Intact skin and mucous membranes provide an effective surface barrier to infection.⁹ These tissues are not merely a mechanical obstacle. The physiologic aspects of skin and mucous membranes provide additional protection. In the skin, the constant turnover of keratinocytes, temperature of the skin, and acid secretion from sebaceous glands inhibits bacterial cell growth. The mucosal surfaces also have developed advanced defense mechanisms to prevent and combat microbial invasion. Specialized epithelial layers provide resistance to infection. In addition, mechanisms such as the mucociliary transport system in the respiratory tract and normal colonic flora in the gastrointestinal tract prevent invasion of organisms. Anything that affects the normal function of these anatomic barriers increases the host’s susceptibility to infection. A skin injury or a burn provides open access to the soft tissues, and antibiotic use disrupts normal colonic flora.¹⁰ Such breakdowns in surface barriers are dealt with by the second line of defenses, the immune system.

Immune Response

The immune system involves complex pathways and many specialized effector responses. The first line of defense is the more primitive and nonspecific innate system, which consists primarily of phagocytic cells and the complement system. The neutrophil is able to rapidly migrate to the source of the infection and engulf and destroy the infecting organisms by phagocytosis. Cytokines, low molecular weight proteins including tumor necrosis factor (TNF), and many interleukins attract and activate neutrophils, and play a significant role in mediating the inflammatory response. In addition, the complement system, when activated, initiates a sequential cascade that also enhances phagocytosis and leads to lysis of pathogens. Neonates, particularly premature infants, have an immature immune system and are helped by the protective agents in human breast milk.11,12 The more specialized, adaptive immune system involves a highly specific response to antigens as well as the eventual production of a variety of humoral mediators.¹³

Humoral and Cell-Mediated Immunity

Specific, adaptive immunity has two major components. The humoral mechanism (B-cell system) is based on bursa cell lymphocytes and plasma cells. The cellular mechanism (T-cell system) consists of the thymic-dependent lymphocytes.¹⁴ The adaptive immune system is an antigen-specific system that is regulated by the lymphocytes. A myriad of receptors on the T-cells that are matched to particular individual antigens create these specific responses. Furthermore, antibody production from B-cells enhances the antigen-specific interaction.

B-cell immunity is provided by antibodies. The first exposure of an antigen leads to the production of IgM antibodies, whereas subsequent exposure to the same antigen results in rapid production of IgG antibodies. Humoral antibodies may neutralize toxins, tag foreign matter to aid phagocytosis (opsonization), or lyse invading cellular pathogens. Plasma cells and non-thymic-dependent lymphocytes that reside in the bone marrow and in the germinal centers and medullary cords of lymph nodes produce the reactive components of this humoral system. These agents account for most of the human immunity against extracellular bacterial species.

The cellular or T-cell component of immunity is based on sensitized lymphocytes located in the subcortical regions of lymph nodes and in the periarterial spaces of the spleen. T-cells are specifically responsible for immunity to viruses, most fungi, and intracellular bacteria. They produce a variety of lymphokines, such as transfer factors, that further activate lymphocytes, chemotactic factors, leukotrienes, and interferons.

Immunodeficiencies

Susceptibility to infection is increased when one of the components of the host defense mechanism is absent, reduced in numbers, or curtailed in function. Some of these derangements may be congenital, although the majority are acquired as a direct result of medications, radiation, endocrine disease, surgical ablation, tumors, or bacterial toxins. Immunodeficiencies from any cause significantly increase the risk of infection both in hospitalized and postoperative patients. Mycotic infections are an increasing problem in immunocompromised pediatric patients.¹⁵

Systemic diseases lead to diminished host resistance. For example, in diabetes mellitus, leukocytes often fail to respond normally to chemotaxis. Therefore, more severe, recurrent, and unusual infections often occur in diabetic patients.¹⁶ In addition, malignancy and other conditions that impair hematopoiesis lead to alterations in phagocytosis, resulting in an increased predilection for infection. Human immunodeficiency virus (HIV) infection in children is another major source of immunodeficiency. Vertical transmission from mother to child is the dominant mode of HIV acquisition among infants and children. Finally, poor nutritional status has adverse effects on immune function owing to a wide variety of negative influences on specific defense mechanisms, including decreased production of antibodies and phagocytic function.¹⁷

