Antibiotik Therapy Nelson

Kliegman: Nelson Textbook of Pediatrics, 18th ed.
Copyright 2007 Saunders, An Imprint of Elsevier
Section 3 Antibiotic Therapy
Chapter 179 Principles of Antibacterial Therapy

Mark R. Schleiss Antibacterial therapy in infants and children presents many challenges. For some agents there is a paucity of pediatric data regarding pharmacokinetics and optimal dosages; pediatric recommendations are extrapolated from studies in adults. The clinician must consider important differences among various age groups of the pathogenic species responsible for pediatric bacterial infections; age-appropriate antibiotic dosing and toxicities must also be considered. Specific antibiotic therapy is optimally driven by a microbiologic diagnosis, such as isolation of the pathogenic organism from a sterile body site, and supported by antimicrobial susceptibility testing. Much of pediatric infectious diseases practice is based on a clinical diagnosis with empirical use of antibacterial agents before or even without eventual identification of the specific pathogen. Several key considerations must be incorporated in decisions about the appropriate empirical use of antibacterial agents in infants and children. It is important to know the age-appropriate differential diagnosis with respect to likely pathogens. This affects the choice of antimicrobial agent and also the dose, dosing interval, and route of administration (oral vs parenteral). A complete history and physical examination combined with appropriate laboratory and radiographic studies are necessary to identify specific diagnoses, which in turn affects the choice, dosing, and urgency of administration of antimicrobial agents. The vaccination history may reflect reduced risk, but not necessarily elimination of risk, for diseases for which the vaccination series has been completed. The risk for infections is greatly affected by the immunologic status, which may be compromised by immaturity (neonates), underlying disease, and associated treatments (see Chapter 177 ). Infections in immunocompromised children often result from bacteria that are not considered pathogenic in immunocompetent children. The presence of foreign bodies also increases the risk of bacterial infections (see Chapter 178 ). The likelihood of central nervous system (CNS) involvement must be considered because many bacteremic infections in childhood, including Haemophilus influenzae type b, pneumococcus, and meningococcus, carry a significant risk for hematogenous spread to the CNS. The patterns of antimicrobial resistance in the community, and for the potential causative pathogen being empirically treated, must also be considered. Resistance to penicillin and cephalosporin antibiotics is now commonplace among strains of Streptococcus pneumoniae, often necessitating the use of other classes of antibiotics. The striking emergence of community-
acquired methicillin-resistant Staphylococcus aureus (MRSA) infections has further complicated antibiotic choices. Antimicrobial resistance occurs through many modifications of the bacterial genome (Tables 179-1 and 179-2 [1] [2]). Mechanisms include enzyme inactivation of the antibiotic, decreased cell membrane permeability to intracellularly active antibiotics, efflux of antibiotics out of the bacteria, protection or alteration of the antibiotic target site, excessive production of the target site, or passing the antimicrobial site of action. Antibiotic action is related to achieving therapeutic levels at the site of infection. Although measuring the level of antibiotic at the site of infection is not always possible, one may measure the serum level and use it as a surrogate target to achieve the desired effect at the tissue level. Various target serum levels are appropriate for different antibiotic agents and are assessed by the peak and trough serum levels, and the area under the therapeutic drug level curve ( Fig. 179-1 ). These levels are in turn a reflection of the route of administration, drug absorption (IM, PO), volume of distribution, and drug elimination half-life, as well as of drug-drug interactions that might enhance or impede enzymatic inactivation of an antibiotic or result in antimicrobial synergism or antagonism ( Fig. 179-2 ). TABLE 179-1 -- Mechanisms of Resistance to -Lactam Antibiotics I. Alter target site (PBP, penicillin-binding protein) A. Decrease affinity of PBP for -lactam antibiotic 1. Modify existing PBP a. Create mosaic PBP Insert nucleotides obtained from neighboring bacteria, e.g., penicillin-resistant Streptococcus pneumoniae Mutate structural gene of PBP(s), e.g., ampicillin-resistant -lactamase-negative Haemophilus influenzae 2. Import new PBP, e.g., mecA in methicillin-resistant Staphylococcus aureus
II.
Destroy -lactam antibiotic A. Increase production of -lactamase 1. Acquire more efficient promoter a. Mutate existing promoter b. 2. Import new one
Deregulate control of -lactamase production a. Mutate regulator genes, e.g., ampD in stably derepressed Enterobacter cloacae
B.
Modify structure of resident -lactamase 1. Mutate its structural gene, e.g., extended-spectrum -lactamases in Klebsiella pneumoniae C. Import new -lactamase(s) with different spectrum of activity
III. Decrease concentration of -lactam antibiotic inside cell A. Restrict its entry (loss of porins) B. Pump it out (efflux mechanisms)
TABLE 179-2 -- Aminoglycoside-Modifying Enzymes ENZYMES USUAL ANTIBIOTICS MODIFIED COMMON GENERA Phosphorylation APH(2) APH(3)-I APH(3)-III Acetylation AAC(2) AAC(3)-I AAC(6) Adenylation ANT(2) ANT(4) K, T, GE, PS K, T, A SA G T, G K, T, A PR E, PS E, PS E, PS, SA K, T, G K K, A SA, SR E, PS, SA, SR E, PS, SA, SR
AAC(3)-III, -IV, OR-V K, T, G
A, amikacin; AAC, aminoglycoside acetyltransferase; ANT, aminoglycoside nucleotidyltransferase; APH, aminoglycoside phosphotransferase; E, Enterobacteriaceae; G, gentamicin; K, karamycin; PR, Providencia-Proteus; PS, pseudomonids; SA, staphylococci; SR, streptococci; T, tobramycin.
AGE- AND RISK-SPECIFIC USE OF ANTIBIOTICS IN CHILDREN. Neonates.
The causative pathogens of neonatal infections are typically acquired around the time of delivery. Thus, empiric antibiotic selection must take into account the importance of these pathogens in neonates (see Chapter 109 ). 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 (see Chapter 183 ). 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, and is resistant to cephalosporin antibiotics. All of these organisms can be associated with meningitis in the neonate; therefore, 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 unique susceptibility of this age group to invasive disease caused by H. influenzae type b (see Chapter 192 ). With the advent of conjugate vaccines for 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, meningococcus, 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, MRSAs are 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 179-1 ). Depending on the specific diagnosis, other pathogens that are commonly encountered among older children include Moraxella catarrhalis, nontypable strains of H. influenzae, and Mycoplasma pneumoniae, which cause otorhinolaryngologic infections and pneumonia; group A streptococcus, which causes pharyngitis, skin and soft tissue infections, osteomyelitis, and septic arthritis; 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) or with settings where prolonged hospitalization predisposes to nosocomial infections (intensive care, burns). In addition to the usual bacterial pathogens, Pseudomonas aeruginosa and enteric organisms, including Escherichia 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 -lactamases (ESBLs) (see Table 179-1 ). 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, both E. faecalis and E. 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 occurrence of strains of 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 grampositive infections, although experience with many of these newer agents in the management of complex hospitalized pediatric patients is limited.
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 (see Chapter 178 ). 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. Empiric 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.
ANTIBIOTICS COMMONLY USED IN PEDIATRIC PRACTICE ( TABLE 179-3 ) Penicillins.
Although there has been ever-increasing emergence of resistance to penicillins, these agents remain valuable and are commonly used for management of many pediatric infectious diseases.
TABLE 179-3 -- Antibacterial Medications (Antibiotics) INDICATIONS DRUG (TRADE NAMES, (MECHANISM OF FORMULATIONS) ACTION) AND DOSING Amikacin sulfate Amikin. Injection: 50 mg/mL, 250 mg/ml. Aminoglycoside antibiotic active against gram-negative bacilli, especially Escherichia coli, Klebsiella, Proteus, Enterobacter, Serratia, and Pseudomonas. Neonates: Postnatal age 7 days: 1,2002,000 g: 7.5 mg/kg q 1218 hr IV or IM; >2,000 g: 10 mg/kg q 12 hr IV or IM;postnatal age >7
COMMENTS Cautions: Anaerobes, Streptococcus (including S. pneumoniae) are resistant. May cause ototoxicity and nephrotoxicity. Monitor renal function. Drug eliminated renally. Administered IV over 3060 min. Drug interactions: May potentiate other ototoxic and nephrotoxic drugs. Target serum
DRUG (TRADE NAMES, FORMULATIONS)
INDICATIONS (MECHANISM OF ACTION) AND DOSING days: 1,2002,000 g IV or IM: 7.5 mg/kg q 812 hr IV or IM; >2,000 g: 10 mg/kg q 8 hr IV or IM. Children: 1525 mg/kg/24 hr divided q 812 hr IV or IM. Adults: 15 mg/kg 24 hr divided q 812 hr IV or IM.
COMMENTS concentrations: Peak 25 40 mg/L;trough <10 mg/L.
Amoxicillin Amoxil, Polymox. Capsule: 250,500 mg. Tablet:chewable: 125,250 mg. Suspension: 125 mg/5 mL, 250 mg/5 mL. Drops: 50 mg/mL.
Penicillinasesusceptible -lactam: gram-positive pathogens except Staphylococcus, Salmonella, Shigella, Neisseria, E. coli, and Proteus mirabilis. Children: 2050 mg/kg/24 hr divided q 812 hr PO. Higher dose of 8090 mg/kg 24 hr PO for otitis media. Adults: 250500 mg q 812 hr PO. Uncomplicated gonorrhea: 3 g with 1 g probenecid PO.
Cautions: Rash, diarrhea, abdominal cramping. Drug eliminated renally. Drug interaction: Probenecid.
Amoxicillin-clavulanate Augmentin. Tablet: 250,500,875 mg. Tablet, chewable: 125,200,250,400 mg.
-Lactam (amoxicillin) and lactamase inhibitor (clavulanate) enhances amoxicillin activity against pencillinase-
Cautions: drug dosed on amoxicillin component. May cause diarrhea, rash. Drug eliminated renally. Drug interaction: Probenecid.
DRUG (TRADE NAMES, FORMULATIONS) Suspension: 125 mg/5 mL, 200 mg/5 mL, 250 mg/5 mL, 400 mg/5 mL.
INDICATIONS (MECHANISM OF ACTION) AND DOSING producing bacteria. S. aureus (not methicillin-resistant organism), Streptococcus, Haemophilus influenzae, Moraxella catarrhalls, E. coli, Klebsiella, Bacteroides fragilis. Neonates: 30 mg/kg/24 hr divided q 12 hr PO. Children: 2045 mg/kg 24 hr divided q 812 hr PO. Higher dose 8090 mg/kg/24 hr PO for otitis media.
