It is important for health care workers in the ICU to understand how infections occur and the prevalent microorganisms that cause disease
Many infections are seen in the ICU. Among the more serious are nosocomial pneumonia, community-acquired pneumonia (CAP), complicated intra-abdominal infection, endocarditis, and skin and skin structure infections. In cancer patients who are receiving chemotherapy, neutropenia combined with fever is a dangerous combination because it may signal the presence of an infection. Because of the immunosuppressive effect of chemotherapy, such a patient may be unable to mount an adequate defense against that infection.
Most patients who have nosocomial pneumonia are infants, young children, and persons >65 years of age. Patients who have severe underlying disease, immunosuppression, depressed sensorium, and/or cardiopulmonary disease are also susceptible to nosocomial pneumonia. In addition, thoracoabdominal surgery is a major risk factor for nosocomial pneumonia. Although patients receiving mechanically assisted ventilation do not represent a major proportion of patients who have nosocomial pneumonia, they are at highest risk for acquiring the infection.
According to surveillance data from the National Nosocomial Infection Surveillance (NNIS) program, pneumonia is the second most common nosocomial infection overall1 and the most common nosocomial infection in intensive care units,2 accounting for 15% of all nosocomial infections and 31% of those in ICUs. Infection rates for nosocomial pneumonia in mechanically ventilated patients are very high, ranging from eight to 54 cases per 100 patients, with a median of 27 cases per 100 patients.3
Of the different types of nosocomial infection, pneumonia is responsible for the greatest mortality. In a study of 200 hospital deaths,4 pneumonia was implicated in 60% of deaths for which nosocomial infection was a contributing factor. In a matched cohort study,5 the attributable mortality of nosocomial pneumonia was estimated to be 33%; in other words, roughly one-third of patients who developed nosocomial pneumonia and died would not have died otherwise.
Substantial morbidity is also associated with nosocomial pneumonia. Secondary bacteremia and empyema are common sequelae. Estimates of the excess duration of hospitalization resulting from nosocomial pneumonia range from 4 to 9 days, with a median of 7.7 days.3 The excess cost of health care related to nosocomial pneumonia may be as high as $1 billion annually.6
Most bacterial nosocomial pneumonias occur by aspiration of bacteria colonizing the oropharynx or upper gastrointestinal tract of the patient. Because intubation and mechanical ventilation alter first-line patient defenses, they greatly increase the risk for nosocomial bacterial pneumonia. Pneumonias caused by Legionella species, Aspergillus species, and influenza virus are often caused by inhalation of contaminated aerosols. Respiratory syncytial virus (RSV) infection usually occurs after viral inoculation of the conjunctivae or nasal mucosa by contaminated hands.
Bacterial nosocomial pneumonias are frequently polymicrobial, and gram-negative bacilli are usually the predominant organisms. However, Staphylococcus aureus (particularly methicillin-resistant S. aureus [MRSA]) and other gram-positive cocci such as Streptococcus pneumoniae have emerged recently as important isolates. In addition, Haemophilus influenzae has been isolated from mechanically ventilated patients who had pneumonia that occurred within 48-96 hours after intubation.5,6
Over the last decade, the development of MRSA has been a growing problem in the nosocomial setting. These organisms are capable of causing widespread outbreaks of serious infection and colonization, especially among surgical and critically ill patients. The epidemiology of ventilator-associated pneumonia by MRSA appears to be quite different from that of methicillin-sensitive S. aureus (MSSA). In a recent study, Rello et al7 reported that patients with ventilator-associated pneumonia due to MRSA were significantly more likely to have received prior steroids, mechanical ventilation for more than 6 days, or prior antibiotic therapy. In addition, patients with ventilator-associated pneumonia due to MRSA were more likely to be older than 25 years and to have had previous chronic lung disease than those with ventilator-associated pneumonia due to MSSA.
In hospitals participating in the NNIS, Pseudomonas aeruginosa, Enterobacter species, Klebsiella pneumoniae, Escherichia coli, Serratia marcescens, and Proteus species comprised 50% of isolates from cultures of respiratory tract specimens obtained from patients with nosocomial pneumonia; S. aureus accounted for 16%, and H. influenzae, for 6%.8 One study reported that gram-negative bacilli were present in 75% of patients who had acquired nosocomial pneumonia after receiving mechanically assisted ventilation; 40% of these cultures were polymicrobial.9
CAP is an acute lower respiratory tract infection that develops in nonhospitalized individuals. It remains a common and serious illness despite the availability of potent antibiotics. Patients with severe CAP may require admission to the ICU.
