Strategies for preventing and reducing contamination by drug-resistant pathogens help to decrease the occurrence of VAP and improve patient outcomes.

zoidis.jpg (10363 bytes)Nosocomial pneumonia that occurs in association with mechanical ventilation has become a clinical entity so well recognized that a relatively new term used to describe it—ventilator-associated pneumonia (VAP)—has gained widespread acceptance. Risk factors for VAP may be categorized as host-related factors, infection-control practices, endotracheal-tube factors, gastrointestinal factors, and the effects of body position.

Host-related risk factors for VAP include an age of more than 65 years, underlying illness (particularly chronic obstructive lung disease), immunosuppression, coma, prolonged hospitalization, and thoracic or abdominal surgery.

Infection Control Practices
Hand washing is an important component in reducing the incidence of VAP. The administration of antibiotics in the intensive care unit (ICU) is also an important factor in the development of VAP. Prior antibiotic therapy can lead to the emergence of antibiotic-resistant strains of bacteria. Patients who have been previously treated with antibiotics are more likely than those who have not to be infected with high-risk pathogens such as Pseudomonas aeruginosa. In addition, the incidence of sepsis, septic shock, and death may be increased in patients infected with resistant strains of bacteria.

Direct effects of an endotracheal tube include mucosal injury, impaired mucociliary function, and a reduction in upper-airway defenses due to an ineffective cough mechanism. The presence of an endotracheal tube may contribute indirectly to the risk of VAP by creating binding sites for bacteria in the bronchial tree and by increasing mucus secretion. Stagnation of secretions promotes the growth and proliferation of bacterial pathogens. In addition, the endotracheal tube may serve as a reservoir for bacteria that are inaccessible to host defense systems.

Bacterial colonization of the oropharynx may also contribute to the risk of VAP. Endotracheal intubation allows leakage around the tube of oropharyngeal secretions laden with bacteria. For this reason, continuous aspiration of subglottic secretions may reduce the incidence of VAP.

The risk of VAP caused by contaminated respiratory equipment is low. The internal machinery of mechanical ventilators is not considered an important source of bacterial contamination. Most ventilators have either bubble-through or wick humidifiers that produce little or no aerosol for humidification; therefore, the risk of causing pneumonia is low. Bacteria from the patient’s oropharynx can, however, contaminate the inspiratory circuit, and spillage of contaminated condensate into the patient’s tracheobronchial tree may increase the risk of VAP.

Several gastrointestinal factors are believed to increase the risk of VAP. These include the presence of a nasogastric tube, gastric alkalinization, and the use of enteral feedings. Gastric alkalinization with antacids and/or histamine-2 receptor antagonists is sometimes done to prevent stress-induced gastritis, but it has been implicated as a risk factor for VAP. These agents increase the pH of the gastric secretions; this, in turn, affects the normal flora of the entire gastrointestinal tract. Pathogens that proliferate in gastric secretions may increase the likelihood of VAP. The alkalinized stomach is a particularly attractive breeding ground for gram-negative enteric bacteria. A gastric pH greater than 3.5 may predispose one to bacterial colonization of the lower respiratory tract.