In patients with a primary immune defect, susceptibility to a specific infection is based on whether the defect is humoral, cellular, or a combination. Primary immunodeficiencies are rare but important because prompt recognition can lead to life-saving treatment or significant improvement in the quality of life.¹⁸ B-cell deficiencies are associated with sepsis from encapsulated bacteria, especially pneumococcus, Haemophilus influenzae, and meningococcus. Often a fulminating course rapidly ends in death, despite timely therapeutic measures. Although congenital agammaglobulinemia or dysgammaglobulinemia has been widely recognized, other causes of humoral defects include radiation, corticosteroid and antimetabolite therapy, sepsis, splenectomy, and starvation. Chronic granulomatous disease is caused by a deficiency in the respiratory burst action of phagocytes that leads to severe and recurrent bacterial and fungal infections in early childhood. Children with chronic granulomatous disease are prone to develop hepatic abscesses as well as suppurative adenitis of a single node or multiple nodes, both of which may require surgical drainage or excision.¹⁹

T-cell deficiencies are responsible for many viral, fungal, and bacterial infections. Cutaneous candidiasis is a good example of a common infection seen with a T-cell deficiency. DiGeorge syndrome is a developmental anomaly in which both the thymus and the parathyroid glands are deficient, thus increasing the risk for infection and hypocalcemic tetany during infancy.

Antibiotics

The several classes of antibiotics are based on their molecular structure and site of action. The varying classes of antibiotics may be divided into bacteriostatic, which inhibit bacterial growth, and bacteriocidal, which destroy bacteria. The early initiation and correct choice of antibiotics is essential for timely and successful treatment of infections. In addition, it is important to have knowledge of the specific susceptibility patterns in a particular hospital or intensive care unit to direct initial empirical antibiotic therapy. Finally, awareness of interactions and adverse reactions in children from commonly used medications is critical.

The pharmacokinetics and monitoring of drug dosages in infants and children is also important when treating them with antibiotics. The efficacy and safety of many drugs have not been established in the pediatric patient, especially in the newborn.²⁰ Dosages based on pediatric pharmacokinetic data offer the most rational approach. Dosage requirements constantly change as a function of age and body weight. Furthermore, the volume of distribution and half-life of many medicines are often increased in neonates and children compared with adults for a variety of reasons.^21,22 Knowledge of a drug’s pharmacokinetic profile allows manipulation of the dose to achieve and maintain a given plasma concentration.

Newborns usually have extremely skewed drug-distribution patterns. The entire body mass can be considered as if it were a single compartment for the purposes of dose calculations. For the majority of drugs, dose adjustments can be based on plasma drug concentration. Administering a loading dose is advisable when rapid onset of drug action is required. For many drugs, loading doses (milligrams per kilogram) are generally greater in neonates and young infants than in older children or adults.²² However, prolonged elimination of drugs in the neonate requires lower maintenance doses, given at longer intervals, to prevent toxicity. Monitoring serum drug concentrations is useful if the desired effect is not attained or if adverse reactions occur.

The neonate undergoing extracorporeal membrane oxygenation (ECMO) presents a special challenge to drug delivery and elimination. Because the ECMO circuit may bind or inactivate drugs and make them unavailable to the patient, dosing requires careful attention to drug response and serum levels. The pharmacokinetics under these conditions generally include a larger volume of distribution and prolonged elimination, with a return to baseline after decannulation.²³

Prevention of Infections

The most effective way to deal with surgical infectious complications is to prevent their occurrence. The clinician must recognize the variables that increase the risk of infection and attempt to decrease or eliminate them. A summary of the category 1 recommendations published by the Hospital Infection Control Practices Advisory Committee (HICPAC) of the Centers for Disease Control and Prevention is listed in Box 9-1.

Box 9-1

Guidelines for Prevention of Surgical Site Infections

• Treat remote infections before elective surgery

• Do not remove hair preoperatively unless it will interfere with operation

• Adequately control serum blood glucose levels perioperatively

• Require patients to shower or bathe with an antiseptic agent before the operative day

• Use an appropriate antiseptic agent for skin preparation

• Perform a surgical scrub for at least two to five minutes using an appropriate antiseptic

• Administer a prophylactic antimicrobial agent only when indicated

• Administer an antimicrobial agent such that bactericidal concentration of the drug is established in serum and tissues when the incision is made and maintained throughout the operation

• Sterilize all surgical instruments

• Wear a surgical mask

• Wear a cap or hood to fully cover hair on head and face ^a

• Wear sterile gloves ^a

• Use sterile gowns and drapes that are effective barriers when wet

• Handle tissue gently, maintain effective hemostasis, minimize devitalized tissue and foreign bodies, and eradicate dead space at the surgical site

• If drainage is necessary, use closed suction drain

• Protect with a sterile dressing for 24 to 48 hours postoperatively an incision that has been closed primarily

^a Required by the ultrasound Occupational Safety and Health Administration regulations.

From Mangram AJ, Horan TC, Pearson ML, et al. Guideline for Prevention of Surgical Site Infection, 1999. Centers for Disease Control and Prevention (CDC) Hospital Infection Control Practices Advisory Committee. Am J Infect Control 1999;27:97–132.