Synercid

Multidrug-resistant microorganisms continue to threaten our patients. Learn why more new drugs may not be the answer and how you can protect your patient from a potentially devastating infection.

FOR DECADES, we've confidently given patients antibiotics to fight bacterial infections. Over time, however, the widespread use and misuse of antibiotics has encouraged development of microorganisms that resist our usual arsenal of drugs. These multidrug-resistant microorganisms include:

* vancomycin-resistant enterococci (VRE)

* methicillin-resistant Staphylococcus aureus (MRSA)

* vancomycin intermediate S. aureus (VISA)

* vancomycin-resistant S. aureus (VRSA)

* penicillin-resistant Streptococcus pneumoniae

* extended-spectrum beta-lactamase-producing micoorganisms (ESBLs).

By increasing complications, length of hospital stays, and patient-care requirements, infections caused by these dangerous microorganisms jeopardize patients and add significantly to health care costs.

In this article, I'll explain how antibiotic resistance evolved, what you can do to help prevent the spread of multidrug-resistant microorganisms among your patients, and how we may deal with these microorganisms in the future.

Ever-evolving microorganisms

Although antibiotics have improved quality of life and increased life expectancy, they've also given us a false sense of security. Multidrug-resistant Gram-positive and Gram-negative bacteria are the direct result of extensive, and sometimes inappropriate, use of antibiotics in humans and animals.

To understand how multidrug-resistant microorganisms came to be, consider the role of microorganisms in our everyday lives. We share our world with invisible bacteria, fungi, viruses, and parasites. In fact, each human body is home to billions of bacteria.

Under ordinary circumstances, these bacteria are harmless or even beneficial. For example, billions of bacteria inhabit our intestines, digesting nutrients and helping to ward off foodborne pathogens such as Salmonella and Campylobacter. Many bacteria also live peacefully on our skin. But when bacteria move into a normally sterile environment, such as urine, infection can occur.

When a patient takes an antibiotic, it kills not only the infection-causing bacteria, but also other bacteria that are part of his normal flora. For example, when a patient takes antibiotics for a prolonged time, the elimination of some beneficial bacteria in the intestines can result in an overgrowth of Clostndium difficile, causing diarrhea.

Of the 50 million pounds of antibiotics that U.S. pharmaceutical companies produce each year, almost half are used in animal feed to enhance growth. Multidrug-resistant microorganisms that develop in animals are then passed to humans through ingestion of animal products.

A patient infected with a multidrug-resistant microorganism can unknowingly contaminate his environment (bed rails, furniture, toilets, and patient-care equipment). In the hospital, health care workers can easily pick up multidrug-resistant microoganisms on their hands and carry them to other patients, equipment, and treatment areas.

As you read about each multidrug-resistant microorganism, remember that closely following hand hygiene recommendations is the simplest and best way to stop disease transmission. Recent guidelines from the Centers for Disease Control and Prevention (CDC) recommend routine use of alcohol-based hand rubs to decontaminate hands that aren't visibly soiled. You should still wash with soap and water if your hands are visibly soiled or contaminated with body fluid.

Let's take a close look at each type of multidrug-resistant microorganism.

Unrelenting VRE

First reported in the United States in 1996, VRE has even been found on the hands of health care workers after they've washed their hands with regular soap. Because these bacteria survive on the skin, someone carrying VRE may leave it on furniture, doorknobs, and electrocardiograph wires. To kill VRE on your skin, you must use an antiseptic soap that contains chlorhexidine.

The most common species causing VRE infection are Enterococcus faecalis and Enterococcus faecium. Although both species are inherently resistant to the cephalosporins and increasingly resistant to amino-glycosides, both may respond to treatment with linezolid (Zyvox).

The health care provider should use empiric therapy (using antibiotics before the pathogen is identified) only until the pathogen is identified. Once the pathogen is identified, the patient should be switched to a narrow-spectrum antibiotic. Vancomycin is used in patients with life-threatening conditions caused by microorganisms that are resistant to drugs with fewer adverse effects. Use patient isolation, contact precautions, and basic infection control measures to prevent the spread of VRE from patient to patient. For more information on precautions for VRE and MRSA, see "Taking Aim at Antibiotic-Resistant Bacteria" in the November issue of Nursing200I.

MRSA: Making hospital rounds

When penicillin was introduced in the 1940s, virtually every strain of S. aureus was susceptible to it. But by 1950, 60% of all hospital-acquired S. aureus infections were resistant to the drug. The reason? Random strains of S. aureus had developed an enzyme (beta-lactamase) that could destroy the penicillin molecules beta-lactam ring, rendering the drug ineffective.

To fight the newly formed resistant strains, researchers developed new classes of semisynthetic, beta-lactamase-resistant penicillins: oxacillin, nafcillin, and methicillin. But in 1961, a methicillin-resistant strain of S. aureus was reported in Europe; in 1968, it appeared in the United States.