COMMENTS Comment: Higher dose may be active against penicillin tolerant/resistant S. pneumoniae.
Ampicillin Polycillin, Omnipen. Capsule: 250,500 mg. Suspension: 125 mg/5 mL, 250 mg/5 mL, 500 mg/5 mL. Injection.
-Lactam with same spectrum of antibacterial activity as amoxicillin. Neonates: Postnatal age 7 days 2,000 g: 50 mg/kg/24 hr IV or IM q 12 hr (meningitis: 100 mg/kg/24 hr divided q 12 hr IV or IM); >2,000 g: 75 mg/kg/24 hr divided q 8 hr IV or IM (meningitis: 150 mg/kg/24 hr divided q 8 hr IV or IM). Postnatal age >7 days <1,200 g: 50 mg/kg/24 hr IV or IM q 12 hr (meningitis: 100 mg/kg/24 hr divided q
Cautions: Less bioavailable than amoxicillin causing greater diarrhea. Drug interaction: Probenecid.
INDICATIONS (MECHANISM OF ACTION) AND DOSING 12 hr IV or IM);1,200 2,000 g: 75 mg/kg/24 hr divided q 8 hr IV or IM (meningitis: 150 mg/kg/24 hr divided q 8 hr IV or IM); >2,000 g: 100 mg/kg/24 hr divided q 6 hr IV or IM (meningitis: 200 mg/kg/24 hr divided q 6 hr IV or IM). Children: 100200 mg/kg/24 hr divided q 6 hr IV or IM (meningitis: 200400 mg/kg/24 hr divided q 46 hr IV or IM). Adults: 250500 mg q 48 hr IV or IM.
COMMENTS
Ampicillin-sulbactam Unasyn. Injection.
-Lactam (ampicillin) -lactamase inhibitor (sulbactam) enhances ampicillin activity against penicillinaseproducing bacteria: S. aureus, Streptococcus, H. influenzae, M. catarrhalis, E. coli, Klebsiella, B. fragilis. Children: 100200 mg/kg/24 hr divided q 48 hr IV or IM. Adults: 12 g q 68 hr IV or IM (max daily dose: 8 g).
Cautions: Drug dosed on ampicillin component. May cause diarrhea, rash. Drug eliminated renally. Note: Higher dose may be active against penicillintolerant/resistant S. pneumoniae. Drug interaction: Probenecid.
Azithromycin
Azalide antibiotic with activity against
Note: very long half-life permitting once-daily dosing.
DRUG (TRADE NAMES, FORMULATIONS) Zithromax. Tablet: 250 mg. Suspension: 100 mg/5 mL, 200 mg/5 mL.
INDICATIONS (MECHANISM OF ACTION) AND DOSING S. aureus, Streptococcus, H. influenzae, Mycoplasma, Legionella, Chlamydia trachomatis.
COMMENTS
No metabolic-based drug interactions (unlike erythomycin and clarithromycin), limited gastrointestinal distress. Shorter-course regimens (e.g., 13 days) under investigation. Children: 10 mg/kg PO Three-day, therapy (10 on day 1 (max: 500 mg) mg/kg/increasing frequency followed by 5 mg/kg (not for streptococcus PO q 24 hr for pharyngitis). 4 days. Group A Streptococcus pharyngitis: 12 mg/kg/24 hr PO (max: 500 mg) for 5 days. Adults: 500 mg PO day 1 followed by 250 mg for 4 days. Uncomplicated C. trachomatis infection: single 1 g dose PO.
Aztreonam Azactam. Injection.
-Lactam (monobactam) antibiotic with activity against gram-negative aerobic bacteria, Enterobacteriaceae, and Pseudomonas aeruginosa. Neonates: Postnatal age 7 days 2,000 g: 60 mg/kg/24 hr divided q 12 hr IV or IM; >2,000 g: 90 mg/kg/24 hr divided q 8 hr IV or IM;postnatal age >7 days <1,200 g: 60 mg/kg/24 hr divided q
Cautions: Rash, thrombophlebitis, eosinophilia. Renally eliminated. Drug interaction: Probenecid.
INDICATIONS (MECHANISM OF ACTION) AND DOSING 12 hr IV or IM; 1,200 2,000 g: 90 mg/kg/24 hr divided q 8 hr IV or IM; >2,000 g: 120 mg/kg/24 hr divided q 68 hr IV or IM. Children: 90120 mg/kg/24 hr divided q 68 hr IV or IM. For cystic fibrosis up to 200 mg/kg/24 hr IV. Adults: 12 g IV or IM q 812 hr (max 8 g/24 hr).
COMMENTS
Carbenicillin Geopen Injection. Geocillin oral tablet.
Extended-spectrum penicillin (remains susceptible to penicillinase destruction) active against Enterobacter, indole-positive Proteus, and Pseudomonas. Neonates: Postnatal age 7 days 2,000 g: 225 mg/kg/24 hr divided q 8 hr IV or IM; >2,000 g: 300 mg/kg/24 hr divided q 6 hr IV or IM; >7 days: 300400 mg/kg/24 hr divided q 6 hr IV or IM. Children: 400600 mg/kg/24 hr divided q 46 hr IV or IM.
Cautions: Painful given intramuscularly; rash;each gram contains 5.3 mEq sodium. Interferes with platelet aggregation at high doses, increases in liver transaminase levels. Renally eliminated. Oral tablet for treatment of urinary tract infection only. Drug interaction: Probenecid.
Cefaclor Ceclor.
2nd generation cephalosporin active against S. aureus,
Cautions: -Lactam safety profile (rash, eosinophilia) with high
DRUG (TRADE NAMES, FORMULATIONS) Capsule: 250,500 mg. Suspension: 125 mg/5 mL, 187 mg/5 mL, 250 mg/5 mL, 375 mg/5 mL.
INDICATIONS (MECHANISM OF ACTION) AND DOSING Streptococcus including S. pneumoniae, H. influenzae, E. coli, Klebsiella, and Proteus. Children: 2040 mg/kg/24 hr divided q 812 hr PO (max dose: 2 g). Adults: 250500 mg q 68 hr PO.
COMMENTS incidence of serum sickness reaction. Renally eliminated. Drug interaction: Probenecid.
Cefadroxil Duricef, Ultracef. Capsule: 500 mg. Tablet: 1,000 mg. Suspension: 125 mg/5 mL, 250 mg/5 mL, 500 mg/5 mL.
First-generation cephalosporin active against S. aureus, Streptococcus, E. coli, Klebsiella, and Proteus. Children: 30 mg/kg/24 hr divided q 12 hr PO (max dose: 2 g). Adults: 250500 mg q 812 hr PO.
Cautions: -Lactam safety profile (rash, eosinophilia). Renally eliminated. Long half-life permits q 1224 hr dosing. Drug interaction: Probenecid.
Cefazolin Ancef, Kefzol. Injection.
1st generation cephalosporin active against S. aureus, Streptococcus, E. coli, Klebsiella, and Proteus. Neonates: Postnatal age 7 days 40 mg/kg/24 hr divided q 12 hr IV or IM; >7 days 4060 mg/kg/24 hr divided q 8 hr IV or IM. Children: 50100 mg/kg/24 hr divided q
Caution: -Lactam safety profile (rash, eosinophilia). Renally eliminated. Does not adequately penetrate CNS. Drug interaction: Probenecid.
INDICATIONS (MECHANISM OF ACTION) AND DOSING 8 hr IV or IM. Adults: 0.52 g q 8 hr IV or IM (max dose: 12 g/24 hr).
COMMENTS
Cefdinir Omnicef. Capsule: 300 mg. Oral suspension: 125 mg/5 mL.
Extended-spectrum, semi-synthetic cephalosporin. Children 6 mo12 yr: 14 mg/kg/24 hr in 1 or 2 doses PO (max: 600 mg/24 hr). Adults: 600 mg q 24 hr PO.
Cautions: Reduce dosage in renal insufficiency (creatinine clearance <60 mL/min). Avoid taking concurrently with ironcontaining products and antacids because absorption is markedly decreased; take at least 2 hr apart. Drug interaction: Probenecid.
Cefepime Maxipime. Injection.
Expanded-spectrum, 4th generation cephalosporin active against many grampositive and gramnegative pathogens, including many multidrug-resistant pathogens. Children: 100150 mg/kg/24 hr q 812 hr IV or IM. Adults: 24 g/24 hr q 12 hr IV or IM.
Adverse events: Diarrhea, nausea, vaginal candidiasis Cautions: -Lactam safety profile (rash, eosinophilia). Renally eliminated. Drug interaction: Probenecid.
Cefixime Suprax. Tablet: 200,400 mg. Suspension: 100 mg/5 mL.
3rd generation cephalosporin active against Streptococcus, H. influenzae, M. catarrhalis, N. gonorrhoeae, S. marescens, and P.
Cautions: -Lactam safety profile (rash, eosinophilia). Renally eliminated. Does not adequately penetrate CNS. Drug interaction:
INDICATIONS (MECHANISM OF ACTION) AND DOSING vulgaris. No antistaphylococcal or antipseudomonal activity. Children: 8 mg/kg/24 hr divided q 1224 hr PO. Adults: 400 mg/24 hr divided q 1224 hr PO.
COMMENTS Probenecid.
Cefoperazone sodium Cefobid. Injection.
3rd generation cephalosporin active against many grampositive and gramnegative pathogens. Neonates: 100 mg/kg/24 hr divided q 12 hr IV or IM. Children: 100150 mg/kg/24 hr divided q 812 hr IV or IM. Adults: 24 g/24 hr divided q 812 hr IV or IM (max dose: 12 g/24 hr).
Cautions: Highly protein bound cephalosporin with limited potency reflected by weak antipseudomonal activity. Variable gram-positive activity. Primarily hepatically eliminated in bile. Drug interaction: Disulfiram-like reaction with alcohol.
Cefotaxime sodium Claforan. Injection.
3rd generation cephalosporin active against gram-positive and gram-negative pathogens. No antipseudomonal activity. Neonates: 7 days: 100 mg/kg/24 hr divided q 12 hr IV or IM; >7 days: <1,200 g 100 mg/kg/24 hr divided q 12 hr IV or IM;
Cautions: -Lactam safety profile (rash, eosinophilia). Renally eliminated. Each gram of drug contains 2.2 mEq sodium. Active metabolite. Drug interaction: Probenecid.
INDICATIONS (MECHANISM OF ACTION) AND DOSING >12,000 g: 150 mg/kg/24 hr divided q 8 hr IV or IM. Children: 150 mg/kg/24 hr divided q 68 hr IV or IM (meningitis: 200 mg/kg/24 hr divided q 68 hr IV). Adults: 12 g q 812 hr IV or IM (max: 12 g/24 hr).
COMMENTS
Cefotetan disodium Cefotan. Injection.
2nd generation cephalosporin active against S. aureus, Streptococcus, H. influenzae, E. coli, Klebsiella, Proteus, and Bacteroides. Inactive against Enterobacter. Children: 4080 mg/kg/24 hr divided IV or IM q 12 hr. Adults: 24 g/24 hr divided q 12 hr IV or IM (max: 6 g/24 hr).
Cautions: Highly protein-bound cephalosporin, poor CNS penetration; -Lactam safety profile (rash, eosinophilia), disulfiramlike reaction with alcohol. Renally eliminated (20% in bile).
Cefoxitin sodium Mefoxin. Injection.
2nd generation cephalosporin active against S. aureus, Streptococcus, H. influenzae, E. coli, Klebsiella, Proteus, and Bacteroides. Inactive against Enterobacter. Neonates: 70100 mg/kg/24 hr divided q 812 hr IV or IM.
Cautions: Poor CNS penetration; -Lactam safety profile (rash, eosinophilia). Renally eliminated. Painful given intramuscularly. Drug interaction: Probenecid.
INDICATIONS (MECHANISM OF ACTION) AND DOSING Children: 80160 mg/kg/24 hr divided q 68 hr IV or IM. Adults: 12 g q 68 hr IV or IM (max dose: 12 g/24 hr).
COMMENTS
Cefpodoxime proxetil Vantin. Tablet: 100 mg, 200 mg. Suspension: 50 mg/5 mL, 100 mg/5 mL.
3rd generation cephalosporin active against S. aureus, Streptococcus, H. influenzae, M. catarrhalis, N. gonorrhoeae, E. coli, Klebsiella, and Proteus. No antipseudomonal activity. Children: 10 mg/kg/24 hr divided q 12 hr PO. Adults: 200800 mg/24 hr divided q 12 hr PO (max dose: 800 mg/24 hr). Uncomplicated gonorrhea: 200 mg PO as single-dose therapy.
Cautions: -Lactam safety profile (rash, eosinophilia). Renally eliminated. Does not adequately penetrate CNS. Increased bioavailability when taken with food. Drug interaction: Probenecid;antacids and H-2 receptor antagonists may decrease absorption.
Cefprozil Cefzil. Tablet: 250,500 mg. Suspension: 125 mg/5 mL, 250 mg/5 mL.
2nd generation cephalosporin active against S. aureus, Streptococcus, H. Influenzae, E. coli, M. catarrhalis, Klebsiella, and Proteus. Children: 30 mg/kg/24 hr divided q 812 hr PO. Adults: 5001,000
Cautions: -Lactam safety profile (rash, eosinophilia). Renally eliminated. Good bioavailability; food does not affect bioavailability. Drug interaction: Probenecid.
INDICATIONS (MECHANISM OF ACTION) AND DOSING mg/24 hr divided q 12 hr PO (max dose: 1.5 g/24 hr).
COMMENTS
Ceftazidime Fortaz, Ceptaz, Tazicer, Tazidime. Injection.
