Principles of Antibacterial Therapy

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Chapter 173 Principles of Antibacterial Therapy

Antibacterial therapy in infants and children presents many challenges. A daunting problem is the paucity of pediatric data regarding pharmacokinetics and optimal dosages; pediatric recommendations are therefore (unfortunately) extrapolated from studies in adults. A 2nd challenge is the need for the clinician to consider important differences among various age groups with respect to the pathogenic species responsible for pediatric bacterial infections. Age-appropriate antibiotic dosing and toxicities must also be considered, taking into account the developmental status and physiology of infants and children. Finally, the style of usage of antibiotics has some important differences compared with usage in adult patients. Specific antibiotic therapy is optimally driven by a microbiologic diagnosis, predicated on isolation of the pathogenic organism from a sterile body site, and supported by antimicrobial susceptibility testing. Given the inherent difficulties that can arise in collecting specimens from pediatric patients, and given the increased risk of serious bacterial infection in young infants, 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 information 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, in turn affecting the choice, dosing, and degree of urgency of administration of antimicrobial agents. The vaccination history may reflect reduced risk for some invasive infections, but not necessarily elimination of risk. The risk of serious bacterial infection in pediatric practice is also affected by the child’s immunologic status, which may be compromised by immaturity (neonates), underlying disease, and associated treatments (Chapter 171). 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 (Chapter 172). The likelihood of central nervous system (CNS) involvement must be considered in all pediatric patients, because many of the more common 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 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 173-1 and 173-2). 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 bypassing the antimicrobial site of action.

Table 173-1 MECHANISMS OF RESISTANCE TO β-LACTAM ANTIBIOTICS

III Decrease concentration of β-lactam antibiotic inside cell

A Restrict its entry (loss of porins)

B Pump it out (efflux mechanisms)

Table 173-2 AMINOGLYCOSIDE-MODIFYING ENZYMES

ENZYMES	USUAL ANTIBIOTICS MODIFIED	COMMON GENERA
PHOSPHORYLATION
APH(2″)	K, T, G	SA, SR
APH(3′)-I	K	E, PS, SA, SR
APH(3′)-III	K, ±A	E, PS, SA, SR
ACETYLATION
AAC(2′)	G	PR
AAC(3)-I	±T, G	E, PS
AAC(3)-III, -IV, OR-V	K, T, G	E, PS
AAC(6′)	K, T, A	E, PS, SA
ADENYLATION
ANT(2″)	K, T, GE, PS
ANT(4′)	K, T, A	SA

A, amikacin; AAC, aminoglycoside acetyltransferase; ANT, aminoglycoside nucleotidyltransferase; APH, aminoglycoside phosphotransferase; E, Enterobacteriaceae; G, gentamicin; K, karamycin; PR, Providencia-Proteus; PS, pseudomonads; SA, staphylococci; SR, streptococci; T, tobramycin.

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. 173-1). 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. 173-2).

Figure 173-1 The area under the curve (shaded area) for different antibiotics. The area under the curve provides a measure of antibiotic exposure to bacterial pathogens. The greatest exposure comes with antibiotics that have a long serum half-life and are administered parenterally (upper left panel, antibiotic A). The lowest exposure occurs with oral administration (lower right panel, antibiotic C). Dosing of antibiotic B once a day (upper right panel) provides far less exposure than dosing the same antibiotic every 6 hr (lower left panel). MIC, minimal inhibitory concentration.

(From Pong AL, Bradley JS: Guidelines for the selection of antibacterial therapy in children, Pediatr Clin North Am 52:869–894, 2005.)

Figure 173-2 Antibacterial effects of antibiotic combinations. Left: Curve of A + B illustrates synergism (increased killing). Center: Curve of C + D illustrates antagonism (D is less effective when C is added). Right: Curve of E + F illustrates indifference, or additive effect (addition of E to F has no effect on F).

(From Mandell GL, Bennett JE, Dolin R, editors: Principles and practice of infectious diseases, vol 1, ed 6, Philadelphia, 2005, Elsevier, p 247.)

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, 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.