The U.S. strains were resistant to aminoglycosides, erythromycin, tetracycline, and clindamycin. Today, more than 50% of all hospital-acquired S. aureus infections are MRSA. Vancomycin was traditionally used to treat MRSA, but because of VRSA emergence, linezolid or quinupristin/ dalfopristin (Synercid) may be better choices.

Use patient isolation, contact precautions, and basic infection control measures to prevent the spread of MRSA from patient to patient.

VISA: Linked to dialysis

At one time, vancomycin was the gold standard for treating Gram-positive infections, especially MRSA. But in 1997, a strain of S. aureus with reduced susceptibility to vancomycin-VISA-was reported in Japan. Soon after, the same strain appeared in the United States.

As of June 2001, six cases have occurred in the United States and all were found in patients with MRSA who'd received vancomycin. Five of these patients were on hemodialysis and had underlying infections that didn't respond to vancomycin. Dialysis patients may be susceptible because of infected arteriovenous hemodialysis grafts.

To reduce the threat of VISA, prescribers must reduce their use of vancomycin, especially in patients receiving dialysis. Patients infected with VISA may be treated with linezolid or quinupristin/ dalfopristin; however, strains resistant to these drugs have begun to emerge.

To prevent the spread of VISA, use basic infection control measures, including patient isolation and contact precautions (see Caring for a Patient with VISA or VRSA). Learn more about these precautions at the CDC Web site included in Selected Web Sites at the end of this article.

VRSA: Emerging from MRSA

In June 2002, VRSA was reported in an American patient with diabetes, chronic renal failure, and peripheral vascular disease. She'd been treated with vancomycin for chronic foot ulcerations and had also received dialysis at an outpatient dialysis center.

In April 2002, she'd developed MRSA from an infected arteriovenous hemodialysis graft. The graft was removed, and she received antibiotic therapy with vancomycin and rifampin. In June 2002, her temporary dialysis catheter site became infected. One week later, VRSA was isolated from the patient's chronic foot ulcer.

Fortunately, this infection was susceptible to other antibiotics. The patient was successfully treated with systemic trimethoprim/ sulfamethoxazole and aggressive wound care.

The CDC confirmed that the isolate not only contained the gene for MRSA (mecA) but also contained the vancomycin-resistance gene vanA, which is found in VRE. Knowing that both VRE and MRSA had been present in the wound, researchers concluded that the vanA gene had been transferred from VRE into MRSA, creating VRSA.

The dialysis center promptly put special infection control procedures recommended by the CDC into place, and no other occurrences were reported at that dialysis center. However, a second case occurred at a dialysis center in another state. Consequently, health care workers must be familiar with care precautions for patients with VRSA. Because VRSA has recently emerged, treatment is on a case-by-case basis.

Pinpointing penicillin-resistant S. pneumoniae

Although we usually associate S. pneumoniae with community-acquired pneumonia (CAP) in adults and acute otitis media (AOM) in children, it can also cause meningitis, sinusitis, bacterial bronchitis, and conjunctivitis in patients of any age.

In 1990, penicillin (or ampicillin) was the drug of choice for CAP caused by S. pneumoniae. Today, 44% of all S. pneumoniae isolates in the United States have reduced susceptibility to penicillin. In some areas of the country, many penicillin-resistant strains are also multidrug resistant. Consequently, ceftriaxone plus a fluoroquinolone is the treatment of choice for cases of penicillin-resistant S. pneumoniae. When these drugs fail (or as an alternate first-line therapy), vancomycin plus azithromycin may be used.

Although a vancomycin-resistant strain of S. pneumoniae hasn't been reported, the three most common bacterial causes of AOM (Moraxella catarrhalis, Haemophilus influenzae, and S. pneumoniae) have shown increasing antimicrobial resistance. For example, M. catarrhalis and H. influenzae produce beta-lactamases that render penicillin ineffective. Because of S. pneumoniae's increased resistance to penicillin, the CDC recommends using amoxicillin to treat a patient with AOM. If he doesn't improve after 3 days of starting amoxicillin, he should receive high-dose amoxicillin/ clavulanate (Augmentin), clindamycin, cefuroxime axetil, or one to three doses of intramuscular ceftriaxone. Use standard precautions when caring for patients with penicillin-resistant S. pneumoniae.

ESBLs: Removing the ring

First reported in 1983, ESBLs are enzymes produced by Klebsiella pneumoniae, Eschenchia coli, and other Gram-negative bacteria. These enzymes destroy the beta-lactam ring in certain antibiotics, rendering them ineffective.

Researchers have identified 255 ESBLs capable of destroying the beta-lactam ring in antibiotics such as third- and fourth-generation cephalosporins, extended-spectrum penicillins, and aztreonam. Aminoglycosides, chloramphenicol, sulfonamides, and trimethoprim/ sulfamethoxazole are also ineffective against ESBLs. However, ESBLs usually respond to a fluoroquinolone.

Although costly, carbapenem is the treatment of choice for patients infected with an ESBL-producing bacterium. Decreasing the use of third-generation antibiotics and replacing them with other broad-spectrum antibiotics can decrease the incidence of ESBL in hospitals. Use standard precautions when caring for patients with an ESBL-producing organism.