Preventive Strategies
Based on an understanding of the pathogenic mechanisms and risk factors for VAP, several preventive strategies can be recommended. These strategies can be divided into three groups: methods to reduce bacterial colonization, techniques to reduce aspiration of oropharyngeal secretions, and strategies to reduce aspiration of gastric secretions. The maintenance of adequate nutrition (see sidebar) is also an important consideration in all critically ill or injured patients, including those who are intubated.
Perhaps the most effective means of preventing VAP caused by exogenous microorganisms is consistent, thorough hand washing. All health care personnel should wash their hands before and after contact with patients. Hands should also be washed before and after contact with patient respiratory equipment or respiratory secretions. Hand washing should be performed whether or not gloves are worn.
In addition to hand washing, universal precautions should be observed. Gloves should be worn if contact with respiratory secretions or contaminated objects is anticipated. Gowns are useful if it is expected that the health care worker’s clothes may be soiled. The cornerstone of the successful implementation of universal precautions is regular changing of gloves and gowns. Gloves and gowns should be changed and hands should be washed after any contaminating event and before touching any other patient, object, or environmental surface.
Maintenance of oral and nasal hygiene is another useful means of reducing bacterial colonization. Instead of just swabbing the patient’s mouth, teeth should be brushed and a mouthwash solution should be applied to the oral cavity. In addition, oral secretions should be adequately removed through suction. Regular oral assessment should be a part of the routine care of all intubated patients. In addition to oral hygiene, meticulous nasal care and cleansing of the nasopharynx may reduce bacterial colonization. Nasal hygiene is a frequently neglected component of the overall care of the intubated patient. If a nasoenteric or nasotracheal tube has been in place for a prolonged period, secretions may accumulate in the nares. Nasopharyngeal secretions should be removed via suction regularly.
Since stagnating lower-pulmonary secretions create a nourishing environment for bacterial pathogens, routine turning and positioning of the patient are often recommended to promote mobilization of secretions and reduce the likelihood of colonization. The use of beds that provide continuous lateral rotation therapy is currently being evaluated in clinical trials to determine whether they are associated with a true reduction in the incidence of VAP. Even in the absence of conclusive data, however, frequent postural changes make good clinical sense.
An issue that is constantly undergoing reevaluation is how frequently endotracheal suction should be performed. Many institutional ICU protocols call for suction to be performed only when there is an apparent need to do so. The rationale for this approach is that infrequent suction reduces trauma to the airways. Applying this rationale, however, means that patients who have only minimal secretions may remain without suction for many hours. Because stagnating mucus and the lack of an adequate cough reflex are risk factors for the development of VAP, suction may be needed periodically. Although no uniform guidelines exist regarding this issue, it is probably a good idea to perform suction on all intubated patients on at least a semiregular basis.
If prophylaxis against stress ulcers is warranted, as for patients who remain intubated for long periods of time, then the use of agents (such as sucralfate) that do not alter the gastric pH is preferred. Unfortunately, it is not always feasible to use sucralfate because it must pass through the stomach to be therapeutically effective, and many critically ill patients have intestinal tubes. In such cases, protocols should be developed that stipulate precise clinical indications for stress-ulcer prophylaxis.
A new approach to the reduction of bacterial colonization (and, hence, VAP risk) is selective digestive decontamination. This procedure has been evaluated in mechanically ventilated patients in Europe. In selective digestive decontamination, a nonabsorbable antibiotic paste is applied locally to the oropharynx and is administered via nasogastric tube three to four times per day. Unfortunately, the results of clinical trials investigating the usefulness of selective digestive decontamination in reducing the risk of VAP have been mixed.

ReducING Aspiration
Because aspiration of oropharyngeal secretions is a primary mechanism for the development of VAP, strategies that reduce aspiration of secretions may significantly reduce the risk of VAP. Perhaps the simplest method of reducing VAP risk is to extubate patients as soon as possible. The longer an endotracheal tube remains in place, the greater the amount of stagnant lower pulmonary secretions and the greater the chance for bacterial colonization. In addition, it is important to take precautions to prevent accidental extubation, because reintubation increases the risk of VAP. Endotracheal cuff pressures should be checked periodically to make sure that a pressure of at least 20 cm H2O is maintained. The incidence of VAP increases when endotracheal cuff pressures fall below 20 cm H2O. Finally, it is important to perform thorough oral suction whenever endotracheal tubes are repositioned in order to reduce the pooling of secretions above the tube.
An innovative type of endotracheal tube, long available in Europe but only recently introduced in the United States, may also diminish the risk of VAP. It is an endotracheal tube with a suction lumen that allows for continuous or intermittent suction of subglottic secretions that pool above the cuff. Contaminated secretions that pool above the cuff are a potential source of VAP; therefore, removal of these secretions may decrease the risk of airway contamination and, hence, may prevent or delay the onset of VAP.
Several strategies can be used to reduce the potential for introduction of gastrointestinal contents and microorganisms into the respiratory tract. Elevating the head of the patient’s bed 30° to 45°, particularly if he or she is being fed enterally, helps prevent gastric reflux and reduces the risk of aspiration. Nasogastric tubes, if used, should be removed as soon as possible. If long-term enteral feedings are required, then the patient should be evaluated for placement of a gastrostomy or jejunostomy feeding tube. If nasogastric tubes must be used, then the verification of postpyloric placement is essential. Whatever feeding method is used, bowel sounds should be assessed regularly to ensure that the rate and volume of enteral feedings are appropriate for the patient’s gastrointestinal function; feeding too much or too rapidly can increase the risk of regurgitation and aspiration.