In recent years, both the causes and the treatment of CAP have undergone changes. CAP is increasingly common among older people and those with coexisting illness. Such illnesses include chronic obstructive lung disease, diabetes, kidney failure, and congestive heart failure. These patients may become infected with a variety of newly identified or previously unrecognized pathogens. At the same time, bacterial resistance to antibiotics has been on the rise, making treatment difficult.
The most common pathogens are S. pneumoniae, H. influenzae, Mycoplasma pneumoniae, and Moraxella catarrhalis. S. pneumoniae is the most common cause of CAP, accounting for up to 75% of cases.10 The identification of more than one pathogen in an individual with CAP is unusual, occurring in <10% of cases.11 Newly recognized etiologic agents include Chlamydia pneumoniae, Legionella species, and Hanta virus.12
Complicated Intra-Abdominal Infection
Intra-abdominal infections are caused as a rule by bacteria that are part of the normal flora of the gastrointestinal tract. In most cases, the normal flora has escaped from inside the bowel by means of a breach of normal anatomic barriersa rupture or inflammation of an organor because of surgery. Usually these infections are polymicrobial and contain both aerobic and anaerobic bacteria. In many cases, intra-abdominal infection can lead to abscess formation. Examples of intra-abdominal infections include peritonitis, intra-abdominal abscess, appendicitis, diverticulitis, cholecystitis, and cholangitis.
Generally, the antibiotic therapy of intra-abdominal infections is directed against both aerobic and anaerobic bacteria. If antibiotic coverage is not aimed at both aerobic and anaerobic organisms, then clinical failure is common. Empiric antibiotic therapy is usually begun before a definitive diagnosis of causative organisms has been made.
The term endocarditis refers to inflammation of the endocardium. The endocardium is the innermost layer of the heart, and includes the heart valves. Endocarditis remains a serious medical problem despite advancements in laboratory detection and the availability of newer antibiotic agents. In recent years, a greater frequency of endocarditis has been seen in the elderly, in intravenous drug users, and in patients with prosthetic valves.
An enormous number of bacterial and other pathogens can cause endocarditis. Streptococci are the most common cause, and S. aureus is the second-most common cause.13 Enterococci and Corynebacterium species are also frequently implicated as causative pathogens.13 Others include P. aeruginosa, Sternotrophomonas (Xanthomonas) maltophilia, Acinetobacter species, Yersinia enterocolitica, Campylobacter species, Neisseria gonorrhoeae, Brucella species, Legionella species, Veillonella species, Clostridium species, and HACEK organisms (Haemophilus species, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae).13
The ability of bacteria to stick to the endocardial surface probably plays an important role in the pathogenesis of endocarditis. A variety of microorganisms can cause endocarditis, including staphylococci and enterococci.
Important changes have taken place in the management of endocarditis. There is a clear trend toward the use of shorter treatment courses, oral and once-daily regimens, and outpatient programs, all of which aim to reduce costs and provide patients with improved quality of life. Antibiotic prophylaxis for the prevention of endocarditis is still controversial. In the past few years, more regimens have been used, and indications are now more precise. In spite of all this, however, few cases seem to be prevented and patient compliance to the prophylaxis regimens remains low.
The choice of antibiotic is essential in the management of endocarditis. The infecting pathogen(s) should be isolated before the initiation of antibiotic therapy if possible. The antibiotics selected should be effective against known pathogens, and treatment should continue long enough to sterilize the heart valves and endocardium of bacterial vegetations.
Skin and Skin Structure Infection
Primary skin infections are very common and arise in otherwise healthy individuals. Initially, primary skin infections are usually due to a single organism, most commonly S. aureus. Another pathogen commonly seen in primary skin infections is Streptococcus species. Patients with primary skin infections may develop a rash with itching. The itching and mild pain are usually followed by progressive local swelling and erythema.
