 2009.

(7.) SchuetzP, et al. Effect of Procalcitonin-Based Guidelines vs. Standard Guidelines on Antibiotic Use in Lower Respiratory Tract Infections: The ProHOSP Randomized Controlled Trial. JAMA. 2009;302(10):1059-1066.

(8.) Assicot M, et al. High serum procalcitonin concentrations in patients with sepsis and infection. Lancet. 1993;341:515-518.

(9.) Muller B, et al. Ubiquitous expression of the calcitonin-l gene in multiple tissues in response to sepsis. J Clin Endocrinol Metab. 2001;86:396-404.

(10.) Eberhard OK, et al. Usefulness of procalcitonin for differentiation between activity of systemic autoimmune disease (systemic lupus erythematosus or systemic anti-neutrophil cytoplasmic antibody-associated vasculitis) and invasive bacterial infection. Arthritis Rheum. 1997;40:1250-1256.

(11.) Zahar J-R, Cerf C, Maitre B, Brun-Buisson C, et al. Contribution of Blinded, Protected Quantitative Specimens to the Diagnostic and Therapeutic Management of Ventilator-Associated Pneumonia. Chest. 2005;128;533-544.

(12.) Guidelines for the Management of Adults with Hospital-acquired, Ventilator associated, and Healthcare-associated Pneumonia. This official statement of the American Thoracic Society and the Infectious Diseases Society of America was approved by the ATS Board of Directors, December 2004 and the IDSA Guideline Committee, October 2004. Am J Respir Crit Care Med. 2005;171:388-416.

CONTINUING EDUCATION

To earn CEUs, see current test on pp. 22-23, or at www.mlo-online.com under the CE Tests tab. The October 2009 CE test covers both articles in this section.

LEARNING OBJECTIVES

Upon completion of this article, the reader will be able to:

1. Identify organisms that commonly cause HAIs and ARIs, including Clostridium difficile-associated infection (CDI).

2. Name mechanisms for the increases in HAIs, ARIs, and CDI.

3. Name trends in HAIs, ARIs, and CDI.

4. Name types of infections that put patients at greater risk of fatality from HAIs and ARIs.

5. Describe procedures to reduce the number of HAIs, ARIs, and CDI.

6. Understand testing methods for HAIs, ARIs, and CDI.

By Devendra Amin, MD, F(CCP)