Drug-Resistant Pathogens
Resistance of microorganisms to antimicrobial medications has existed since the first antibiotics were introduced. Over the years, clinicians have tried to stay one step ahead of the evolution of resistant microorganisms. Today, antimicrobial resistance is a growing problem, both in hospitals and in the community. The rapid emergence of resistance to antimicrobial drugs among infectious pathogens is quickly diminishing the treatment options for several common infections, particularly those acquired in the hospital. In particular, antimicrobial resistance among common respiratory pathogens has become a significant problem.

Resistance of microorganisms to antimicrobial therapy has probably emerged in response to various conditions. These include the availability of new surgical procedures, often involving long operative duration; use of more (and new) types of instrumentation and devices; presence of a greater number of patients with decreased immunocompetence, serious acute disease, or chronic illness; the AIDS epidemic; fewer resources for education and infection control; inability of some laboratories or laboratory procedures to detect microbial resistance; breakdowns in aseptic technique; community factors such as clustering and overcrowding; inadequate sanitation in shelters and living areas; population mobility; widespread use of broad-spectrum antibiotics as prophylaxis, in therapy, and in the community; over-the-counter sale and self-dosing with antibiotics; poorly regulated drug manufacture in some places; decreased funding for public-health surveillance; fewer disease-control programs; inappropriate therapeutic prescriptions; and nonadherence to prescribed therapy.1

Antibiotic Resistance in Respiratory Pathogens
Respiratory tract infections (RTIs) are a serious problem worldwide. These infections are very prevalent and continue to be a leading cause of death.2 Although numerous microorganisms can produce RTIs, the most common bacterial pathogens are Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis, as well as Mycobacterium tuberculosis. During recent years, the prevalence of drug resistance in respiratory pathogens has increased dramatically worldwide.2

Several risk factors for penicillin-resistant and multiple-drug–resistant pneumococci have been reported. One study3 found that previous use of b-lactam antibiotics, noninvasive disease, alcoholism, and an age of less than 5 or more than 64 years were independently associated with drug-resistant pneumococci. Other studies4,5 also found an association between previous antibiotic use and the isolation of penicillin-resistant pneumococci.

Currently, in many parts of the world, antibiotic resistance to H. influenzae and M. catarrhalis is of increasing concern. The main mechanism of resistance is b-lactamase production, which makes these strains resistant to penicillin, ampicillin, and amoxicillin. The emergence of other antibiotic resistance has, with some exceptions, been relatively low. An ongoing, international multicenter study6 that included 1,843 strains of H. influenzae showed that the incidence of b-lactamase production was 28.4% in the United States and 15.4% in Europe.

In the late 1980s, resistance of M. tuberculosis to antimycobacterial agents emerged as a serious challenge to tuberculosis control worldwide. Multidrug-resistant tuberculosis is commonly conceived as having resistance to two or more first-line anti-tuberculosis drugs or resistance to, at least, isoniazid and rifampin.7 Both primary and acquired drug resistance may occur. The latter could be induced by inappropriate prescription, poor patient compliance, or an insufficient number of active drugs in the therapeutic regimen.

Emerging Strains
Gram-positive infections have become an increasing problem in recent years, particularly in the nosocomial setting. Data from the National Nosocomial Infection Surveillance (NNIS) program indicate that enterococci and staphylococci account for more than 50% of isolates from infected blood, and an additional 4% are streptococci.8 A more recent investigation conducted at 43 medical centers throughout the United States documented that a total of 60% of isolates from blood infections were gram-positive species.9

Vancomycin-Resistant Enterococci
Vancomycin-resistant enterococcus (VRE), a highly resistant strain of enterococcus, was first reported in Europe in 1988 and is becoming an increasing concern worldwide. VRE is sometimes called VREF, which can stand for vancomycin-resistant Enterococcus faecalis or vancomycin-resistant E. faecium. Vancomycin is an extremely potent intravenous antibiotic. When bacteria become resistant to vancomycin, it means that the infection has become difficult to treat. VRE strains are likely to be resistant to antibiotics other than vancomycin, particularly penicillins.

VRE is a recognized cause of intra-abdominal infections, as well as endocarditis, urinary tract infections, wound infections, and bacterial sepsis. Vancomycin use in US hospitals has increased dramatically in the past 10 to 15 years due to a variety of factors, including increases in the incidence of methicillin-resistant Staphylococcus aureus (MRSA), prosthetic-device–related infections, Clostridium difficile colitis, and inappropriate use of the drug. The use of vancomycin and other antimicrobial drugs is an important risk factor for human VRE infection.