3rd generation cephalosporin active against gram-positive and gram-negative pathogens including Pseudomonas aeruginosa. Neonates: Postnatal age 7 days: 100 mg/kg/24 hr divided q 12 hr IV or IM; >7 dyas 1,200 g: 100 mg/kg/24 hr divided q 12 hr IV or IM; >1,200 g: 150 mg/kg/24 hr divided q 8 hr IV or IM. Children: 150 mg/kg/24 hr divided q 8 hr IV or IM (meningitis: 150 mg/kg/24 hr IV divided q 8 hr). Adults: 12 g q 812 hr IV or IM (max: 812 g/24 hr).
Cautions: -Lactam safety profile (rash, eosinophilia). Renally eliminated. Increasing pathogen resistance developing with longterm, widespread use. Drug interaction: Probenecid.
Ceftiaoxime Cefizox. Injection.
3rd generation cephalosporin active against gram-positive and gram-negative pathogens. No antipseudomonal activity. Children: 150 mg/kg/24 hr divided q 68 hr IV or IM.
Cautions: -Lactam safety profile (rash, eosinophilia). Renally eliminated. Drug interaction: Probenecid.
INDICATIONS (MECHANISM OF ACTION) AND DOSING Adults: 12 g q 68 hr IV or IM (max dose: 12 g/24 hr).
COMMENTS
Ceftriaxone sodium Rocephin. Injection.
3rd generation cephalosporin active against gram-positive and gram-negative pathogens. No antipseudomonal activity. Very potent and -lactamase stable. Neonates: 5075 mg/kg q 24 hr IV or IM. Children: 5075 mg/kg q 24 hr IV or IM (meningitis: 75 mg/kg dose 1 then 80100 mg/kg/24 hr divided q 1224 hr IV or IM). Adults: 12 g q 24 hr IV or IM (max dose: 4 g/24 hr).
Cautions: -Lactam safety profile (rash, eosinophilia). Eliminated via kidney (3365%) and bile; can cause sludging. Long half-life and dosedependent protein binding favors q 24 hr rather than q 12 hr dosing. Can add 1% lidocaine for IM injection.
Cefuroxime (cefuroxime axetil for oral administration) Ceftin, Kefurox, Zinacef. Injection. Suspension: 125 mg/5 mL. Tablet: 125,250,500 mg.
2nd generation cephalosporin active against S. aureus, Streptococcus, H. influenzae, E. coli, M. catarrhalis, Klebsiella, and Proteus. Neonates: 40100 mg/kg/24 hr divided q 12 hr IV or IM. Children: 200240 mg/kg/24 hr divided q 8 hr IV or IM;PO administration:
Cautions: -Lactam safety profile (rash, eosinophilia). Renally eliminated. Food increases PO bioavailability. Drug interaction: Probenecid.
INDICATIONS (MECHANISM OF ACTION) AND DOSING 2030 mg/kg/24 hr divided q 8 hr PO. Adults: 7501,500 mg q 8 hr IV or IM (max dose: 6 g/24 hr).
COMMENTS
Cephalexin Keflex, Keftab. Capsule: 250,500 mg Tablet: 500 mg, 1 g. Suspension: 125 mg/5 mL, 250 mg/5 mL, 100 mg/mL drops.
1st generation cephalosporin active against S. aureus, Streptococcus, E. coli, Klebsiella, and Proteus. Children: 25100 mg/kg/24 hr divided q 68 hr PO. Adults: 250500 mg q 6 hr PO (max dose: 4 g/24 hr).
Cephradine Velosef Capsule: 250,500 mg. Suspension: 125 mg/5 mL, 250 mg/5 mL.
1st generation cephalosporin active against S. aureus, Streptococcus, E. coli, Klebsiella, and Proteus. Children: 50100 mg/kg/24 hr divided q 612 hr PO. Adults: 250500 mg q 612 hr PO (max dose: 4 g/24 hr).
Chloramphenicol Chloromycetin. Injection. Capsule: 250 mg. Ophthalmic, otic solutions.
Broad-spectrum protein sythesis inhibitor active against many grampositive and gramnegative bacteria, Salmonella, vancomycin-
Cautions: Gray-baby syndrome (from too-high dose in neonate), bone marrow suppression aplastic anemia (monitor hematocrit, free serum iron).
DRUG (TRADE NAMES, FORMULATIONS) Ointment.
INDICATIONS (MECHANISM OF ACTION) AND DOSING anaerobes, resistant Enterococcus faecium, Bacteroides, other Mycoplasma, Chlamydia, and Rickettsia; Pseudomonas usually resistant. Neonates: Initial loading dose 20 mg/kg followed 12 hr later by: postnatal age 7 days: 25 mg/kg/24 hr q 24 hr IV; >7 days: 2,000 g: 25 mg/kg/24 hr q 24 hr IV; >2,000 g: 50 mg/kg/24 hr divided q 12 hr IV. Children: 5075 mg/kg/24 hr divided q 68 hr IV or PO (meningitis: 75100 mg/kg/24 hr IV divided q 6 hr). Adults: 50 mg/kg/24 hr divided q 6 hr IV or PO (max dose: 4 g/24 hr).
COMMENTS Drug interactions: Phenytoin, phenobarbital, rifampin may decrease levels. Target serum concentrations: Peak 20 30 mg/L;trough 510 mg/L.
Ciprofloxacin Cipro. Tablet: 100,250,500,750 mg. Injection. Ophthalmic solution and ointment. Otic suspension. Oral suspension: 250 and
Quinolone antibiotic active against P. aeruginosa, Serratia, Enterobacter, Shigella, Salmonella, Campylobacter, Neisseria gonorrhoeae, H. influenzae, M. catarrhalis, some S. aureus, and Streptococcus. Neonates: 10 mg/kg q
Cautions: Concerns of joint destruction in juvenile animals not seen in humans; tendonitis, superinfection, dizziness, confusion, crystalluria, some photosensitivity. Drug interactions: Theophylline, magnesium-, aluminum-, or calcium-containing antacids, sucralfate,
DRUG (TRADE NAMES, FORMULATIONS) 500 mg/5 mL.
INDICATIONS (MECHANISM OF ACTION) AND DOSING 12 hr PO or IV. Children: 1530 mg/kg/24 hr divided q 12 hr PO or IV;cystic fibrosis: 2040 mg/kg/24 hr divided q 812 hr PO or IV. Adults: 250750 mg q 12 hr; 200400 mg IV q 12 hr PO (max dose: 1.5 g/24 hr).
COMMENTS probenecid, warfarin, cyclosporine.
Clarithromycin Biaxin. Tablet: 250,500 mg. Suspension: 125 mg/5 mL, 250 mg/5 mL.
Macrolide antibiotic with activity against S. aureus, Streptococcus, H. influenzae, Legionella, Mycoplasma, and C. trachomatis. Children: 15 mg/kg/24 hr divided q 12 hr PO. Adults: 250500 mg q 12 hr PO (max dose: 1 g/24 hr).
Cautions: Adverse events less than erythromycin; gastrointestinal upset, dyspepsia, nausea, cramping. Drug interactions: Same as erythromycin: astemizole carbamazepine, terfenadine cyclosporine, theophylline, digoxin, tacrolimus. Cautions: Diarrhea, nausea, C. difficile-associated colitis, rash. Administer slow IV over 3060 min. Topically active as an acne treatment.
Clindamycin Cleocin. Capsule: 75,150,300 mg. Suspension: 75 mg/5 mL. Injection. Topical solution, lotion, and gel. Vaginal cream.
Protein synthesis inhibitor active against most grampositive aerobic and anaerobic cocci except Enterococcus. Neonates: Postnatal age 7 days <200 g; 10 mg/kg/24 hr divided q 12 hr IV or IM; >2,000 g: 15 mg/kg/24 hr divided q 8 hr IV or IM; >7 days <1,200 g: 10 mg/kg/24 hr IV or
INDICATIONS (MECHANISM OF ACTION) AND DOSING IM divided q 12 hr; 1,2002,000 g: 15 mg/kg/24 hr divided q 8 hr IV or IM; >2,000 g: 20 mg/kg/24 hr divided q 8 hr IV or IM. Children: 1040 mg/kg/24 hr divided q 68 hr IV, IM, or PO. Adults: 150600 mg q 68 hr IV, IM, or PO (max dose: 5 g/24 hr IV or IM or 2 g/24 hr PO).
COMMENTS
Cloxacillin sodium Tegopen. Capsule: 250,500 mg. Suspension: 125 mg/5 mL.
Penicillinase-resistant penicillin active against S. aureus and other gram-positive cocci except Enterococcus and coagulase-negative staphylococci. Children: 50100 mg/kg/24 hr divided q 6 hr PO. Adults: 250500 mg q 6 hr PO (max dose: 4 g/24 hr).
Cautions: -Lactam safety profile (rash, eosinophilia). Primarily hepatically eliminated; requires dose reduction in renal disease. Food decreases bioavailabilty. Drug interaction: Probenecid.
Co-trimoxazole (trimethoprimsulfamethoxazole; TMPSMZ) Bactrim, Cotrim, Septra, Sulfatrim. Tablet: SMZ 400 mg and TMP 80 mg. Tablet DS: SMZ 800 mg
Antibiotic combination with sequential antagonism of bacterial folate synthesis with broad antibacterial activity: Shigella, Legionella, Nocardia, Chlamydia, Pneumocystis carinii. Dosage based on TMP
Cautions: Drug dosed on TMP (trimethoprim) component. Sulfonamide skin reactions: rash, erythema multiforme, StevensJohnson syndrome, nausea, leukopenia. Renal and hepatic elimination; reduce dose
DRUG (TRADE NAMES, FORMULATIONS) and TMP 160 mg. Suspension: SMZ 200 mg and TMP 40 mg/5 mL. Injection.
INDICATIONS (MECHANISM OF ACTION) AND DOSING component. Children: 620 mg TMP/kg/24 hr or IV divided q 12 hr PO. P. carinii pneumonia: 1520 mg TMP/kg/24 hr divided q 12 hr PO or IV. P. carinii prophylaxis: 5 mg TMP/kg/24 hr or 3 times/wk PO. Adults: 160 mg TMP q 12 hr PO.
COMMENTS in renal failure. Drug interactions: Protein displacement with warfarin, possibly phenytoin, cyclosporine.
Demeclocycline Declomycin. Tablet: 150,300 mg. Capsule: 150 mg.
Tetracycline active against most grampositive cocci except Enterococcus, many gram-negative bacilli, anaerobes, Borrelia burgdorferi (Lyme disease), Mycoplasma, and Chlamydia. Children: 812 mg/kg/24 hr divided q 612 hr PO. Adults: 150 mg PO q 68 hr. Syndrome of inappropriate antidiuretic hormone secretion: 9001,200 mg/24 hr or 1315 mg/kg/24 hr divided q 68 hr PO with dose reduction based on response to 600900 mg/24 hr.
Cautions: Teeth staining, possibly permanent (if administered <8 yr of age) with prolonged use; photosensitivity, diabetes insipidus, nausea, vomiting, diarrhea, superinfections. Drug interactions: Aluminum-, calcium-, magnesium-, zinc- and iron-containing food, milk, dairy products may decrease absorption.
DRUG (TRADE NAMES, FORMULATIONS) Dicloxacillin Dynapen, Pathocil. Capsule: 125,250,500 mg. Suspension: 62.5 mg/5 mL.
INDICATIONS (MECHANISM OF ACTION) AND DOSING Penicillinase-resistant penicillin active against S. aureus and other gram-positive cocci except Enterococcus and coagulase-negative staphylococci. Children: 12.5100 mg/kg/24 hr divided q 6 hr PO. Adults: 125500 mg q 6 hr PO.
COMMENTS Cautions: -Lactam safety profile (rash, eosinophilia). Primarily renally (65%) and bile (30%) elimination. Food may decrease bioavailability. Drug interaction: Probenecid.
Doxycycline Vibramycin, Doxy. Injection. Capsule: 50,100 mg. Tablet: 50,100 mg. Suspension: 25 mg/5 mL. Syrup: 50 mg/5 mL.
Tetracycline antibiotic active against most gram-positive cocci except Enterococcus, many gram-negative bacilli, anaerobes, Borrelia burgdorferi (Lyme disease), Mycoplasma, and Chlamydia. Children: 25 mg/kg/24 hr divided q 1224 hr PO or IV (max dose: 200 mg/24 hr). Adults: 100200 mg/24 hr divided q 1224 hr PO or IV.
Cautions: Teeth staining, possibly permanent (<8 yr of age) with prolonged use; photosensitivity, nausea, vomiting, diarrhea, superinfections. Drug interactions: Aluminum-, calcium-, magnesium-, zinc-, iron-, kaolin-, and pectincontaining products, food, milk, dairy products may decrease absorption. Carbamazepine, rifampin, barbiturates may decrease half-life. Cautions: Motilin agonist leading to marked abdominal cramping, nausea, vomiting, diarrhea. Associated with hypertrophic pyloric stenosis in young infants.
Erythromycin E-Mycin, Ery-Tab, Ery-C, Ilosone. Estolate 125,500 mg. Tablet EES:200 mg. Tablet base: 250,333,500
Bacteriostatic macrolide antibiotic most active against gram-positive organisms, Corynebacterium diphtheriae, and Mycoplasma
DRUG (TRADE NAMES, FORMULATIONS) mg. Suspension:estolate 125 mg/5 mL, 250 mg/5 mL, EES 200 mg/5 mL, 400 mg/5 mL. Estolate drops: 100 mg/mL. EES drops: 100 mg/2.5 mL. Available in combination with sulfisoxazole (Pediazole), dosed on erythromycin content.
