Cornerstones of prevention include understanding how infection spreads and using simple precautions.

One of the biggest challenges for a hospital has always been the prevention and spread of disease within a confined setting. A century ago, infectious disease patients were segregated in separate hospitals with individuals having similar diseases clustered on the same floor. In 1910, a cubicle system of isolation was introduced in which patients were placed in multiple-bed wards. Aseptic nursing procedures were aimed at preventing the transmission of disease to other patients and personnel. These careful procedures were so successful that general hospitals were able to incorporate infectious disease patients, ultimately resulting in the closure of many infectious disease hospitals in the 1950s.

Patients are admitted to the hospital for a variety of reasons. Among the most serious are potentially life-threatening bacterial infections. Examples include pneumonia, sepsis, intra-abdominal infection, endocarditis, staphylococcal skin infection, and infections caused by multidrug-resistant pathogens. These microorganisms can cause serious clinical conditions, particularly in the immunocompromised individual.

The routes of transmission of bacterial pathogens, whether direct or indirect, should be considered. The health care practitioner must be aware of any physical contact with the patient that might lead to nosocomial infection, a major source of morbidity and mortality in critically ill hospitalized patients.

Entry of Pathogens
to the Body

Entry through the mouth or nose may lead to:
• Pneumonia (infection of the lung)
• Other respiratory infections such as bronchitis

Entry through the urinary tract opening may lead to:
• Cystitis (infection of the bladder)
• Urethritis (infection of the urethra)
• Pyelonephritis (infection of the kidneys)
• Prostatitis (infection of the prostate)

Entry through breaks in the skin or mucous membranes may lead to:
• Sepsis
• Infections in burn patients
• Postsurgical infections
• Meningitis (infection of the meninges)

Although our ability to care for critically ill patients has improved greatly over the past several decades, the widespread application of techniques such as tracheal intubation and mechanical ventilation in increasingly ill patients has resulted in nosocomial hazards such as ventilator-associated pneumonia. Pneumonia is associated with the greatest mortality among nosocomial (hospital-acquired) infections and with substantial costs of care. Although respiratory organisms are a serious concern, other pathogens that enter through a variety of other routes cannot be ignored.

Transmission of Pathogens
Bacteria reside in a variety of environments including soil, food, water, and many areas in and on human and animal bodies. For invasion to occur, bacteria must be transported to areas within the body that will be conducive to their growth and replication. Most bacteria invade the body via either direct or indirect transmission.

Direct transmission occurs when bacteria are transported to the host through actual contact with the skin or mucous membranes of an infected individual. It can occur during sexual intercourse or any other form of close physical contact.

Indirect transmission occurs when bacteria reside for a period of time in some intermediate environment before reaching the human host. Bacteria are transferred when the host comes into contact with that intermediate environment. Indirect transmission can occur in a variety of ways. For example, it can occur when a host comes into contact with inanimate objects (fomites) that have been contaminated by an infected individual, such as clothing, tabletops, doorknobs, and drinking glasses.

It is also possible for bacteria to be transported indirectly through fine droplets of secretions coughed or sneezed into the air by an infected individual. Pathogens also can be transported into the body through contaminated blood, drugs, food, or water. Finally, indirect transmission can occur when an intermediate animal or insect carries a pathogen from an infected individual to a new host.

The body has several natural openings that allow the passage of pathogens into its tissues. The mouth, nose, and urinary tract are common points of entry. The types of infections that can occur when pathogens enter through these body openings are listed in the Table on page 46.

Bacteria also can pass into the body through areas in which there has been a disruption in the normal defense mechanisms. When there is a weakening of the body’s defenses, an individual is more vulnerable to bacterial infection. For example, the skin and mucous membranes normally form effective protective barriers against infection; however, when there is a break in these barriers such as a cut, burn, wound, or surgical incision, bacteria are allowed to enter, which often leads to infection.

Once the bacteria have entered the body, they must find an environment that will allow them to grow and multiply. When such a body site has been found, the second stage of the infectious disease process, incubation, can occur. During this phase, bacteria will overcome host defenses to the extent that they are able to reproduce effectively. In time, these bacteria may spread to other areas of the body and/or may proliferate to such an extent that they cause harm. Throughout the periods of bacterial invasion and incubation, no symptoms of disease are apparent.

Manifestation of Symptoms
Once pathogenic bacteria have gained entry into the body, they may begin to reproduce rapidly and proliferate until they overwhelm body tissue. As this happens, the disease process enters the prodrome stage and symptoms of infectious disease are manifested. Symptoms are produced by three different mechanisms: colonization of bacteria in body tissues; secretion of bacterial toxins; and reaction of host defenses.

Colonization is one means by which bacteria can cause cellular damage in the host by overpopulating areas of tissue in the body. This overpopulation can prevent the tissues from obtaining necessary oxygen and nutrients, causing local damage to the area of bacterial colonization.

