Nosocomial infections in the normal infant nursery are uncommon (fewer than 1 per 100 discharges), whereas in NICUs rates of approximately 20 to 25 per 100 discharges usually are reported. Because the rate of nosocomial infection is related to length of stay, the number of infections per 100 patient-days may better reflect the overall rate. Rates of 0.5 to 1.5 infections per 100 NICU patient-days have been reported in the past few years. In a 2001 report, the point prevalence of nosocomial infections in NICU patients in a multihospital survey, using standardized National Nosocomial Infections Surveillance methods, was 11.4% of 827 patients surveyed, and in another study by the Pediatric Prevention Network, it was 0.86 per 100 NICU patient-days. The rate of infection is considerably higher in low-birth-weight neonates, and the infection rate in any particular unit may be largely a function of the mean birth weight or gestational age of the neonates in the unit and referral patterns for neonatal surgery. Large multihospital surveillance NICU studies report the most frequent sites of nosocomial infections are the bloodstream, followed by infections of the lungs, then gastrointestinal tract, eye, ear, and nose and throat sites. The National Institutes of Child Health and Human Development Neonatal Research Network has reported on a cohort of very low-birth-weight infants (401 to 1,500 g birth weight) admitted to participating centers. Among this selected group of infants, 25% developed a nosocomial bloodstream infection (defined as occurring after 3 days of life) in a 1996 report, and 21% in a 2002 report. In the earlier report, 73% of infections were caused by gram-positive bacterial species (55% of which were coagulase-negative staphylococci) and, similar to many other studies, the rate of infection increased with decreasing birth weight or gestational age; these figures change very little in the later report.

Table 88.1 shows the major causes of late-onset bloodstream infections in neonates. Focal infections that result from
bacteremia (such as meningitis, osteomyelitis, septic and arthritis) and visceral infections usually are caused by the same organisms. Infections that are primarily caused by the spread of organisms from the skin, such as cellulitis, skin abscesses, mastitis, and omphalitis, are likely to be caused by the same organisms. Staphylococcus aureus also is a major cause of these infections and is also a cause of osteomyelitis and septic arthritis. Early-onset infections that are usually caused by maternal vaginal flora most likely are due to group B streptococcus, Escherichia coli, other enteric gram-negative bacilli and, occasionally, Enterococcus species and Listeria monocytogenes. In contrast, late-onset nosocomial infections may be caused by any of these species, but are more likely to be caused by coagulase-negative staphylococci, S. aureus, enterococci, and Candida spp., which are the most common fungi causing infections in the NICU.

The predominate species that cause neonatal nosocomial infections have undergone shifts in the last five decades. In the 1950s, a pandemic of neonatal infections was caused by S. aureus, which abated. In the 1960s, gram-negative rod species increased (especially E. coli) as a cause of maternally transmitted infections, and Pseudomonas aeruginosa was more commonly reported as a cause of hospital-acquired infections. The importance of P. aeruginosa appears to be less today, possibly as a consequence of the better hygienic care of medical equipment. In the early 1970s, group B streptococcus became a major threat worldwide, and it is still a threat, although rates are reduced where perinatal prophylaxis with penicillin has been used. Although early-onset group B streptococcal infections have been reduced by 60% to 80%, the rate of late-onset infections has not been affected. Since the 1980s, organisms more associated with late-onset nosocomial infections, such as coagulase-negative staphylococci and Candida species, have predominated, and along with this has been a shift in the mode of transmission, from primarily maternally transmitted to primarily hospital-acquired.

In addition to the organisms mentioned, a large number of species are occasional causes of nosocomial infections. These include P. aeruginosa, Citrobacter species, Enterobacter species, Salmonella species, Acinetobacter species, Flavobacterium meningosepticum (which is often multiply antibiotic resistant), as well as group A streptococci. These organisms may appear sporadically, but they also may be responsible for clusters of infections caused by a common source of contamination. Since 2000, NICU infections with methicillin-resistant staphylococci (MRSA) have increased. In addition, the colonization of mucosal and skin surfaces with MRSA has emerged as a major problem in NICUs. MRSA often enter the unit via infants contaminated from their mothers, and it is spread on the hands and objects handled by caregivers.