INDICATIONS (MECHANISM OF ACTION) AND DOSING pneumoniae. May also be used to promote gastrointestinal motility and improve feeding intolerance in preterm infants. Neonates: Postnatal age 7 days: 20 mg/kg/24 hr divided q 12 hr PO; >7 days <1,200 g: 20 mg/kg/24 hr divided q 12 hr PO; <1,200 g: 30 mg/kg/24 hr divided q 8 hr PO (give as 5 mg/kg/dose q 6 hr to improve feeding intolerance). Children: Usual max dose 2 g/24 hr. Base: 3050 mg/kg/24 hr divided q 68 hr PO. Estolate: 3050 mg/kg/24 hr divided q 812 hr PO. Stearate: 2040 mg/kg/24 hr divided q 6 hr PO. Lactobionate: 2040 mg/kg/24 hr divided q 68 hr IV. Gluceptate: 2050 mg/kg/24 hr divided q 6 hr IV. usual max dose 4 g/24 hr IV. Adults: Base: 333 mg PO q 8 hr; estolate/stearate/base: 250500 mg q 6 hr PO.
COMMENTS Many different salts with questionable tempering of gastrointestinal adverse events. Rare cardiac toxicity with IV use. Dose of salts differ. Topical formulation for treatment of acne. Drug interactions: Antagonizes hepatic CYP450 3A4 activity: astemizole, carbamazepine, terfenadine, cyclosporine, theophylline, digoxin, tacrolimus, carbamazepine.
DRUG (TRADE NAMES, FORMULATIONS) Gentamicin Garamycin. Injection. Ophthalmic solution, ointment, topical cream.
INDICATIONS (MECHANISM OF ACTION) AND DOSING Aminoglycoside antibiotic active against gram-negative bacilli, especially E. coli, Klebsiella, Proteus, Enterobacter, Serratia, and Pseudomonas. Neonates: Postnatal age 7 days 1,2002,000 g: 2.5 mg/kg q 1218 hr IV or IM; <2,000 g: 2.5 mg/kg q 12 hr IV or IM;postnatal age <7 days 1,2002,000 g: 2.5 mg/kg q 812 hr IV or IM; <2,000 g: 2.5 mg/kg q 8 hr IV or IM. Children: 2.5 mg/kg/24 hr divided q 812 hr IV or IM. Alternatively may administer 57.5 mg/kg/24 hr IV once daily. Intrathecal: Preservative-free preparation for intraventricular or intrathecal use:neonate: 1 mg/24 hr; children: 12 mg/24 hr IT;adults: 48 mg/24 hr. Adults: 36 mg/kg/24 hr divided q 8 hr IV or IM.
COMMENTS Cautions: Anaerobes, S. pneumoniae, other Streptococcus are resistant. May cause ototoxicity and nephrotoxicity. Monitor renal function. Drug eliminated renally. Administered IV over 3060 min. Drug interactions: May potentiate other ototoxic and nephrotoxic drugs. Target serum concentrations: Peak 6 12 mg/L;trough >2 mg/L with intermittent daily dose regimens only.
Imipenem-cilastatin Primaxin. Injection.
Carbapenem antibiotic active against broadspectrum gram-
Cautions: -Lactam safety profile (rash, eosinophilia), nausea, seizures. Cilastatin
INDICATIONS (MECHANISM OF ACTION) AND DOSING positive cocci and gram-negative bacilli including P. aeruginosa and anerobes. No activity against Stenotrophomonas maltophilia. Neonates: Postnatal age 7 days <1,200 g: 20 mg/kg q 1824 hr IV or IM; >1,200 g: 40 mg/kg divided q 12 hr IV or IM;postnatal age >7 days 1,2002,000 g: 40 mg/kg q 12 hr IV or IM; >2,000 g: 60 mg/kg q 8 hr IV or IM. Children: 60100 mg/kg/24 hr divided q 68 hr IV or IM. Adults: 24 g/24 hr divided q 68 hr IV or IM (max dose: 4 g/24 hr).
COMMENTS possesses no antibacterial activity; reduces renal imipenem metabolism. Primarily renally eliminated. Drug interaction: Possibly ganciclovir.
Linezolid Zyvox. Tablet: 400, 600 mg. Oral suspension: 100 mg/5 mL. Injection: 100 mg/5 mL.
Oxazolidinone antibiotic active against gram-positive cocci (especially drugresistant organisms), including Staphylococcus, Streptococcus, Enterococcus faecium, and E. fecalis. Interferes with protein synthesis by binding to 50S ribosome subunit.
Adverse events: Myelosuppression, pseudomembranous colitis, nausea, diarrhea, headache. Drug interaction: Probenecid.
INDICATIONS (MECHANISM OF ACTION) AND DOSING Children: 10 mg/kg q 12 hr IV or PO. Adults: Pneumonia: 600 mg q 12 hr IV or PO;skin infections: 400 mg q 12 hr IV or PO.
COMMENTS
Loracarbef Lorabid. Capsule: 200 mg. Suspension: 100 mg/5 mL, 200 mg/5 mL.
Carbacephem very closely related to cefaclor (2nd generation cephalosporin) active against S. aureus, Streptococcus, H. influenzae, M. catarrhalis, E. coli, Klebsiella, and Proteus. Children: 30 mg/kg/24 hr divided q 12 hr PO (max dose: 2 g). Adults: 200400 mg q 12 hr PO (max dose: 800 mg/24 hr).
Meropenem Merrem. Injection.
Carbapenem antibiotic active against broadspectrum grampositive cocci and gram-negative bacilli including P. aeruginosa and anerobes. No activity against Stenotrophomonas maltophilia. Children: 60 mg/kg/24 hr divided q 8 hr IV meningitis: 120
Cautions: -Lactam safety profile; appears to possess less CNS excitation than imipenem. 80% renal elimination. Drug interaction: Probenecid.
INDICATIONS (MECHANISM OF ACTION) AND DOSING mg/kg/24 hr [max: 6 g/24 hr] q 8 hr IV. Adults: 1.53 g q 8 hr IV.
COMMENTS
Metronidazole Flagyl, Metro-IV, generic. Topical gel, vaginal gel. Injection. Tablet: 250,500 mg.
Highly effective in the treatment of infections due to anaerobes. Neonates: <1,200 g: 7.5 mg/kg 48 hr PO or IV;postnatal age 7 days 1,2002,000 g: 7.5 mg/kg/24 hr q 24 hr PO or IV; 2,000 g: 15 mg/kg/24 hr divided q 12 hr PO or IV; postnatal age <7 days 1,2002,000 g: 15 mg/kg/24 hr divided q 12 hr PO or IV; >2,000 g: 30 mg/kg/24 hr divided q 12 hr PO or IV. Children: 30 mg/kg/24 hr divided q 68 hr PO or IV. Adults: 30 mg/kg/24 hr divided q 6 hr PO or IV (max dose: 4 g/24 hr).
Cautions: Dizziness, seizures, metallic taste, nausea, disulfiram-like reaction with alcohol. Administer IV slow over 3060 min. Adjust dose with hepatic impairment. Drug interactions: Carbamazepine, rifampin, phenobarbital may enhance metabolism; may increase levels of warfarin, phenytoin, lithium.
Mezlocillin sodium Mezlin. Infection.
Extended-spectrum penicillin active against E. coli, Enterobacter, Serratia, and Bacteroides; limited antipseudomonal activity. Neonates: Postnatal age
Cautions: -Lactam safety profile (rash, eosinophilia); painful given intramuscularly; each gram contains 1.8 mEq sodium. Interferes with platelet aggregation with high doses; increases noted in
INDICATIONS (MECHANISM OF ACTION) AND DOSING 7 days: 150 mg/kg/24 hr divided q 12 hr IV; >7 days: 225 mg/kg divided q 8 hr IV. Children: 200300 mg/kg/24 hr divided q 46 hr IV;cystic fibrosis 300450 mg/kg/24 hr IV. Adults: 24 g/dose q 4 6 hr IV (max dose: 12 g/24 hr).
COMMENTS liver function test results. Renally eliminated. Inactivated by lactamase enzyme. Drug interaction: Probenecid.
Mupirocin Bactroban. Ointment.
Topical antibiotic active against Staphylococcus and Streptococcus. Topical application: Nasal (eliminate nasal carriage) and to the skin 24 times per day.
Caution: Minimal systemic absorption as drug metabolized within the skin.
Nafcillin sodium Nafcil, Unipen. Injection. Capsule: 250 mg. Tablet: 500 mg.
Penicillinase-resistant penicillin active against S. aureus and other gram-positive cocci except Enterococcus and coagulase-negative staphylococci. Neonates: Postnatal age 7 days 1,2002,000 g: 50 mg/kg/24 hr divided q 12 hr IV or IM; >2,000 g: 75 mg/kg/24 hr divided q 8 hr IV or IM;postnatal age >7 days 1,2002,000 g: 75 mg/kg/q 8 hr; >2,000 g: 100 mg/kg divided q 6
Cautions: -Lactam safety profile (rash, eosinophilia), phlebitis; painful given intramuscularly; oral absorption highly variable and erratic (not recommended). Adverse effect: Neutropenia.
INDICATIONS (MECHANISM OF ACTION) AND DOSING 8 hr IV (meningitis: 200 mg/kg/24 hr divided q 6 hr IV). Children: 100200 mg/kg/24 hr divided q 46 hr IV. Adults: 412 g/24 hr divided q 46 hr IV (max dose: 12 g/24 hr).
COMMENTS
Nalidixic acid NegGram. Tablet: 250,500,1,000 mg. Suspension: 250 mg/5 mL.
1st generation quinolone effective for short-term treatment of lower urinary tract infections caused by E. coli, Enterobacter, Klebsiella, and Proteus. Children: 5055 mg/kg/24 hr divided q 6 hr PO;suppressive therapy 2533 mg/kg/24 hr divided q 68 hr PO. Adults: 1 g q 6 hr PO;suppressive therapy: 500 mg q 6 hr PO.
Cautions: Vertigo, dizziness, rash. Not for use in systemic infections. Drug interactions: Liquid antacids.
Neomycin sulfate Mycifradin, generic. Tablet: 500 mg. Topical cream, ointment. Solution: 125 mg/5 mL.
Aminoglycoside antibiotic used for topical application or orally before surgery to decrease gastrointestinal flora (nonabsorbable) and hyperammonemia. Infants: 50 mg/kg/24 hr divided q 6 hr PO.
Cautions: In patients with renal dysfunction because small amount absorbed may accumulate. Adverse events: Primarily related to topical application, abdominal cramps, diarrhea, rash. Aminoglycoside
INDICATIONS (MECHANISM OF ACTION) AND DOSING Children: 50100 mg/kg/24 hr divided q 68 hr PO. Adults: 5002,000 mg/dose q 68 hr PO.
COMMENTS ototoxicity and nephrotoxicity if absorbed.
Nitrofurantoin Furadantin, Furan, Macrodantin. Capsule: 50,100 mg. Extended-release capsule: 100 mg. Macrocrystal: 50,100 mg. Suspension: 25 mg/5 mL.
Effective in the treatment of lower urinary tract infections caused by gram-positive and gram-negative pathogens. Children: 57 mg/kg/24 hr divided q 6 hr PO (max dose: 400 mg/24 hr); suppressive therapy 12.5 mg/kg/24 hr divided q 1224 hr PO (max dose: 100 mg/24 hr). Adults: 50100 mg/24 hr divided q 6 hr PO.
Cautions: Vertigo, dizziness, rash, jaundice, interstitial pneumonitis. Do not use with moderate to severe renal dysfunction. Drug interactions: Liquid antacids.
Ofloxacin Ocuflox 0.3% ophthalmic solution: 1,5,10 mL. Floxin 0.3% otic solution: 5,10 mL.
Quinolone antibiotic for treatment of conjunctivitis or corneal ulcers (ophthalmic solution); and otitis externa and chronic suppurative otitis media (otic solution) caused by susceptible grampositive, gramnegative, anaerobic bacteria, or Chlamydia trachomatis. Child >112 yr:
Adverse events: Burning, stinging, eye redness (ophthalmic solution), dizziness with otic solution if not warmed.
INDICATIONS (MECHANISM OF ACTION) AND DOSING Conjunctivitis: 12 drops in affected eye(s) q 24 hr for 2 days, then 12 drops qid for 5 days. Corneal ulcers: 12 drops q 30 min while awake and at 4 hours at night for 2 days, then 12 drops hourly for 5 days while awake, then 12 drops q 6 hr for 2 days. Otitis externa (otic solution):5 drops into affected ear bid for 10 days. Chronic suppurative otitis media: treat for 14 days. Child >12 yr and adults: Ophthalmic solution doses same as for younger children. Otitis externa (otic solution): Use 10 drops bid for 10 or 14 days as for younger children.
COMMENTS
Oxacillin sodium Prostaphlin. Injection. Capsule: 250,500 mg. Suspension: 250 mg/5 mL.
Penicillinase-resistant penicillin active against S. aureus and other gram-positive cocci except Enterococcus and coagulase-negative staphylococci. Neonates: Postnatal age
Cautions: -Lactam safety profile (rash, eosinophilia). Moderate oral bioavailability (3565%). Primarily renally eliminated. Drug interaction:
INDICATIONS (MECHANISM OF ACTION) AND DOSING 7 days 1,2002,000 g: 50 mg/kg/24 hr divided q 12 hr IV; >2,000 g: 75 mg/kg/24 hr IV divided q 8 hr IV;postnatal age >7 days <1,200 g: 50 mg/kg/24 hr IV divided q 12 hr IV; 1,200 2,000 g: 75 mg/kg/24 hr divided q 8 hr IV; >2,000 g: 100 mg/kg/24 hr IV divided q 6 hr IV. Infants: 100200 mg/kg/24 hr divided q 46 hr IV. Children: PO 50100 mg/kg/24 hr divided q 46 hr IV. Adults: 212 g/24 hr divided q 46 hr IV (max dose: 12 g/24 hr).