Secondary skin infections develop in damaged or diseased skin following an insult to host defenses and the integrity of the skin. The insult is usually in the form of trauma, such as a cut, burn, scrape, or other type of wound. Secondary skin infections are less common then primary skin infections. Unlike primary infections, they do not follow a characteristic course. The pathogens implicated in secondary skin infections include gram-negative organisms as well as Staphylococcus species and Streptococcus species.
Examples of primary skin infections include impetigo, folliculitis, ecthyma, cellulitis, erysipelas, furuncles, carbuncles, and necrotizing fasciitis. Severe cases warrant admission to the ICU and intravenous antibiotic therapy.
Necrotizing fasciitis is a serious, progressive inflammation of the fascia, a sheet of fibrous tissue that envelops the body beneath the skin and divides muscles into compartments. Several severe cases of necrotizing fasciitis over the last few years have received widespread press coverage. The press has frequently referred to necrotizing fasciitis as the flesh-eating disease or skin-eating bacteria. The most common sites of involvement are the extremities, trunk, genital area, head, and neck. Streptococcus species is the most common pathogen that causes necrotizing fasciitis. Other organisms include Enterobacter species, Bacteroides species, Peptostreptococcus species, and Clostridium species. In many cases, necrotizing fasciitis is a polymicrobial infection. Fluid drained from polymicrobial necrotizing fasciitis infections has been called dishwater pus. Treatment of necrotizing fasciitis involves surgical debridement of all necrotic tissue in combination with high-dose, appropriate antibiotics. It is imperative to begin broad-spectrum antibiotic coverage until the causative pathogen(s) is (are) identified.
Fever in Neutropenic Patients
Neutropenia combined with fever is a dangerous combination because it signals the presence of an infection in a patient who may be unable to mount an adequate defense against that infection. Because fever may be the only sign of infection in neutropenic patients, its appearance commands a series of diagnostic measures and empiric antibiotic therapy.
Until recently, all febrile neutropenic patients were hospitalized for the administration of empiric, broad-spectrum, intravenous antibiotic therapy. This approach was considered necessary because a substantial number of febrile episodes, particularly in patients with prolonged and profound neutropenia, were caused by bacterial and fungal pathogens and were associated with an unacceptable risk of complications, including septic shock and death, unless treated promptly and aggressively.
In recent years, the concept of risk assessment during the initial phases of a febrile episode has been introduced and evaluated. It is now possible to identify subsets among febrile neutropenic patients with varying degrees of risk related to risk factors such as the presence of concurrent diseases, the disease status of the underlying malignancy, and other clinical characteristics.
The most common causes of infection in febrile neutropenic patients are gram-negative bacilli and gram-positive cocci.14 Fungal infections tend to occur in cases of prolonged and severe neutropenia. Viral infections (such as those with herpes simplex or varicella zoster virus) are seen mainly in patients with acute leukemia or lymphomas, and in those who have undergone bone marrow transplantation.
The incidence of infections caused by P. aeruginosa in febrile neutropenic patients has decreased substantially in recent years.14 Similarly, the incidence of infection by gram-positive organisms such as S. aureus has increased.14
General management principles for febrile neutropenic patients are as follows:
evaluate the patient at least daily;
initiate prompt therapy with broad-spectrum antibiotics when a patient with neutropenia (neutrophil count <500 cells/mm3) becomes febrile;
if the patient has an indwelling intravenous catheter, obtain cultures from the catheter as well as from a peripheral vein;
monitor the patient closely for secondary infections requiring additions or modifications to the initial antibiotic regimen;
continue empiric antibiotic therapy if the patient has prolonged (more than 1 week) neutropenia, particularly if there is persistent fever;
add empiric antifungal therapy if a patient with neutropenia remains febrile after a week of broad-spectrum antibiotic therapy or has recurrent fever;
although 10 to 14 days of treatment is adequate in most patients with neutropenia, prolonged therapy is necessary for patients with a residual focus of infection or an invasive fungal infection; and
all health care personnel caring for a febrile neutropenic patient should wash their hands carefully before and after contact with the patient.
Infection Control in the ICU
A number of relatively simple control measures can reduce the risk of developing nosocomial infection, particularly in ventilator-dependent patients. These measures may also improve the chance for successful outcome in patients with either existing infection or nosocomial infection.