More frequently, bacterial toxins cause the signs and symptoms of infection. Two important types of toxins are exotoxins and endotoxins.

Exotoxins are proteins produced and secreted from certain bacterial cells. They can produce profound effects in the host, such as altering cell membranes, inhibiting cellular protein synthesis, and/or disrupting nervous system function. Exotoxins usually are produced by gram-positive bacteria. While in some cases exotoxins may be distributed throughout the body by the blood, for the most part they produce local effects on body tissues. Clostridium species are the most frequent producers of exotoxins.

Endotoxins are components of the cell walls of gram-negative bacteria. They are liberated, for the most part, when a gram-negative bacterium dies or is destroyed. Endotoxins enter the bloodstream and produce generalized signs and symptoms such as malaise, fever, and chills. Regardless of the bacterium releasing the endotoxin, the effects produced are essentially the same.

Infection may spread in the body and cause disease when the bacteria’s ability to invade tissues is greater than the host’s ability to defend against that invasion. In some cases, pathogens that have a high level of virulence or resistance may persist despite a strong defensive host response. More frequently, compromised host defenses increase susceptibility to infection and allow bacterial pathogens to invade and multiply. An infection that is caused by a pathogen that does not ordinarily cause infection or disease unless it is presented with an opportunity to do so (by weakened host defenses) is called an opportunistic infection.

A number of different factors can cause a patient to become immunocompromised. Any break in the body’s external barriers allows bacteria greater access into areas where they are not normally found. For example, surgery opens the skin, bypassing one important natural barrier to infection. Introduction of catheters, bypass tubes, and prosthetic devices into interior areas of the body may also be accompanied by infection due to the penetration of the body’s external defenses and the introduction of bacteria.

Any condition that weakens an individual can diminish host defenses. Advanced age, nutritional deficiencies, smoking, stress, psychological trauma, and lack of sleep all may weaken defensive responses and increase susceptibility to infection. Preexisting heart and circulatory disorders and acute and chronic illnesses are common in patients with weakened defensive responses. Burn patients are prime examples of immunocompromised patients, as are patients with chronic obstructive pulmonary disease.

Certain therapies can increase the risk of infections. For example, cancer patients may be treated with chemotherapy drugs that kill rapidly dividing cells. These drugs may kill dividing immunologic cells as well; hence, they leave the patient more susceptible to infection. Similarly, antibiotic therapy can, in some cases, destroy the protective normal flora and leave the patient susceptible to superinfection.

The body reacts to invasion and proliferation of bacteria with a variety of defensive responses. While the main purpose and effect of these responses are to restrict the spread of bacteria and to kill bacterial cells, they also can cause many clinically important signs and symptoms. Inflammation is one example of the body’s defensive response. Fever (pyrexia) is another.

The four cardinal signs of inflammation are pain, swelling, redness, and heat. A fifth, “functio laesa” (loss of function), is sometimes described as well. These signs result primarily from two mechanisms: dilation of blood vessels and increased permeability of blood vessel walls.

When blood vessels dilate, they carry increased amounts of blood, protective cells, and plasma proteins to injury sites. Redness and heat result from the accelerated flow of blood that accompanies these dilatory changes. The increased permeability of blood vessel walls results in the escaping of blood proteins and blood cells into the tissues, which causes swelling. This permeability allows increased concentrations of immune system cells and chemicals into the injured tissue, facilitating the elimination of foreign substances.

Fever is another symptom that can result from the body’s defensive responses. Body temperature is regulated by the hypothalamus. Pyrogens cause fever by “resetting” the hypothalamic thermostat higher, forcing the body to reach and maintain this higher temperature. Some pyrogens are secreted by pathogenic invaders; others are manufactured in the body and released from damaged tissues during inflammatory reactions. In addition, nonpathogenic invaders such as some drugs may be pyrogenic. Exogenous pyrogens may act directly to reset the hypothalamic thermostat, or they may act indirectly by causing the release of potent endogenous pyrogens.

While prolonged high fever eventually leads to tissue destruction, limited fever is believed to have some beneficial effects. A rising temperature may augment host defenses by stimulating the proliferation and activity of immune system cells. In addition, a higher body temperature may be less favorable for the growth and multiplication of bacteria.


Types of Infection
A primary infection is the initial infection. It may or may not be the patient’s primary medical condition. Secondary infection occurs when a bacterial infection follows or complicates a preexisting condition.

Mixed infections are caused by two or more pathogens. Accordingly, they can cause two or more distinct clinical problems. This may make it difficult to isolate and identify the causative pathogens. In addition, treatment may be difficult because the two or more organisms may not be susceptible to the same antibiotic. Mixed infections sometimes require two or more antibiotics given at the same time.

Acute infections are characterized by their sudden onset. The course of acute infections is usually relatively short and is sometimes marked by very severe symptoms. Chronic infections, on the other hand, have a prolonged course. Most chronic infections show little change over their slow progression.