COMMENTS Probenecid. Adverse effect: Neutropenia.
Penicillin G Injection. Tablets.
Penicillin active against most grampositive cocci; S. pneumoniae (resistance is increasing), group A streptococcus, and some gram-negative bacteria (e.g., N. gonorrhoeae, N. meningitidis). Neonates: Postnatal age 7 days 1,2002,000 g: 50,000 units/kg/24 hr divided q 12 hr IV or IM (meningitis:
Cautions: -Lactam safety profile (rash, eosinophilia), allergy, seizures with excessive doses particularly in patients with marked renal disease. Substantial pathogen resistance. Primarily renally eliminated. Drug interaction: Probenecid.
INDICATIONS (MECHANISM OF ACTION) AND DOSING 100,000 units/kg/24 hr divided q 12 hr IV or IM); >2,000 g: 75,000 units/kg/24 hr divided q 8 hr IV or IM (meningitis: 150,000 units/kg/24 hr divided q 8 hr IV or IM); postnatal age >7 days 1,200 g: 50,000 units/kg/24 hr divided q 12 hr IV (meningitis: 100,000 units/kg/24 hr divided q 12 hr IV);1,2002,000 g: 75,000 units/kg/24 hr q 8 hr IV (meningitis: 225,000 units/kg/24 hr divided q 8 hr IV); >2,000 g: 100,000 units/kg/24 hr divided q 6 hr IV (meningitis: 200,000 units/kg/24 hr divided q 6 hr IV). Children: 100,000 250,000 units/kg/24 hr divided q 46 hr IV or IM (max: 400,000 units/kg/24 hr). Adults: 224 million units/24 hr divided q 4 6 hr IV or IM
COMMENTS
Penicillin G, benzathine Bicillin. Injection.
Long-acting repository form of penicillin effective in the treatment of infections responsive to persistent, low penicillin concentrations (14
Cautions: -Lactam safety profile (rash, eosinophilia), allergy. Administer by IM injection only. Substantial pathogen resistance. Primarily renally eliminated.
INDICATIONS (MECHANISM OF ACTION) AND DOSING wk), e.g., group A streptococcus pharyngitis, rheumatic fever prophylaxis. Neonates >1,200 g: 50,000 units/kg IM once. Children: 300,0001.2 million units/kg q 34 wk IM (max: 1.22.4 million units/dose). Adults: 1.2 million units IM q 34 wk.
COMMENTS Drug interaction: Probenecid.
Penicillin G, procaine Crysticillin. Injection.
Repository form of penicillin providing low penicillin concentrations for 12 hr. Neonates >1,200 g: 50,000 units/kg/24 hr IM. Children: 25,000 50,000 units/kg/24 hr IM for 10 days (max: 4.8 million units/dose). Gonorrhea: 100,000 units/kg (max: 4.8 million units/24 hr) IM once with probenecid 25 mg/kg (max dose: 1 g) Adults: 0.64.8 million units q 1224 hr IM.
Cautions: -Lactam safety profile (rash, eosinophilia) allergy. Administer by IM injection only. Substantial pathogen resistance. Primarily renally eliminated. Drug interaction: Probenecid.
Penicillin V Pen VK, V-Cillin K.
Preferred oral dosing form of penicillin, active against most
Cautions: -Lactam safety profile (rash, eosinophilia), allergy,
DRUG (TRADE NAMES, FORMULATIONS) Tablet: 125,250,500 mg. Suspension: 125 mg/5 mL, 250 mg/5 mL.
INDICATIONS (MECHANISM OF ACTION) AND DOSING gram-positive cocci; S. pneumoniae (resistance is increasing), other Streptococcus, and some gram-negative bacteria (e.g., N. gonorrhoeae, N. meningitidis). Children: 2550 mg/kg/24 hr divided q 48 hr PO. Adults: 125500 mg q 68 hr PO (max dose: 3 g/24 hr).
COMMENTS seizures with excessive doses particularly in patients with renal disease. Substantial pathogen resistance. Primarily renally eliminated. Inactivated by penicillinase. Drug interaction:Probenecid.
Piperacillin Pipracil. Injection.
Extended-spectrum penicillin active against E. coli, Enterobacter, Serratia, P. aeruginosa, and Bacteroides. Neonates: Postnatal age 7 days 150 mg/kg/24 hr divided q 812 hr IV; >7 days; 200 mg/kg divided q 68 hr IV. Children: 200300 mg/kg/24 hr divided q 46 hr IV;cystic fibrosis: 350500 mg/kg/24 hr IV. Adults: 24 g/dose q 4 6 hr (max dose: 24 g/24 hr) IV.
Cautions: -Lactam safety profile (rash, eosinophilia); painful given intramuscularly; each gram contains 1.9 mEq sodium. Interferes with platelet aggregation/serum sicknesslike reaction with high doses; increases in liver function tests. Renally eliminated. Inactivated by penicillinase. Drug interaction: Probenecid.
Piperacillin-tazobactam Zosyn. Injection.
Extended-spectrum penicillin (piperacillin) combined with a -
Cautions: -Lactam safety profile (rash, eosinophilia); painful given intramuscularly;
INDICATIONS (MECHANISM OF ACTION) AND DOSING lactamase inhibitor (tazobactam) active against S. aureus, H. influenzae, E. coli, Enterobacter, Serratia, Acinetobacter, P. aeruginosa, and Bacteroides. Children: 300400 mg/kg/24 hr divided q 68 hr IV or IM. Adults: 3.375 g q 68 hr IV or IM.
COMMENTS each gram contains 1.9 mEq sodium. Interferes with platelet aggregation, serum sincknesslike reaction with high doses, increases in liver function test results. Renally eliminated. Drug interaction: Probenecid.
Quinupristin/dalfopristin Synercid. IV injection: powder for reconstitution, 10 mL contains 150 mg quinupristin, 350 mg dalfopristin.
Streptogramin antibiotic (quinupristin) active against vancomycinresistant E. faecium (VRE) and methicillin-resistant S. aureus. Not active against E. faecalis. Children and adults: VRE:7.5 mg/kg q 8 hr IV for VRE;skin infections: 7.5 mg/kg q 12 hr IV.
Adverse events: Pain, edema, or phlebitis at injection site, nausea, diarrhea. Drug interactions: Synercid is a potent inhibitor of CYP3A4.
Sulfadiazine Tablet: 500 mg.
Sulfonamide antibiotic primarily indicated for the treatment of lower urinary tract infections due to E. coli, P. mirabilis, and Klebsiella. Toxoplasmosis: Neonates: 100 mg/kg/24 hr divided q
Cautions: Rash, StevensJohnson syndrome, nausea, leukopenia, crystalluria. Renal and hepatic elimination; avoid use with renal disease. Half-life 10 hr. Drug interactions: Protein displacement with warfarin, phenytoin, methotrexate.
INDICATIONS (MECHANISM OF ACTION) AND DOSING 12 hr PO with pyrimethamine 1 mg/kg/24 hr PO (with folinic acid). Children: 120200 mg/kg/24 hr divided q 6 hr PO with pyrimethamine 2 mg/kg/24 hr divided q 12 hr PO 3 days then 1 mg/kg/24 hr (max dose: 25 mg/24 hr) with folinic acid. Rheumatic fever prophylaxis: 30 kg: 500 mg/24 hr q 24 hr PO; >30 kg: 1 g/24 hr q 24 hr PO.
COMMENTS
Sulfamethoxazole Gantanol. Tablet: 500 mg. Suspension: 500 mg/5 mL.
Sulfonamide antibiotic used for the treatment of otitis media, chronic bronchitis, and lower urinary tract infections due to susceptible bacteria. Children: 5060 mg/kg/24 hr divided q 12 hr PO. Adults: 1 g/dose q 12 hr PO (max dose: 3 g/24 hr).
Cautions: Rash, StevensJohnson syndrome, nausea, leukopenia, crystalluria. Renal and hepatic elimination; avoid use with renal disease. Half-life 12 hr. Initial dose often a loading dose (doubled). Drug interactions: Protein displacement with warfarin, phenytoin, methotrexate.
Sulfisoxazole Gantrisin. Tablet: 500 mg. Suspension: 500 mg/5 mL.
Sulfonamide antibiotic used for the treatment of otitis media, chronic bronchitis, and lower urinary tract
Cautions: Rash, StevensJohnson syndrome, nausea, leukopenia, crystalluria. Renal and hepatic elimination; avoid use with renal
DRUG (TRADE NAMES, FORMULATIONS) Ophthalmic solution, ointment.
INDICATIONS (MECHANISM OF ACTION) AND DOSING infections due to susceptible bacteria. Children: 120150 mg/kg/24 hr divided q 46 hr PO (max dose: 6 g/24 hr). Adults: 48 g/24 hr divided q 46 hr PO.
COMMENTS disease. Half-life 712 hr. Initial dose often a loading dose (doubled). Drug interactions: Protein displacement with warfarin, phenytoin, methotrexate.
Ticarcillin Ticar. Injection.
Extended-spectrum penicillin active against E. coli, Enterobacter, Serratia, P. aeruginosa, and Bacteroides. Neonates: Postnatal age 7 days <2,000 g: 150 mg/kg/24 hr divided q 812 hr IV; >7 days: <2,000 g: 225 mg/kg/24 hr divided q 8 hr IV; >7 days <1,200 g: 150 mg/kg/24 hr divided q 12 hr IV; 1,2002,000 g: 225 mg/kg/24 hr divided q 8 hr IV; >2,000 g: 300 mg/kg/24 hr divided q 68 hr IV. Children: 200400 mg/kg/24 hr divided q 46 hr IV;cystic fibrosis: 400600 mg/kg/24 hr IV. Adults: 24 g/dose q 4 6 hr IV (max dose: 24 g/24 hr).
Cautions: -Lactam safety profile (rash, eosinophilia); painful given intramuscularly; each gram contains 56 mEq sodium. Interferes with platelet aggregation; increases in liver function tests. Renally eliminated. Inactivated by penicillinase. Drug interaction: Probenecid.
Ticarcillin-clavulanate
Extended-spectrum penicillin (ticarcillin)
Cautions: -Lactam safety profile (rash,
DRUG (TRADE NAMES, FORMULATIONS) Timentin. Injection.
INDICATIONS (MECHANISM OF ACTION) AND DOSING combined with a lactamase inhibitor (clavulanate) active against S. aureus, H. influenzae, Enterobacter, E. coli, Serratia, P. aeruginosa, Acinetobacter, and Bacteroides. Children: 280400 mg/kg/24 hr q 48 hr IV or IM. Adults: 3.1 g q 48 hr IV or IM (max dose: 1824 g/24 hr).
COMMENTS eosinophilia); painful given intramuscularly; each gram contains 56 mEq sodium. Interferes with platelet aggregation; increases in liver function tests. Renally eliminated. Drug interaction: Probenecid.
Tobramycin Nebcin, Tobrex. Injection. Ophthalmic solution, ointment.
Aminoglycoside antibiotic active against gram-negative bacilli, especially E. coli, Klebsiella, Enterobacter, Serratia, Proteus, and Pseudomonas. Neonates: Postnatal age 7 days, 1,2002,000 g: 2.5 mg/kg q 1218 hr IV or IM; >2,000 g: 2.5 mg/kg q 12 hr IV or IM;postnatal age >7 days, 1,2002,000 g: 2.5 mg/kg q 812 hr IV or IM; >2,000 g: 2.5 mg/kg q 8 hr IV or IM. Children: 2.5 mg/kg/24 hr divided q 812 hr IV or IM. Alternatively may administer 57.5 mg/kg/24 hr IV.
Cautions: S. pneumoniae, other Streptococcus, and anaerobes are resistant. May cause ototoxicity and nephrotoxicity. Monitor renal function. Drug eliminated renally. Administered IV over 3060 min. Drug interactions: May potentiate other ototoxic and nephrotoxic drugs. Target serum concentrations: Peak 6 12 mg/L;trough <2 mg/L.
INDICATIONS (MECHANISM OF ACTION) AND DOSING Preservative-free preparation for intraventricular or intrathecal use:neonate: 1 mg/24 hr; children: 12 mg/24 hr; adults: 48 mg/24 hr. Adults: 36 mg/kg/24 hr divided q 8 hr IV or IM.
COMMENTS
Trimethoprim Proloprim, Trimpex. Tablet: 100,200 mg
Folic acid antagonist effective in the prophylaxis and treatment of E. coli, Klebsiella, Proteus mirabilis, and Enterobacter urinary tract infections; P. carinii pneumonia. Children: For urinary tract infection: 46 mg/kg/24 hr divided q 12 hr PO. Children >12 yr and adults: 100200 mg q 12 hr PO. P. carinii pneumonia (with dapsone):1520 mg/kg/24 hr divided q 6 hr for 21 days PO.
Cautions: Megaloblastic anemia, bone marrow suppression, nausea, epigastric distress, rash. Durg interactions: Possible interactions with phenytoin, cyclosporine, rifampin, warfarin.
Vancomycin Vancocin, Luphocin. Injection. Capsule: 125 mg, 250 mg. Suspension.
Glycopeptide antibiotic active against most grampositive pathogens including Staphylococcus (including methicillinresistant S. aureus