Antibiotics Commonly Used in Pediatric Practice (Table 173-3)

Table 173-3 ANTIBACTERIAL MEDICATIONS (ANTIBIOTICS)

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DRUG (TRADE NAMES, FORMULATIONS)	INDICATIONS (MECHANISM OF ACTION) AND DOSING	COMMENTS
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.	Cautions: Anaerobes, Streptococcus (including S. pneumoniae) are resistant. May cause ototoxicity and nephrotoxicity. Monitor renal function. Drug eliminated renally. Administered IV over 30-60 min.
	Neonates: Postnatal age ≤7 days: 1,200-2,000 g: 7.5 mg/kg q 12-18 hr IV or IM; >2,000 g: 10 mg/kg q 12 hr IV or IM; postnatal age >7 days: 1,200-2,000 g IV or IM: 7.5 mg/kg q 8-12 hr IV or IM; >2,000 g: 10 mg/kg q 8 hr IV or IM.	Drug interactions: May potentiate other ototoxic and nephrotoxic drugs. Target serum concentrations: Peak 25-40 mg/L; trough <10 mg/L.
	Children: 15-25 mg/kg/24 hr divided q 8-12 hr IV or IM.
	Adults: 15 mg/kg 24 hr divided q 8-12 hr IV or IM.
Amoxicillin Amoxil, Polymox. Capsule: 250, 500 mg.	Penicillinase-susceptible β-lactam: gram-positive pathogens except Staphylococcus; Salmonella, Shigella, Neisseria, E. coli, and Proteus mirabilis.	Cautions: Rash, diarrhea, abdominal cramping. Drug eliminated renally. Drug interaction: Probenecid.
Tablet: chewable: 125, 250 mg. Suspension: 125 mg/5 mL, 250 mg/5 mL.	Children: 20-50 mg/kg/24 hr divided q 8-12 hr PO. Higher dose of 80-90 mg/kg 24 hr PO for otitis media.
Drops: 50 mg/mL.	Adults: 250-500 mg q 8-12 hr PO.
Drops: 50 mg/mL.	Uncomplicated gonorrhea: 3 g with 1 g probenecid PO.
Amoxicillin-clavulanate Augmentin. Tablet: 250, 500, 875 mg. Tablet, chewable: 125, 200, 250, 400 mg. Suspension: 125 mg/5 mL, 200 mg/5 mL, 250 mg/5 mL, 400 mg/5 mL.	β-Lactam (amoxicillin) and β-lactamase inhibitor (clavulanate) enhances amoxicillin activity against penicillinase-producing bacteria. S. aureus (not methicillin-resistant organism), Streptococcus, Haemophilus influenzae, Moraxella catarrhalis, E. coli, Klebsiella, Bacteroides fragilis.	Cautions: Drug dosed on amoxicillin component. May cause diarrhea, rash. Drug eliminated renally. Drug interaction: Probenecid. Comment: Higher dose may be active against penicillin tolerant/resistant S. pneumoniae.
	Neonates: 30 mg/kg/24 hr divided q 12 hr PO.
	Children: 20-45 mg/kg 24 hr divided q 8-12 hr PO. Higher dose 80-90 mg/kg/24 hr PO for otitis media.
Ampicillin Polycillin, Omnipen. Capsule: 250, 500 mg. Suspension: 125 mg/5 mL, 250 mg/5 mL, 500 mg/5 mL. Injection.	β-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 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).	Cautions: Less bioavailable than amoxicillin, causing greater diarrhea. Drug interaction: Probenecid.
	Children: 100-200 mg/kg/24 hr divided q 6 hr IV or IM (meningitis: 200-400 mg/kg/24 hr divided q 4-6 hr IV or IM).
	Adults: 250-500 mg q 4-8 hr IV or IM.
Ampicillin-sulbactam Unasyn. Injection.	β-Lactam (ampicillin) and β-lactamase inhibitor (sulbactam) enhances ampicillin activity against penicillinase-producing bacteria: S. aureus, H. influenzae, M. catarrhalis, E. coli, Klebsiella, B. fragilis.	Cautions: Drug dosed on ampicillin component. May cause diarrhea, rash. Drug eliminated renally. Note: Higher dose may be active against penicillin-tolerant/resistant S. pneumoniae.
	Children: 100-200 mg/kg/24 hr divided q 4-8 hr IV or IM.	Drug interaction: Probenecid.
	Adults: 1-2 g q 6-8 hr IV or IM (max daily dose: 8 g).