Cross colonization plays a major role in the spread of nosocomial infections. Gram-negative bacilli are ubiquitous and are often present in high concentrations in critically ill patients. Proper handwashing before and after patient contact is an effective means of removing transient bacteria. The use of gloves and gowns may significantly reduce the incidence of nosocomial infections among patients in the ICU.
Continuous Aspiration of Subglottic Secretions
Devices that circumvent host defenses or facilitate the entry of bacteria into the lung are of great concern. The presence of an endotracheal tube impairs natural host defenses against infection and increases the risk of ventilator-associated pneumonia. Leakage around the cuff allows subglottic secretions pooled above the cuff to enter the trachea. Mahul and associates15 reported a decrease in the incidence of ventilator-associated pneumonia using manual intermittent aspiration of subglottic secretions. In a more recent study, Valles and coworkers16 reported that the use of continuous aspiration of subglottic secretions (CASS) significantly reduced the incidence of ventilator-associated pneumonia. The effect was most dramatic during the first 2 weeks of intubation and was primarily associated with a reduction of H. influenzae and gram-positive cocci.
The potential for pneumonia in patients using mechanical ventilators that have heated bubble-through humidifiers stems primarily from the condensate that forms in the inspiratory-phase tubing of the ventilator circuit as a result of the difference in the temperatures of the inspiratory-phase gas and ambient air. Condensate formation increases if the tubing is unheated. The tubing and condensate can rapidly become contaminated, usually with bacteria that originate in the patients oropharynx.
In 1983, the Centers for Disease Control and Prevention (CDC) recommended changing ventilator breathing circuits at 24-hour intervals. That recommendation has recently been altered to state that ventilator circuits should not be changed more frequently than every 48 hours, with no recommendation for the maximum time between circuit changes.8 It has become increasingly recognized that the ventilator circuit may be a source of nosocomial pneumonia. Humidification is almost always accomplished using heated nonaerosol generating devices, and it has been shown that the temperature of these humidifiers often inhibits bacterial growth.17 Contamination of the ventilator appears to be similar at 24 and 48 hours after a circuit change. Moreover, contamination of the circuit is often from the patient, rather than an exogenous source. Contamination of the lower respiratory tract in mechanically ventilated patients is often the result of aspiration of oropharyngeal secretions rather than aerosolization from the ventilator circuit.
Use of a Heat-Moisture Exchanger
According to the recent CDC guidelines for the prevention of nosocomial pneumonia,8 condensate formation can also be eliminated by using a heat-moisture exchanger (HME) or a hygroscopic condenser humidifier (eg, an artificial nose). An HME recycles heat and moisture exhaled by the patient and eliminates the need for a humidifier. In the absence of a humidifier, no condensate forms in the inspiratory-phase tubing of the ventilator circuit. Thus, bacterial colonization of the tubing is prevented, and the need to change the tubing on a periodic basis is obviated. Some models of HMEs are equipped with bacterial filters, but the advantage of using such filters is unknown. Further study is needed to definitively determine whether the use of HMEs can decrease the incidence of nosocomial pneumonia.
Avoidance of Handheld Nebulizers
Small-volume medication nebulizers used to administer bronchodilators, including nebulizers that are handheld, can produce bacterial aerosols. Handheld nebulizers have been associated with nosocomial pneumonia, including legionnaires disease, resulting from either contamination with medications from multidose vials or Legionella-contaminated tap water used for rinsing and filling the reservoir.
Proper Cleaning and Sterilization
Proper cleaning and sterilization or disinfection of reusable equipment are important components of a program to reduce infection associated with respiratory therapy. If a respiratory device needs rinsing to remove a residual liquid chemical sterilant or disinfectant after chemical disinfection, sterile water is preferred because tap or locally prepared distilled water might contain microorganisms that can cause pneumonia. In some hospitals, a tap-water rinse followed by air-drying with or without an alcohol rinse is used. In theory, if complete drying is achieved after a tap-water rinse, the risk for nosocomial pneumonia associated with the use of the device is probably low. Air drying reduces the level of microbial contamination of health care personnel after washing.8
Managing Drug-Resistant Pathogens
Guidelines issued by the CDC in response to the clinical isolation of drug-resistant pathogens18 are listed below. These guidelines are more stringent than those previously published.