Cautions: Ototoxicity and nephrotoxicity particularly when coadministered with other ototoxic and nephrotoxic drugs. Infuse IV over 45 60 min. Flushing (redman syndrome)
INDICATIONS (MECHANISM OF ACTION) AND DOSING and coagulasenegative staphylococci), S. pneumoniae including penicillin-resistant strains, Enterococcus (resistance is increasing), and Clostridium difficileassociated colitis. Neonates: Postnatal age 7 days, <1,200 g: 15 mg/kg/24 hr divided q 24 hr IV; 1.2002,000 g: 15 mg/kg/24 hr divided q 1218 hr IV; >2,000 g: 30 mg/kg/24 hr divided q 12 hr IV;postnatal age >7 days, <1,200 g: 15 mg/kg/24 hr divided q 24 hr IV; 1,2002,000 g: 15 mg/kg/24 hr divided q 812 hr IV; >2,000 g: 45 mg/kg/24 hr divided q 8 hr IV. Children: 4560 mg/kg/24 hr divided q 812 hr IV; Clostridium difficileassociated colitis; 40 50 mg/kg/24 hr divided q 68 hr PO. Adults: 0.51 g IV q 12 hr IV.
COMMENTS associated with rapid IV infusions, fever, chills, phlebitis (central line is preferred). Renally eliminated. Target serum concentrations: Peak (1 hr after 1 hr infusion) 3040 mg/L;trough 510 mg/L.
Penicillins remain the drugs of choice for many common pediatric infections caused by group A and group B streptococcus, Treponema pallidum (syphilis), Listeria monocytogenes, and Neisseria meningitidis. The semisynthetic penicillins (nafcillin, cloxacillin, dicloxacillin) are
useful for management of susceptible staphylococcal infections, although increasing incidence of MRSA has limited the usefulness of these drugs. The aminopenicillins (ampicillin, amoxicillin) were developed to provide broad-spectrum activity against gram-negative organisms, including E. coli and H. influenzae, but the emergence of resistance has limited their utility in many clinical settings. The carboxypenicillins (carbenicillin, ticarcillin) and ureidopenicillins (piperacillin, mezlocillin, azlocillin) also have bactericidal activity against most strains of P. aeruginosa. Resistance to penicillin is mediated by a variety of mechanisms (see Table 179-1 ). The production of -lactamase is a common mechanism exhibited by many organisms that may be overcome, with variable success, by including a -lactamase inhibitor with the penicillin. These combination products (ampicillin-sulbactam, amoxicillin-clavulanate, piperacillin-tazobactam) are very useful for management of resistant isolates if the resistance is -lactamase mediated. Notably, S. aureus and S. pneumoniae mediate -lactam resistance through mechanisms other than -lactamase production, rendering these combination agents of little value for the management of these infections. Adverse reactions to penicillins are noted in Table 179-4 . TABLE 179-4 -- Adverse Reactions to Penicillins[*] FREQUENCY TYPE OF REACTION (%) ALLERGIC IgE antibody Anaphylaxis Early urticaria (<72 h) Cytotoxic antibody Hemolytic anemia Antigen-antibody complex disease Serum sickness Delayed hypersensitivity Contact dermatitis IDIOPATHIC Skin rash Fever Late-onset urticaria GASTROINTESTINAL Diarrhea 25 25 Ampicillin 48 Ampicillin 48 Ampicillin Rare Penicillin G Rare Penicillin G 0.0040.4 Penicillin G
OCCURS MOST FREQUENTLY WITH[*]
TYPE OF REACTION Enterocolitis HEMATOLOGIC Hemolytic anemia Neutropenia Platelet dysfunction HEPATIC Elevated serum aspartate transaminase level ELECTROLYTE DISTURBANCE Sodium overload Hypokalemia Hyperkalemiaacute NEUROLOGIC Seizures Bizarre sensations RENAL Interstitial nephritis
FREQUENCY (%) <1 Rare 14 3 14
OCCURS MOST FREQUENTLY WITH[*] Ampicillin Penicillin G Penicillin G, nafcillin, oxacillin, piperacillin Carbenicillin, ticarcillin Oxacillin, nafcillin, carbenicillin
Variable Variable Rare Rare
Ticarcillin Ticarcillin Penicillin G Penicillin G Procaine penicillin
12
Methicillin
Hemorrhagic cystitis Rare Methicillin From Mandell GL, Bennett JE, Dolin R (editors):Principles and Practice of Infectious Diseases, 6th ed, Vol 1. Philadelphia, Elsevier, 2005, p 286.
*
All the reactions can occur with any of the penicillins.
Cephalosporins.
Cephalosporins differ structurally from penicillins by having the -lactam ring as a 6 member ring, compared to the 5 member ring structure of the penicillins. These agents are widely used in pediatric practice, both in oral and parenteral formulations ( Table 179-5 ). The 1st generation cephalosporins (cefazolin, a parenteral formulation, and cephalexin, an oral equivalent) are commonly used for management of skin and soft tissue infections caused by susceptible strains of S. aureus and group A streptococcus. The 2nd generation cephalosporins (cefuroxime, cefoxitin) have better activity against gram-negative infections than do 1st generation cephalosporins and are used to treat respiratory tract infections, urinary tract infections, and softtissue infections. A variety of orally administered 2nd generation agents (cefaclor, cefprozil, loracarbef, cefpodoxime) are commonly used in the outpatient management of sinopulmonary infections. The 3rd generation cephalosporins (cefotaxime, ceftriaxone, and ceftazidime) are
used for serious pediatric infections, including meningitis and sepsis. Ceftazidime is highly active against most strains of P. aeruginosa, making this a useful agent for febrile, neutropenic oncology patients. Another class of4th generation cephalosporins (cefepime) is indicated for treatment of pediatric meningitis, has activity against P. aeruginosa, and retains good activity against methicillin-susceptible staphylococcal infections.
TABLE 179-5 -- Classification of Parenteral and Oral Cephalosporins 1ST 2ND 3RD 4TH CEPHALOSPOR GENERATI GENERATI CEPHAMYCI GENERATI GENERATI INS ON ON NS ON ON Parenteral Cefazolin (Ancef, Kefzol) Cephalothin (Keflin, Seffin) Cephapirin (Cefadyl) Cephradine (Velosef) Cefamandole Cefmetazole (Mandol) (Zefazone) Cefonicid (Monocid) Cefuroxime (Kefurox, Zinacef) Cefotetan (Cefotan) Cefoxitin (Mefoxin) Cefoperazole Cefepime (Cefobid) (Maxipime) Cefotaxime (Claforan) Ceftazidime (Fortaz) Ceftizoxime (Cefizox) Ceftriaxone (Rocephin) Oral Cefadroxil (Duricef, Ultracef) Cephalexin (Keflex, Biocef, Keftab) Cephradine (Velosef) Cefaclor (Ceclor) Cefprozil (Cefzil) Cefdinir (Omnicef) Cefditoren (Spectracef) Cefpirome
Cefuroximeaxetil (Ceftin) Loracarbef (Lorabid)
Cefixime (Suprax) Cefpodoxime (Vantin)
Ceftibuten (Cedax) From Mandell GL, Bennett JE, Dolin R (editors): Principles and Practice of Infectious Diseases, 6th ed, Vol 1. Philadelphia, Elsevier, 2005, p 297.
Adverse reactions to cephalosporins are noted in Table 179-6 .
TABLE 179-6 -- Potential Adverse Effects of Cephalosporins TYPE SPECIFIC FREQUENCY Hypersensitivity Rash Urticaria Serum sickness Anaphylaxis Gastrointestinal Diarrhea Nausea, vomiting Biliary sludge Hematologic Eosinophilia Neutropenia Thrombocytopenia Hypoprothrombinemia Impaired platelet aggregation Hemolytic anemia Renal Interstitial nephritis Central nervous system Seizures False-positive laboratory Coombs positive Glucosuria Serum creatinine Other Drug fever Disulfiram-like reaction[] Superinfection Rare Rare Rare 3% Rare Rare <1% <1% 110% <1% <13% <1% <1% <1% 119% 16% 2046%[*] 13% <1% <1% 0.01%
Transient transaminase elevation 17%
TYPE
SPECIFIC
FREQUENCY
Phlebitis Rare From Mandell GL, Bennett JE, Dolin R (editors):Principles and Practice of Infectious Diseases, 6th ed, Vol 1. Philadelphia, Elsevier, 2005, p 303.
*
Ceftriaxone. Cephalosporins with thiomethyl tetrazole ring (MTT) side chain.
Carbapenems.
The carbapenems include imipenem, which is a combination of thienamycin and cilastatin, and the newer agents, meropenem and ertapenem. The basic structure of these agents is similar to that of -lactam antibiotics, with a similar mechanism of action. The carbapenems provide the broadest spectrum of antibacterial activity of any licensed class of antibiotics, and are active against gram-positive, gram-negative, and anaerobic organisms. Meropenem is licensed for treatment of pediatric meningitis. MRSA and Enterococcus faecium are not susceptible to carbapenems. Carbapenems also tend to be poorly active against Stenotrophomonas maltophilia, rendering their use for cystic fibrosis patients colonized with this organism problematic. The 1st carbapenem approved for clinical use was imipenem-cilastatin, which has a propensity to cause seizures in children, particularly in the setting of meningitis, and therefore meropenem is more suitable for pediatric use.
Glycopeptides.
Glycopeptide antibiotics include vancomycin and teicoplanin, the less commonly available analog. These agents are bacteriocidal and act via inhibition of cell wall biosynthesis. The antimicrobial activity of the glycopeptides is limited to gram-positive organisms, including S. aureus, coagulase-negative staphylococci, pneumococcus, Enterococcus, Bacillus, and Corynebacterium. Vancomycin is frequently employed in pediatric practice and is of particular value for serious infections, including meningitis, caused by MRSA and penicillin- and cephalosporin-resistant S. pneumoniae. Vancomycin is also commonly used for infections in the setting of fever and neutropenia, in combination with other antibiotics, in oncology patients (see Chapter 177 ), and infections associated with indwelling medical devices (see Chapter 178 ). Oral formulations of vancomycin are occasionally used to treat pseudomembranous colitis due to Clostridium difficile infections; intrathecal therapy may also be used for selected CNS infections. Vancomycin must be administered with care due to its propensity to produce red-man syndrome, which is a reversible adverse effect that is rare in young children and can typically be readily managed by slowing the rate of infusion of the drug.
Aminoglycosides.
Aminoglycoside antibiotics include streptomycin, kanamycin, gentamicin, tobramycin, netilmicin, and amikacin. The most commonly used aminoglycosides in pediatric practice are gentamicin and tobramycin. They exert their mechanism of action via inhibition of bacterial protein synthesis. Although they are most commonly used to treat gram-negative infections, the aminoglycosides are broad-spectrum agents and have activity against S. aureus and provide
synergistic activity against group B streptococcus, L. monocytogenes, viridans streptococci, corynebacteria JK, Pseudomonas, Staphylococcus epidermidis, and Enterococcus when coadministered with a -lactam agent. Aminoglycoside use has decreased with the development of newer alternatives, but they still play a key role in pediatric practice in the management of neonatal sepsis, urinary tract infections, gram-negative sepsis, and complicated intra-abdominal infections; infections in cystic fibrosis patients (including both parenteral and aerosolized forms of therapy); and in oncology patients with fever and neutropenia. Aminoglycosides, in particular streptomycin, are also important in the management of Francisella tularensis, Mycobacterium tuberculosis, and atypical mycobacterial infections. Toxicities of aminoglycoside therapy include nephrotoxicity and ototoxicity (cochlear and/or vestibular), and serum levels as well as renal function and hearing should be monitored for patients on long-term therapy. Toxicities of aminoglycosides may be reduced by the use of once-daily dosing regimens based on monitoring serum levels. Hypokalemia, volume depletion, hypomagnesemia, and other nephrotoxic drugs may increase the renal toxicity of aminoglycosides. A rare complication of aminoglycosides is neuromuscular blockade, which may occur in the presence of other neuromuscular blocking agents and with infant botulism.