Beyond antibiotics

How do we finally defeat the constant stream of multidrug-resistant microorganisms? Creating new antibiotics isn't the answer; new strains of resistant microbes will always emerge. Instead, we must change the way we think about these microbes.

Toward this goal, the CDC has begun the Campaign to Prevent Antimicrobial Resistance in Healthcare Settings. The campaign promotes four strategies to overcome antimicrobial resistance: preventing infection, diagnosing and treating infection, using antimicrobials wisely, and preventing transmission. Learn more about these strategies at the CDC Web site included in Selected Web Sites.

Here are some other promising approaches on the horizon:

* Probiotics. According to the probiotics theory, harmless microbes can be used to overwhelm a disease-causing microorganism. For example, researchers have successfully used Lactobacillus, commonly found in yogurt cultures, to treat diarrhea caused by C. difficile.

* Synthetic drugs. The new antimicrobial drug linezolid is the first member of a class of completely synthetic drugs called oxazolidinones. Because linezolid is synthetic, bacteria haven't been exposed to it. Researchers doubt that preexisting resistance exists; however, resistance will likely emerge.

* Resistance mechanisms. Researchers are working on developing a drug that targets a microbe's resistance mechanism. Taken at the same time as an antibiotic, a resistance drug would make the antibiotic effective again.

* New penicillins. Ureidopenicillins and new beta-lactam/beta-lactamase inhibitor combinations are the latest additions to the penicillin family. The success of amoxicillin/ clavulanate will lead to the development of second-generation betalactamase inhibitors that can combat newer beta-lactamases.

* Molecular advances. Progressive research in molecular biology continues, and researchers have decoded many microbes' genomes. With this information, they can develop drugs that target a microbe's vital functions or virulence factors (for example, toxins).

* Vaccine development. The vaccine against pneumococci is effective and inexpensive. Researchers are developing new vaccines against other resistant bacteria.

* Natural compounds. Asian cultures have used the roots of Arbenia euchroma (rubricine) for centuries to help heal wounds and burns. Researchers are studying rubricines ability to stop and destroy bacteria, including those that are multidrug-resistant.

Changing our habits

Today the line between nosocomial infection and community-acquired infection has blurred. Patients move quickly from setting to setting, and health care workers rotate from one location to another. The average hospitalized patient is older and more acutely ill than his predecessors. Patients who have decreased immunity and have had multiple hospitalizations and multiple courses of antibiotics are especially vulnerable to infections from multidrug-resistant microorganisms.

All prescribers must assume responsibility for the problem of antibiotic resistance, and all direct caregivers must take responsibility for preventing microorganism transmission. Prescribers must know the prevalence and susceptibility patterns of bacteria in their practice areas and in each patient population. And they must know when and what to prescribe, use the narrowest spectrum antibiotic that's effective against a given microorganism, and avoid indiscriminate use of broad-spectrum antibiotics.

Infection control practitioners should be consulted if the health care provider can't determine the causative microorganism. These practitioners can help determine when to initiate treatment and with what antibiotic.

As nurses, we play a key role in educating patients on the appropriate use of antibiotics (see Helping Your Patient Do His Part). We must also adhere to current infection control standards and be well informed about new microbial threats and treatment advances.

Most important, we must remember that good hand hygiene is still the easiest, cheapest, and best way to protect everyone's health.

SELECTED REFERENCES

Chang, S., et al.: "Infection with Vancomycin-Resistant Staphylococcus Aureus Containing the vanA Resistance Gene," The New England Journal of Medicine. 348(14):1327-1342, April 2003.

Hellinger, W.: "Confronting the Problem of Increasing Antibiotic Resistance," Southern Medical Journal. 93(9):842-848, September 2000.

Noskin, G., et al.: "Persistent Contamination of Fabric-Covered Furniture by Vancomycin-Resistant Enterococci: Implications for Upholstery Selection in Hospitals," American Journal of Infection Control. 28(4):311-313, August 2000.

Pagani, L., et al.: "Emerging Extended-Spectrum Beta-Lactamases in Proteus Mirabilis," Journal of Clinical Microbiology. 40(4):1549-1552, April 2002.

Paterson, D.: "Extended-Spectrum Beta-Lactamases: The European Experience," Current Opinion in Infectious Disease. 14(6):697-701, December 2001.

Year 2003 ASCAP Panel: "Community-Acquired Pneumonia (CAP): Evidence-Based Antibiotic Selection and Outcome-Effective Patient Management-Year 2003 Update," Hospital Medicine Consensus Reports. 1-40, March 30, 2003.

Ziglam, H., et al.: "Penicillin-Resistant Pneumococci-Implications for Management of Community-Acquired Pneumonia and Meningitis," International Journal of Infectious Diseases. 6(Suppl. 1):S14-S20, March 2002.

BY BARBARA SHEFF, RN, CPH, HNC, MT(ASCP), MA

Barbara Sheff is a microbiology consultant in Boston, Mass.

Copyright Springhouse Corporation Nov 2003
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