Neonates

The causative pathogens of neonatal infections are typically acquired around the time of delivery. Thus, empirical antibiotic selection must take into account the importance of these pathogens in neonates (Chapter 103). Among the causes of neonatal sepsis in infants, group B streptococcus is the most common, although intrapartum antibiotic prophylaxis has greatly decreased the incidence of this infection (Chapter 177). Gram-negative enteric organisms acquired from the maternal birth canal, in particular Escherichia coli, are other common causes of neonatal sepsis. Although rare, Listeria monocytogenes is also an important pathogen, insofar as it is intrinsically resistant to cephalosporin antibiotics, which are often used as empirical therapy in young children. All of these organisms can be associated with meningitis in the neonate; therefore, lumbar puncture should always be considered in the setting of bacteremic infections in this age group, and, if meningitis cannot be excluded, antibiotic management should include agents capable of crossing the blood-brain barrier.

Older Children

Antibiotic choices in toddlers and young children were once driven by the high risk of this age group to invasive disease caused by H. influenzae type b (Chapter 186). With the advent of conjugate vaccines against H. influenzae type b, invasive disease has declined dramatically. It is still appropriate to consider the use of antimicrobials that are active against this pathogen, particularly if meningitis is a consideration. Other particularly important pathogens to be considered in this age group include S. pneumoniae, Neisseria meningitidis, and S. aureus. Antimicrobial resistance is commonly exhibited by S. pneumoniae and S. aureus. Strains of S. pneumoniae that are resistant to penicillin and cephalosporin antibiotics are frequently encountered in clinical practice. Similarly, MRSA is highly prevalent in many regions. Resistance of S. pneumoniae as well as MRSA is due to mutations that confer alterations in penicillin binding proteins, the molecular targets of penicillin and cephalosporin activity (see Table 173-1).

Depending on the specific clinical diagnosis, other pathogens that are commonly encountered among older children include Moraxella catarrhalis, nontypable strains of H. influenzae, and Mycoplasma pneumoniae, which cause upper respiratory tract infections and pneumonia; group A streptococcus, which causes pharyngitis, skin and soft tissue infections, osteomyelitis, septic arthritis, and, rarely, bacteremia with toxic shock syndrome; Kingella kingae, which causes bone and joint infections; viridans streptococci and Enterococcus, which cause endocarditis; and Salmonella, which causes enteritis, bacteremia, osteomyelitis, and septic arthritis. This complexity underscores the importance of formulation of a clear clinical diagnosis, including an assessment of the severity of the infection, in concert with knowledge of local susceptibility patterns in the community.

Immunocompromised and Hospitalized Patients

It is important to consider the risks associated with immunocompromising conditions (malignancy, solid organ, or hematopoietic stem cell transplantation) and the risks conferred by conditions leading to prolonged hospitalization (intensive care, trauma, burns). Immunocompromised children are predisposed to develop a wide range of bacterial, viral, fungal, or parasitic infections. Prolonged hospitalization can lead to nosocomial infections, often associated with indwelling lines and catheters and commonly caused by gram-negative enteric organisms. In addition to the usual bacterial pathogens, Pseudomonas aeruginosa and enteric organisms, including E. coli, Klebsiella pneumoniae, Enterobacter, and Serratia, are important considerations as opportunistic pathogens in these settings. Selection of appropriate antimicrobials is challenging because of the diverse causes and scope of antimicrobial resistance exhibited by these organisms. Many strains of enteric organisms have resistance due to extended spectrum β-lactamases (ESBLs) (see Table 173-1). P. aeruginosa encodes proteins that function as efflux pumps to eliminate multiple classes of antimicrobials from the cytoplasm or periplasmic space. In addition to these gram-negative pathogens, infections caused by Enterococcus faecalis and Enterococcus faecium are inherently difficult to treat. These organisms may cause urinary tract infection or infective endocarditis in immunocompetent children and may be responsible for a variety of syndromes in immunocompromised patients, especially in the setting of prolonged intensive care. The emergence of infections caused by vancomycin-resistant Enterococcus (VRE) has further complicated antimicrobial selection in high-risk patients and has necessitated the development of newer antimicrobials that target these highly resistant gram-positive infections. Although experience with many of these newer agents in the management of complex hospitalized pediatric patients is limited, they are important agents to be aware of (described below).

Infections Associated with Medical Devices

A special situation affecting antibiotic use is the presence of an indwelling medical device, such as a venous catheter, ventriculoperitoneal shunt, stent, or other catheter (Chapter 172). In addition to S. aureus, coagulase-negative staphylococci are also a major consideration. Coagulase-negative staphylococci seldom cause serious disease without a risk factor such as an indwelling catheter. Empirical antibiotic regimens must take this risk into consideration. In addition to appropriate antibiotic therapy, removal or replacement of the colonized prosthetic material is commonly required for cure.