Tetracyclines.
The tetracyclines (tetracycline hydrochloride, doxycycline, and minocycline) are bacteriostatic antibiotics that exhibit their antimicrobial effect by binding to the bacterial 30S ribosomal subunit, inhibiting protein translation. These agents have a broad spectrum of antimicrobial activity against gram-positive and -negative bacteria, rickettsia, and some parasites. The oral bioavailability of these agents facilitates this route of dosing for many infections including Rocky Mountain spotted fever, ehrlichiosis, Lyme disease, and malaria. Tetracyclines must be prescribed judiciously to children <9 yr of age because they can cause staining of teeth, hypoplasia of dental enamel, and abnormal bone growth in this age group. Tigecycline, a semisynthetic derivative of minocycline, was recently licensed in the United States. It is a parenteral agent of a new class of antibiotics (glycylglycines). It has a broader spectrum of activity (bacteriostatic) than traditional tetracyclines, including activity against tetracycline-resistant gram-positive and -negative pathogens, including MRSA and possibly VRE but not Pseudomonas. Complications of tetracyclines include eosinophilia, leukopenia and thrombocytopenia (tetracycline), pseudotumor cerebri, anorexia, emesis and nausea, candidiasis superinfection, hepatitis, photosensitivity, and a hypersensitivity reaction (urticaria, asthma exacerbation, facial edema, dermatitis) as well as a systemic lupus erythematosuslike syndrome (minocycline).
Sulfonamides.
Trimethoprim and the sulfonamides are bacteriostatic agents that inhibit the bacterial folate synthesis pathway, in the process impairing both nucleic acid and protein synthesis. Sulfonamides interfere with the synthesis of dihydropteroic acid from para-aminobenzoic acid, whereas trimethoprim acts at a site further downstream, interfering with synthesis of tetrahydrofolic acid from dihydrofolic acid. The sulfonamides are available in both parenteral and oral formulations. Although there have historically been a large number of sulfonamide
antibiotics developed for clinical use, relatively few remain available for pediatric practice. The most important agent is the combination of trimethoprim-sulfamethoxazole, which is commonly used for treatment of urinary tract infections and for Pneumocystis carinii infections in immunocompromised patients. Other commonly used sulfonamides include sulfisoxazole, which is used to treat urinary tract infections, and sulfadiazine, which is used to treat toxoplasmosis and as alternative prophylaxis against acute rheumatic fever.
Macrolides.
The macrolide antibiotics most commonly employed in pediatric practice include erythromycin and the newer agents clarithromycin and azithromycin. These agents bind to the 50S subunit of the bacterial ribosome and block elongation of bacterial polypeptides. The spectrum of antibiotic activity includes many gram-positive infections, including S. aureus and group A streptococcus, although resistance to these agents is now fairly widespread, limiting the usefulness of macrolides for skin and soft tissue infections and streptococcal pharyngitis. The newer macrolides, azithromycin and clarithromycin, have demonstrated efficacy for otitis media. All of the members of this class have an important role in the management of pediatric respiratory infections, including atypical pneumonia caused by M. pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila, as well as infections caused by Bordetella pertussis. Telithromycin is a ketolide antibiotic derived from the macrolide erythromycin. It is FDA approved in adults for the treatment of mild to moderate community-acquired pneumonia, acute exacerbations of chronic bronchitis, and acute sinusitis, having good activity against the agents causing these infections (pneumococcus, M. pneumoniae, C. pneumoniae, and L. pneumophila for community-acquired pneumonia; M. catarrhalis and H. influenzae for sinusitis). Drug interactions are common with erythromycin and telithromycin, and less so with clarithromycin. These agents can inhibit the CYP3A4 enzyme system, resulting in increased levels of certain drugs such as astemizole, cisapride, the statins, pimozide, and theophylline. Other agents (itraconazole) may increase macrolide levels, while rifampin, carbamazepine, and phenytoin may decrease macrolide levels. There are few reported adverse drug interactions with azithromycin. Cross-resistance may develop between a macrolide and the subsequent use of clindamycin.
Lincosamides.
The prototype of the lincosamide class of antibiotics is clindamycin, which acts at the ribosomal level to exert its antimicrobial effect. The spectrum of activity includes gram-positive aerobes and anaerobes. Clindamycin has no significant activity against gram-negative organisms. An important role for clindamycin has emerged in the management of MRSA infections. Because of its outstanding penetration into body fluids (exclud ing the CNS) and tissues and bone, clindamycin can be utilized for therapy of serious infections caused by MRSA. Clindamycin is also useful, usually in combination with a -lactam, in the management of invasive group A streptococcus infections, and in the management of many anaerobic infections. There is a form of inducible clindamycin resistance exhibited by some strains of MRSA; therefore, consultation with the clinical microbiology laboratory is necessary before treating a serious
MRSA infection with clindamycin. Pseudomembranous colitis, a complication of clindamycin therapy commonly encountered in adults, is seldom observed in pediatric patients.
Quinolones.
The fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin, gemifloxacin) are newer antimicrobials that inhibit bacterial DNA replication by binding to the topoisomerases of the target pathogen, inhibiting the bacterial enzyme, DNA gyrase, and DNA replication. This class has very broad-spectrum activity against both gram-positive and gram-negative organisms. Some of the fluoroquinolones exhibit activity against penicillin-resistant S. pneumoniae as well as MRSA. These agents uniformly exhibit excellent activity against gram-negative pathogens, including the Enterobacteriaceae, and respiratory tract pathogens such as M. catarrhalis and H. influenzae. Quinolones are also very active against pathogens associated with atypical pneumonia, particularly M. pneumoniae and L. pneumophila. Although these agents are not approved for use in children, there is a reasonable body of evidence that the fluoroquinolones are safe, well tolerated, and effective against a variety of bacterial infections in children. Parenteral quinolones are appropriate for critically ill patients with gram-negative infections. The use of oral quinolones in stable outpatients is also reasonable for treatment of infections that would otherwise require parenteral antibiotics (P. aeruginosa soft tissue infections such as osteochondritis) or selected genitourinary tract infections. However, they should be reserved for situations where no other oral antibiotic alternative is feasible. Where they have been used frequently (typhoid fever) organisms may rapidly develop resistance.
Streptogramins and Oxazolidinones.
The emergence of highly resistant gram-positive organisms, in particular VRE, has necessitated development of new classes of antibiotics to treat these infections. One class of antibiotics that is highly useful for resistant gram-positive infections is the streptogramin class. The currently licensed agent in this category, dalfopristin-quinupristin, is approved in a parenteral formulation for patients >16 yr of age. It is appropriate for treatment of MRSA, coagulasenegative staphylococcus, penicillin-susceptible and penicillin-resistant pneumococcus, and vancomycin-resistant E. faecium but not E. faecalis. Another licensed class of antibiotics for highly resistant gram-positive infections is the oxazolidinone class. The prototype of this group is the linezolid, which is available in both oral and parenteral formulations and is approved for use in pediatric patients. Its mechanism of action is through inhibition of ribosomal protein synthesis. It is indicated for MRSA, VRE, coagulasenegative staphylococci, and penicillin-resistant pneumococci. There is little information on dalfopristin-quinupristin and linezolid in treatment of infections involving the CNS, and neither agent is approved for pediatric meningitis. Linezolid can cause anemia and thrombocytopenia and is a monoamine oxidase inhibitor.
Daptomycin.
Daptomycin is a cyclic lipopeptide with a spectrum of activity that includes virtually all grampositive organisms, including E. faecalis and E. faecium (including VRE) and S. aureus (including MRSA). The structure of daptomycin is a 13 member amino acid peptide linked to a 10 carbon lipophilic tail, which results in a novel mechanism of action of disruption of the bacterial membrane through the formation of transmembrane channels. These channels cause leakage of intracellular ions leading to depolarizing the cellular membrane and inhibition of macromolecular synthesis. A theoretical advantage of daptomycin for serious infections is its bactericidal activity against MRSA and Enterococcus. It is administered IV. Experience in children is limited. Myopathy and elevations in creatine phosphokinase have been described. Daptomycin is inactivated by surfactant and should not be used to treat pneumonia.
Miscellaneous Agents.
Although rarely used today because of safety concerns, chloramphenicol still occasionally plays a role in the management of pediatric infections, particularly those involving the CNS. This agent binds peptidyl transferase, a component of the 50S ribosome, inhibiting bacterial protein synthesis. Metronidazole, which functions by disruption of DNA synthesis, has a unique role as an anti-anaerobic agent as well as possessing antiparasitic and anthelminthic activity. Rifampin, which inhibits bacterial RNA polymerase, has a major role in the management of tuberculosis and is also of value for other bacterial infections in pediatric patients, usually used as a 2nd (synergistic) agent for S. aureus infections or to eliminate nasopharyngeal colonization of H. influenzae type b and N. meningitidis. Email to Colleague Print Version Copyright 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com