Azithromycin Zithromax. Tablet: 250 mg. Suspension: 100 mg/5 mL, 200 mg/5 mL.	Azalide antibiotic with activity against S. aureus, Streptococcus, H. influenzae, Mycoplasma, Legionella, Chlamydia trachomatis. Children: 10 mg/kg PO on day 1 (max dose: 500 mg) followed by 5 mg/kg PO q 24 hr for 4 days. Group A streptococcus pharyngitis: 12 mg/kg/24 hr PO (max dose: 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.	Note: Very long half-life permitting once-daily dosing. No metabolic-based drug interactions (unlike erythromycin and clarithromycin), limited gastrointestinal distress. Shorter-course regimens (e.g., 1-3 days) under investigation. 3-day, therapy (10 mg/kg/24 hr × 3 days) and single-dose therapy (30 mg/kg): use with increasing frequency (not for streptococcus pharyngitis).
Aztreonam Azactam.	β-Lactam (monobactam) antibiotic with activity against gram-negative aerobic bacteria, Enterobacteriaceae, and Pseudomonas aeruginosa.	Cautions: Rash, thrombophlebitis, eosinophilia. Renally eliminated. Drug interaction: Probenecid.
Injection.	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 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 6-8 hr IV or IM.
	Children: 90-120 mg/kg/24 hr divided q 6-8 hr IV or IM. For cystic fibrosis up to 200 mg/kg/24 hr IV.
	Adults: 1-2 g IV or IM q 8-12 hr (max dose: 8 g/24 hr).
Carbenicillin Geopen Injection. Geocillin oral tablet.	Extended-spectrum penicillin (remains susceptible to penicillinase destruction) active against Enterobacter, indole-positive Proteus, and Pseudomonas.	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.
	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: 300-400 mg/kg/24 hr divided q 6 hr IV or IM.
	Children: 400-600 mg/kg/24 hr divided q 4-6 hr IV or IM.
Cefaclor Ceclor. Capsule: 250, 500 mg.	2nd generation cephalosporin active against S. aureus, Streptococcus including S. pneumoniae, H. influenzae, E. coli, Klebsiella, and Proteus.	Cautions: β-Lactam safety profile (rash, eosinophilia) with high incidence of serum sickness reaction. Renally eliminated. Drug interaction: Probenecid.
Suspension: 125 mg/5 mL, 187 mg/5 mL, 250 mg/5 mL, 375 mg/5 mL.	Children: 20-40 mg/kg/24 hr divided q 8-12 hr PO (max dose: 2 g). Adults: 250-500 mg q 6-8 hr PO.
Cefadroxil Duricef, Ultracef.	1st-generation cephalosporin active against S. aureus, Streptococcus, E. coli, Klebsiella, and Proteus.	Cautions: β-Lactam safety profile (rash, eosinophilia). Renally eliminated. Long half-life permits q 12-24 hr dosing.
Capsule: 500 mg.	Children: 30 mg/kg/24 hr divided q 12 hr PO (max dose: 2 g).	Drug interaction: Probenecid.
Tablet: 1,000 mg.
Suspension: 125 mg/5 mL, 250 mg/5 mL, 500 mg/5 mL.	Adults: 250-500 mg q 8-12 hr PO.
Cefazolin Ancef, Kefzol.	1st generation cephalosporin active against S. aureus, Streptococcus, E. coli, Klebsiella, and Proteus.	Caution: β-Lactam safety profile (rash, eosinophilia). Renally eliminated. Does not adequately penetrate CNS.
Injection.	Neonates: Postnatal age ≤7 days 40 mg/kg/24 hr divided q 12 hr IV or IM; >7 days 40-60 mg/kg/24 hr divided q 8 hr IV or IM.	Drug interaction: Probenecid.
	Children: 50-100 mg/kg/24 hr divided q 8 hr IV or IM.
	Adults: 0.5-2g q 8 hr IV or IM (max dose: 12 g/24 hr).
Cefdinir Omnicef. Capsule: 300 mg. Oral suspension: 125 mg/5 mL.	Extended-spectrum, semi-synthetic cephalosporin. Children 6 mo-12 yr: 14 mg/kg/24 hr in 1 or 2 doses PO (max dose: 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 iron-containing 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 gram-positive and gram-negative pathogens, including Pseudomonas aeruginosa* many multidrug-resistant pathogens.**	Adverse events: Diarrhea, nausea, vaginal candidiasis Cautions: β-Lactam safety profile (rash, eosinophilia). Renally eliminated.