If a drug-resistant pathogen, particularly a VISA (vancomycin-intermediate S. aureus) strain, is isolated, the physician and staff should:
notify the state health department and the CDCs Hospital Infections Program (404-639-6400);
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 what surveillance cultures are needed and how to manage the patients discharge. The US Food and Drug Administration (FDA; 301-827-2120) can provide information on investigational antimicrobial agents.
It is important for the health care worker in the ICU to understand how infection occurs, the modes of bacterial transmission, and the prevalent microorganisms involved in the cause of disease. Focused efforts aimed at treating existing infection and preventing the occurrence of nosocomial infection can dramatically improve the care and recovery of patients in the ICU.
Phyllis C. Braun, PhD, is a professor in the Department of Biology, Fairfield University, Fairfield, Conn; and John D. Zoidis, MD, is a contributing writer for RT Magazine.
1. Horan TC, White JW, Jarvis WR, et al. Nosocomial infection surveillance, 1984. MMWR Morb Mortal Wkly Rep. 1986;35:S17-S29.
2. Craven DE, Steger KA. Nosocomial pneumonia in mechanically ventilated adult patients: epidemiology and prevention in 1996. Sem Respir Infect. 1996;11:32-53.
3. George DL. Epidemiology of nosocomial ventilator-associated pneumonia. Infect Control Hosp Epidemiol. 1993;14:163-169.
4. Gross PA, Neu HC, Aswapokee P, et al. Deaths from nosocomial infections: experience in a university hospital and a community hospital. Am J Med. 1980;68:219-223.
5. Leu HS, Kaiser DL, Mori M, Woolson RF, Wenzel RP. Hospital-acquired pneumonia: attributable mortality and morbidity. Am J Epidemiol. 1989;129:1258-1267.
6. Wenzel RP. Hospital-acquired pneumonia: overview of the current state of the art for prevention and control. Eur J Microbiol Infect Dis. 1989;8:56-60.
7. Rello J, Torres A, Ricart M, et al. Ventilator-associated pneumonia by Staphylococcus pneumoniae: comparison of methicillin-resistant and methicillin-sensitive episodes. Am J Respir Crit Care Med. 1994;150:1545-1549.
8. Centers for Disease Control and Prevention (CDC). Guidelines for prevention of nosocomial pneumonia. MMWR Morb Mortal Wkly Rep. 1997;46:1-79.
9. Fagon JY, Chastre J, Domart Y, et al. Nosocomial pneumonia in patients receiving continuous mechanical ventilation: prospective analysis of 52 episodes with use of a protracted specimen brush and quantitative culture techniques. Am Rev Respir Dis. 1989;139:877-884.
10. Finch RG, Woodhead MA. Practical considerations and guidelines for the management of community-acquired pneumonia. Drugs. 1998;55:31-45.
11. Mundy LM, Auwaerter PG, Oldach D, et al. Community-acquired pneumonia: impact of immune status. Am J Respir Crit Care Med. 1995;152:1309-1315.
12. Bernstein JM. Treatment of community-acquired pneumoniatherapeutic options. Chest. 1999;115:9-13.
13. Bayer AS, Scheld WM. Endocarditis and intravascular infections. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennetts Principles and Practice of Infectious Diseases. 5th ed. Philadelphia: Churchill Livingstone; 2000:857-902.
14. Mackowiak PA, Durack DT. Fever of unknown origin. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennetts Principles and Practice of Infectious Diseases. 5th ed. Philadelphia: Churchill Livingstone; 2000:622-633.
15. Mahul PH, Auboyer C, Jospe R, et al. Prevention of nosocomial pneumonia in intubated patients: respective role of mechanical subglottic secretions drainage and stress ulcer prophylaxis. Intensive Care Med. 1992;18:20-25.
16. Valles J, Artigas A, Rello J, et al. Continuous aspiration of subglottic secretions in the prevention of ventilator-associated pneumonia. Ann Intern Med. 1995;122:179-186.
17. Goularte TA, Craven DE. Results of a survey of infection control practices for respiratory therapy equipment. Infect Control. 1986;7:327-330.
18. Centers for Disease Control and Prevention. Interim guidelines for prevention and control of staphylococcal infection associated with reduced susceptibility to vancomycin. MMWR Morb Mortal Wkly Rep. 1997;46:626-628, 635.