Neonatal viral infections of the herpesvirus family, including cytomegalovirus and herpes simplex virus, generally are transmitted from mother to child. This also is true of human immunodeficiency virus type 1 (HIV-1). Rarely, herpes simplex may be transmitted from an adult to a neonate, and cytomegalovirus and HIV-1 have been transmitted via blood transfusion, but these are no longer considered major problems of nosocomial infection in the newborn nursery. Nosocomial viral infections more likely are caused by respiratory viruses, such as respiratory syncytial virus and adenoviruses, or enterically transmitted viruses, such as rotavirus and enteroviruses. These viruses may be transmitted from mother to infant or carried into the nursery by care personnel or visitors. Generally, viral infections in the nursery reflect viral activity in the community. The onset of respiratory viral infection in neonates may be confusing. Periodic breathing, apnea episodes, and lethargy are common presenting signs, but these signs are nonspecific in premature neonates. Enteroviruses (coxsackieviruses and echoviruses) may infect neonates in the NICU or regular nursery and, again, this reflects the community activity of these viruses. The effects on the infant are variable, from nonspecific febrile episodes to aseptic meningitis to overwhelming multiorgan failure.

Candida species are the major cause of neonatal fungal infections. In addition to C. albicans, the species C. tropicalis, C. parapsilosis, C. lusitaniae, and others also cause neonatal infections. Infections caused by C. krusei are uncommon, but are notable because strains of this species are not susceptible to fluconazole. Candida species are normal flora of the skin and upper respiratory and gastrointestinal tracts. The elimination of normal bacterial flora by antibiotics allows fungi to proliferate abnormally. Premature infants are at risk because of their relatively poor immunologic function, the frequent use of antibiotics, and the use of corticosteroids. Proliferation of Candida on the mucous membranes of the mouth and intertriginous areas is responsible for oral thrush and a common form of diaper dermatitis. It is probably common for infants to become contaminated during birth from a vagina colonized with Candida. Transmission to an infant after birth could occur from the skin of the mother or other caretaker.

Intravenous cannulas appear to be a major risk factor for candidemia and disseminated candidiasis in the neonate. Premature infants who receive hyperalimentation fluid containing lipid emulsion appear especially vulnerable to Candida as well as to coagulase-negative staphylococcal infections. Candida species infections must be suspected in tiny infants (of less than 1,000 g) who have evidence of infection after they have survived the first few weeks of life, and especially those who have been treated with repeated or prolonged courses of broad-spectrum antibiotics for suspected or proven infections.

The clinical manifestations of superficial mucocutaneous candidiasis are characteristic whitish-gray plaques on the mucous membranes of the oral mucosa and the vesicular and pustular lesions of the skin, generally in moist intertriginous areas of the body. The clinical manifestations of candidemia or disseminated candidiasis may include evidence of local infection, such as mucocutaneous lesions or a macular rash, or the symptoms may be nonspecific, such as temperature irregularity, poor feeding, irritability, and changed respiratory pattern. If Candida grows from a culture of the blood without evidence of focal infection in any organ, the diagnosis is candidemia. If candidemia and either local infection in visceral organs, the brain, the cerebrospinal fluid, heart valves, lungs, skeletal tissue, or the vitreous of the eye exist, or if pseudohyphae are seen in the urine or in biopsies of tissue, the diagnosis is disseminated candidiasis.

Invasive fungal infections caused by species other than Candida are uncommon in neonates, because fungal infections such as aspergillosis, cryptococcosis, coccidioidomycosis, blastomycosis, and histoplasmosis generally are contracted from the environment, and neonates are unlikely to have been exposed. In rare instances, in utero exposure may occur. Aspergillus can be present in the hospital environment, often associated with the renovation or construction of a facility, and infants are sufficiently immunocompromised so that invasive infection may occur.

Neonates are subject to superficial cutaneous infection caused by several dermatophytic fungal species such as Epidermophyton, Microsporum, and Trichophyton. When the skin is involved, these species cause ringworm. If treatment is required, griseofulvin can be used. A species from this class, Malassezia furfur, has been isolated frequently from the blood
of tiny infants who had indwelling central vascular catheters. This species seems to thrive on lipid and is associated with the use of intravenous fat emulsions. It is unclear whether antifungal agents are at all effective against M. furfur, but removal of the intravascular line appears to cure the infection.