A recurrent infection is a repetition of an infection previously experienced by a patient. It is a distinct episode in which the pathogen(s) involved may be the same as or different from those responsible for the initial infection. A recurrent infection is not a relapse. A relapse involves the recurrence of an infection after its apparent cessation. In a relapse, the same pathogen is responsible for the initial infection and the recurrent infection.

A community-acquired infection occurs through normal contact with the general community, as opposed to one acquired in a unique environment such as a hospital or nursing home where the presence of infected individuals is known to contribute to the development of infections.

A nosocomial infection is acquired during hospitalization. This may occur as a result of either exposure to an increased number of pathogenic bacteria or weakened host defenses due to the primary illness, requiring hospitalization.

It is estimated that in the United States alone approximately 6% of people entering a hospital will acquire a nosocomial infection, adding more than $4.5 billion to the price of health care.1 As a result, hospitals are now required to establish an Infection Control Committee responsible for establishing guidelines and protocols designed to minimize the transmission of pathogenic bacteria. Nosocomial infections are so common that they make up at least half of all cases of disease treated in the hospital where they were contracted. The bacteria most commonly implicated in nosocomial infections include:

• Enterococcus species—Enterococci are part of the normal intestinal flora. Some strains are resistant to all conventional antimicrobial drugs. Enterococci are a common cause of nosocomial urinary tract infections as well as wound and blood infections.

• Escherichia coli and other members of the Enterobacteriaceae—E. coli is a part of the normal intestinal flora. It is the most common cause of nosocomial urinary tract infections.

• Pseudomonas species grow in many moist, nutrient-poor environments such as the water in the humidifier of a mechanical ventilator. Pseudomonas species are resistant to many disinfectants and antibiotics. They are a common cause of hospital-acquired pneumonia, urinary tract, and burn wound infections.

• Staphylococcus species—These normal skin organisms can colonize the tips of intravenous catheters. This results in the formation of biofilms, which continuously seed organisms into the bloodstream and increase the likelihood of systemic infection. Staphylococcus aureus is a common cause of nosocomial pneumonia and surgical site infections. Hospital strains are often resistant to a variety of antibiotics.

The relative frequency of different types of nosocomial infections is shown in the figure on page 48.

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Relative Frequency of Different Types of Nosocomial Infection.2

The most important steps in preventing nosocomial infections are first to recognize their occurrence and then to establish policies to prevent their development. In 1996, the Centers for Disease Control and the Hospital Infection Control and Prevention Advisory Committee established a set of guidelines of standardized precautions. The Standard Precautions3,4 include:

• Hand washing—wash hands with soap and water after touching blood, body fluids, secretions, excretions, and contaminated items whether or not gloves are worn.

•Gloves—wear clean, disposable gloves whenever there is possible contact with blood, body fluids, secretions, excretions, mucus membranes, skin wounds, and contaminated items. Change gloves between procedures on the same patient after contact with material that may contain high concentrations of microbes. Remove gloves immediately after use and wash hands thoroughly. Gloves should always be removed in a reverse manner so as not to touch the contaminated surface.

• Mask, eye protection, face shield, gown—when doing a procedure likely to generate splashes or sprays of blood, body fluids, secretions, and excretions, wear a mask and eye protection or a face shield to protect the mucus membranes of the eyes, nose, and mouth. Wear a clean gown and remove the soiled gown as soon as possible, then wash hands.

• Patient-care equipment—handle used patient-care equipment soiled with blood, body fluids, secretions, and excretions in a manner that prevents skin and mucus membrane exposure and contamination and transfer to other patients and environments. Clean and process reusable equipment appropriately. Properly dispose of single-use items.

• Environmental control—use adequate procedures for routine care, cleaning, and disinfecting of environmental surfaces, bed rails, and other frequently touched surfaces.

• Linen—place soiled, reusable items in protective bags to prevent leaking and contamination.

• Occupational health and blood-borne pathogens—discard all needles and sharp objects in rigid, puncture-proof container without touching them or replacing needle caps.

• Patient placement—allocate private rooms for any patient who contaminates the environment or might soil other people and their surroundings.

It is important for the health care worker in a hospital 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 hospitalized patients.

Phyllis C. Braun, PhD, is a professor in the Department of Biology, Fairfield University, Fairfield, Conn.

1. Schaberg DR, Culver DH, Gaynes RP. Major trends in the microbial etiology of nosocomial infection. Am J Med. 1991;91:S725-S755.
2. Emori TG, Gaynes RP. An overview of nosocomial infections, including the role of the microbiology laboratory. Clin Microbiol Rev. 1993;6:428-442.
3. Public Health Services, US Department of Health and Human Services, Centers for Disease Control and Prevention. Guidelines for isolation precautions in hospitals. Infect Control Hosp Epidemiol. 1996;17:53-80.
4. Public Health Services, US Department of Health and Human Services, Centers for Disease Control and Prevention. Guidelines for isolation precautions in hospitals. Am J Infect Control. 1996;24:24-52.