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Kliegman: Nelson Textbook of Pediatrics, 18th ed.

Copyright 2007 Saunders, An Imprint of Elsevier

Section 3 Antibiotic Therapy

Chapter 179 Principles of Antibacterial Therapy

AAC(3)-III, -IV, OR-V K, T, G

AGE- AND RISK-SPECIFIC USE OF ANTIBIOTICS IN CHILDREN. Neonates.

DRUG (TRADE NAMES, FORMULATIONS)

COMMENTS concentrations: Peak 25 40 mg/L;trough <10 mg/L.

Amoxicillin-clavulanate Augmentin. Tablet: 250,500,875 mg. Tablet, chewable: 125,200,250,400 mg.

DRUG (TRADE NAMES, FORMULATIONS)

Ampicillin-sulbactam Unasyn. Injection.

Azalide antibiotic with activity against

Note: very long half-life permitting once-daily dosing.

Aztreonam Azactam. Injection.

Cautions: Rash, thrombophlebitis, eosinophilia. Renally eliminated. Drug interaction: Probenecid.

DRUG (TRADE NAMES, FORMULATIONS)

Carbenicillin Geopen Injection. Geocillin oral tablet.

2nd generation cephalosporin active against S. aureus,

Cautions: -Lactam safety profile (rash, eosinophilia) with high

Cefazolin Ancef, Kefzol. Injection.

DRUG (TRADE NAMES, FORMULATIONS)

Cefepime Maxipime. Injection.

Cefixime Suprax. Tablet: 200,400 mg. Suspension: 100 mg/5 mL.

DRUG (TRADE NAMES, FORMULATIONS)

Cefoperazone sodium Cefobid. Injection.

Cefotaxime sodium Claforan. Injection.

DRUG (TRADE NAMES, FORMULATIONS)

Cefotetan disodium Cefotan. Injection.

Cefoxitin sodium Mefoxin. Injection.

DRUG (TRADE NAMES, FORMULATIONS)

DRUG (TRADE NAMES, FORMULATIONS)

Ceftazidime Fortaz, Ceptaz, Tazicer, Tazidime. Injection.

Ceftiaoxime Cefizox. Injection.

DRUG (TRADE NAMES, FORMULATIONS)

Ceftriaxone sodium Rocephin. Injection.

DRUG (TRADE NAMES, FORMULATIONS)

Chloramphenicol Chloromycetin. Injection. Capsule: 250 mg. Ophthalmic, otic solutions.

DRUG (TRADE NAMES, FORMULATIONS) Ointment.

DRUG (TRADE NAMES, FORMULATIONS) 500 mg/5 mL.

COMMENTS probenecid, warfarin, cyclosporine.

DRUG (TRADE NAMES, FORMULATIONS)

Demeclocycline Declomycin. Tablet: 150,300 mg. Capsule: 150 mg.

Imipenem-cilastatin Primaxin. Injection.

Carbapenem antibiotic active against broadspectrum gram-

Cautions: -Lactam safety profile (rash, eosinophilia), nausea, seizures. Cilastatin

DRUG (TRADE NAMES, FORMULATIONS)

DRUG (TRADE NAMES, FORMULATIONS)

Meropenem Merrem. Injection.

DRUG (TRADE NAMES, FORMULATIONS)

Mezlocillin sodium Mezlin. Infection.

DRUG (TRADE NAMES, FORMULATIONS)

Mupirocin Bactroban. Ointment.

Caution: Minimal systemic absorption as drug metabolized within the skin.

DRUG (TRADE NAMES, FORMULATIONS)

DRUG (TRADE NAMES, FORMULATIONS)

COMMENTS ototoxicity and nephrotoxicity if absorbed.

DRUG (TRADE NAMES, FORMULATIONS)

DRUG (TRADE NAMES, FORMULATIONS)

COMMENTS Probenecid. Adverse effect: Neutropenia.

Penicillin G Injection. Tablets.

DRUG (TRADE NAMES, FORMULATIONS)

Penicillin G, benzathine Bicillin. Injection.

DRUG (TRADE NAMES, FORMULATIONS)