	Children: 100-150 mg/kg/24 hr q 8-12 hr IV or IM.	Drug interaction: Probenecid.
	Adults: 2-4 g/24 hr q 12 hr IV or IM.
Cefixime Suprax. Tablet: 200, 400 mg.	3rd generation cephalosporin active against Streptococci, H. influenzae, M. catarrhalis, Neisseria gonorrhoeae, Serratia marcescens, and P. vulgaris. No antistaphylococcal or antipseudomonal activity.	Cautions: β-Lactam safety profile (rash, eosinophilia). Renally eliminated. Does not adequately penetrate CNS. Drug interaction: Probenecid.
Suspension: 100 mg/5 mL.	Children: 8 mg/kg/24 hr divided q 12-24 hr PO.
Suspension: 100 mg/5 mL.	Adults: 400 mg/24 hr divided q 12-24 hr PO.
Cefoperazone sodium Cefobid. Injection.	3rd generation cephalosporin active against many gram-positive and gram-negative pathogens. Neonates: 100 mg/kg/24 hr divided q 12 hr IV or IM. Children: 100-150 mg/kg/24 hr divided q 8-12 hr IV or IM. Adults: 2-4 g/24 hr divided q 8-12 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; >12,000 g: 150 mg/kg/24 hr divided q 8 hr IV or IM.	Cautions: β-Lactam safety profile (rash, eosinophilia). Renally eliminated. Each gram of drug contains 2.2 mEq sodium. Active metabolite. Drug interaction: Probenecid.
	Children: 150 mg/kg/24 hr divided q 6-8 hr IV or IM (meningitis: 200 mg/kg/24 hr divided q 6-8 hr IV).
	Adults: 1-2 g q 8-12 hr IV or IM (max dose: 12 g/24 hr).
Cefotetan disodium Cefotan. Injection.	2nd generation cephalosporin active against S. aureus, Streptococcus, H. influenzae, E. coli, Klebsiella, Proteus, and Bacteroides. Inactive against Enterobacter. Children: 40-80 mg/kg/24 hr divided IV or IM q 12 hr.	Cautions: Highly protein-bound cephalosporin, poor CNS penetration; β-Lactam safety profile (rash, eosinophilia), disulfiram-like reaction with alcohol. Renally eliminated (∼20% in bile).
Cefotetan disodium Cefotan. Injection.	Adults: 2-4 g/24 hr divided q 12 hr IV or IM (max dose: 6 g/24 hr).
Cefoxitin sodium Mefoxin. Injection.	2nd generation cephalosporin active against S. aureus, Streptococcus, H. influenzae, E. coli, Klebsiella, Proteus, and Bacteroides. Inactive against Enterobacter.	Cautions: Poor CNS penetration; β-Lactam safety profile (rash, eosinophilia). Renally eliminated. Painful given intramuscularly.
	Neonates: 70-100 mg/kg/24 hr divided q 8-12 hr IV or IM.	Drug interaction: Probenecid.
	Children: 80-160 mg/kg/24 hr divided q 6-8 hr IV or IM.
	Adults: 1-2 g q 6-8 hr IV or IM (max dose: 12 g/24 hr).
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: 200-800 mg/24 hr divided q 12 hr PO (max dose: 800 mg/24 hr). Uncomplicated gonorrhea: 200 mg PO as single-dose therapy.	Cautions: β-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 8-12 hr PO. Adults: 500-1,000 mg/24 hr divided q 12 hr PO (max dose: 1.5 g/24 hr).	Cautions: β-Lactam safety profile (rash, eosinophilia). Renally eliminated. Good bioavailability; food does not affect bioavailability. Drug interaction: Probenecid.
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 days ≤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: 1-2 g q 8-12 hr IV or IM (max dose: 8-12 g/24 hr).	Cautions: β-Lactam safety profile (rash, eosinophilia). Renally eliminated. Increasing pathogen resistance developing with long-term, 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 6-8 hr IV or IM. Adults: 1-2 g q 6-8 hr IV or IM (max dose: 12 g/24 hr).