MRSA infection
MRSA was first described in 1961, shortly after the introduction of penicillinase-resistant b-lactam antibiotics into clinical practice. Since then, hospitals worldwide have reported varying proportions of MRSA among S. aureus isolates. Over time, several MRSA isolates have acquired resistance to other antibiotics; thus, MRSA has become a real clinical and therapeutic problem.

Today, MRSA is a major nosocomial pathogen found in an increasing number of hospitals worldwide. According to data from the NNIS, the percentage of MRSA among all S. aureus isolates rose from 2% in 1975 to 29% in 1991.10,11 This is a frightening fact that affects not only large teaching hospitals, but also small hospitals and nursing homes.12

S. aureus is one of the most common causes of both hospital- and community-acquired infections worldwide, and the antimicrobial agent vancomycin has been used to treat many S. aureus infections, particularly those caused by MRSA. Although S. aureus remains susceptible to vancomycin, the emergence of strains with only intermediate susceptibility to the antibiotic is raising fears that the emergence of a fully resistant strain is not too far off.

Organisms are deemed susceptible to vancomycin if the minimum inhibitory concentration is less than or equal to 4 µg/mL, intermediately susceptible at 8 to 16 µg/mL, and resistant at 32 or more µg/mL.

The first report of infection with a strain of S. aureus that had only intermediate susceptibility to vancomycin came from Japan in June 1996.13 This report raised concern among infectious disease experts and led the Centers for Disease Control and Prevention (CDC) to issue interim recommendations about how to control such vancomycin-intermediate S. aureus (VISA) infections.14 More recently, two reports of VISA infection in the United States were published.15,16

The mechanism through which staphylococci become resistant to vancomycin is not clearly understood. Investigators have isolated a vancomycin-resistant S. aureus mutant in vitro that appeared to have structural cell-wall alterations that increase its ability to bind vancomycin.10 The researchers have theorized that this alteration may prevent vancomycin from reaching crucial sites of cell-wall synthesis, thus impeding its bactericidal effect.

Most cases of VISA infection have one feature in common: the organism was initially sensitive to the antibiotic, but a moderately resistant strain was subsequently isolated after prolonged vancomycin use.

The CDC recommends that all clinical isolates of S. aureus be tested for susceptibility to vancomycin. Laboratory personnel should notify the laboratory director if vancomycin-resistant or vancomycin-sensitive S. aureus is discovered. Many isolates of S. aureus presumed to have been vancomycin-resistant have been found to be mixed with other organisms in cultures; therefore, vancomycin resistance should be confirmed by restreaking the colony to certify that the culture is pure. The hospital epidemiology program should be notified so that it can institute appropriate isolation procedures. The public health department, other hospitals in the vicinity, and the CDC should also be notified.

CDC Guidelines
The guidelines issued by the CDC14 in response to the clinical isolation of drug-resistant pathogens are more stringent than those previously published. If a drug-resistant pathogen is isolated, the physician and staff should:
• notify the state health department and the CDC’s hospital infections program;
• inform all personnel involved in the care of the patient and educate them on infection-control precautions;
• isolate the patient in a private room and institute appropriate contact precautions for all staff, including gowning, gloving, and hand washing with antibacterial soap;
• assign specific workers to provide one-on-one care for the patient;
• minimize the number of persons with access to the patient;
• avoid transferring the patient, if this is possible;
• monitor compliance with contact precautions closely;
• initiate an epidemiologic and microbiologic investigation;
• obtain baseline cultures from the patient and the hands of roommates and all persons in direct contact with the patient; and
• obtain additional information. State health departments and the CDC can provide information about surveillance cultures and the management of the patient’s discharge. The US Food and Drug Administration can provide information on investigational antimicrobial agents.

By implementing a variety of strategies proven to reduce the risk of VAP, health care personnel may be able to decrease the occurrence of VAP and improve patient outcomes. These simple and effective strategies are designed to reduce bacterial colonization and prevent aspiration of oropharyngeal and gastric secretions. The application of newer preventive techniques may play an important role in reducing the risk of VAP.

John D. Zoidis, MD, is a contributing writer for RT Magazine.

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