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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; as a consequence, pediatric recommendations are frequently extrapolated from adult studies. A 2nd challenge is the need for the clinician to consider important differences among pediatric age-groups with respect to the pathogenic species most often responsible for bacterial infections. Age-appropriate antibiotic dosing and toxicities must be considered, taking into account the developmental status and physiology of infants and children. Finally, the style of how a pediatrician uses antibiotics in children, particularly young infants, has some important differences compared with how antibiotics are used 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. However, given the inherent difficulties that can arise in collecting specimens from pediatric patients, and given the high risk of mortality and disability associated with serious bacterial infections in very young infants, much of pediatric infectious diseases practice is based on a clinical diagnosis with empirical use of antibacterial agents, administered before or even without eventual identification of the specific pathogen. Although there is increasing emphasis on the importance of using empirical therapy sparingly (so as to not select for resistant organisms), there are some settings in which antimicrobials must be administered before the presence of a specific bacterial pathogen is proven. This is particularly relevant to the care of the febrile or ill-appearing neonate or young infant under 30 days of age.
Several key considerations influence decision-making regarding 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, information that in turn affects the choice, dosing, and degree of urgency of administration of antimicrobial agents. The vaccination history may confer reduced risk for some invasive infections (i.e., Haemophilus influenzae type b, Streptococcus pneumoniae , Neisseria meningitidis ), 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 (see Chapter 205 ). Infections in immunocompromised children may result from bacteria that are not considered pathogenic in immunocompetent children. The presence of foreign bodies (medical devices) also increases the risk of bacterial infections (see Chapter 206 ). The likelihood of central nervous system (CNS) involvement must be considered in all pediatric patients with serious bacterial infections, because many cases of bacteremia in childhood 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 covered must also be considered. Resistance to penicillin and cephalosporins is commonplace among strains of S. pneumoniae, often necessitating the use of other classes of antibiotics. Similarly, the striking emergence of community-acquired methicillin-resistant Staphylococcus aureus ( MRSA ) infections has complicated antibiotic choices for this pathogen. Extended-spectrum β-lactamase ( ESBL )–producing gram-negative bacteria (Enterobacteriaceae) have reduced the effectiveness of penicillins and cephalosporins. Furthermore, carbapenem-resistant Enterobacteriaceae are an increasing problem among hospitalized patients, particularly in children with an epidemiologic connection to regions of the world, such as India, where such strains are frequently encountered.
Antimicrobial resistance occurs through many modifications of the bacterial genome ( Tables 207.1 and 207.2 ). 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, and bypassing the antimicrobial site of action.
Table 207.1
Mechanisms of Resistance to β-Lactam Antibiotics
Adapted from Opal SM, Pop-Vicas A: Molecular mechanisms of antibiotic resistance in bacteria. In Bennett JF, Dolin R, Blaser MJ, editors: Mandell, Douglas, and Bennett's principles and practice of infectious diseases, ed 8, Philadelphia, 2015, Elsevier (Table 18-4).
|
ESBLs, Extended-spectrum β-lactamases; PBP, Penicillin-binding protein.
Table 207.2
Aminoglycoside-Modifying Enzymes *
Adapted from Opal SM, Pop-Vicas A: Molecular mechanisms of antibiotic resistance in bacteria. In Bennett JF, Dolin R, Blaser MJ, editors: Mandell, Douglas, and Bennett's principles and practice of infectious diseases, ed 8, Philadelphia, 2015, Elsevier (Table 18-5).
| 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, G | E, PS |
| ANT(4′) | K, T, A | SA |
| BIFUNCTIONAL ENZYMES | ||
| AAC(6′)-APH(2″) | G, Ar | SA, Ent |
| AAC(6′)-lbcr | G, K, T, FQ * | E |
A, Amikacin; AAC, aminoglycoside acetyltransferase; ANT, aminoglycoside nucleotidyltransferase; APH, aminoglycoside phosphotransferase; cr, ciprofloxacin resistance; Ar, arbekacin, E, Enterobacteriaceae; Ent, enterococci, FQ, fluoroquinolone (acetylates the piperazine ring in some fluoroquinolones), G, gentamicin; K, kanamycin; PR, Providencia-Proteus ; PS, pseudomonads; SA, staphylococci; SR, streptococci; T, tobramycin.
* Aminoglycoside-modifying enzymes confer antibiotic resistance through 3 general reactions: N-acetylation, O-nucleotidylation, and O-phosphorylation. For each of these general reactions, there are several different enzymes that attack a specific amino or hydroxyl group.
Antimicrobial resistance has reached crisis proportions , driven by the emergence of new resistance mechanisms (e.g., carbapenemases, including Klebsiella pneumoniae –associated carbapenemases, or KPCs ) and by overuse of antibiotics, both in healthcare and in other venues, such as agribusiness and animal husbandry. This increase in antibiotic resistance has rendered some bacterial infections encountered in clinical practice virtually untreatable. Accordingly, there is an urgent need to develop new antimicrobials, as well as rediscover some older antibiotics that have been out of use in recent decades but still retain activity against resistant organisms. It is vital that practitioners use antibiotics only as necessary, with the narrowest feasible antimicrobial spectrum, to help thwart emergence of resistance. In addition, advocacy for vaccines , particularly conjugate pneumococcal vaccine, can also decrease the selective pressure that excessive antimicrobial use exerts on resistance.
Effective antibiotic action requires achieving therapeutic levels of the drug 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 this level as a surrogate marker for achievement of 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. 207.1 ). These levels in turn are 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. 207.2 ).
Area under the curve (AUC; shaded area ) for different antibiotics.
The AUC 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.)
Antibacterial effects of antibiotic combinations.
A, Combination of antibiotics 1 and 2 is indifferent ; killing by antibiotic 2 is unchanged when antibiotic 1 is added. B, Combination of antibiotics 1 and 2 results in synergy ; killing by antibiotic 2 is significantly enhanced when antibiotic 1 is added at a subinhibitory concentration. C, Combination of antibiotics 1 and 2 is antagonistic ; killing by antibiotic 2 is diminished in the presence of antibiotic 1.
(From Eliopoulos GM, Moellering RC Jr: Principles of anti-infective therapy. In Bennett JF, Dolin R, Blaser MJ, editors: Mandell, Douglas, and Bennett's principles and practice of infectious diseases, ed 8, Philadelphia, 2015, Elsevier, Fig 17-1.)
Age- and Risk-Specific Use of Antibiotics in Children
Neonates
The causative pathogens associated with neonatal infections are typically acquired around the time of delivery. Thus, empirical antibiotic selection must take into account the importance of these organisms (see Chapter 129 ). Among the causes of neonatal sepsis in infants, group B streptococcus (GBS) is the most common. Although intrapartum antibiotic prophylaxis administered to women at increased risk for transmission of GBS to the infant has greatly decreased the incidence of this infection in neonates, particularly with respect to early-onset disease, GBS infections are still frequently encountered in clinical practice (see Chapter 211 ). Gram-negative enteric organisms acquired from the maternal birth canal, in particular Escherichia coli, are also common causes of neonatal sepsis. Although less common, Listeria monocytogenes is an important pathogen to consider, insofar as the organism is intrinsically resistant to cephalosporin antibiotics, which are often used as empirical therapy for serious bacterial infections in young children. Salmonella bacteremia and meningitis on a global basis is a well-recognized infection in infants. All these organisms can be associated with meningitis in the neonate; therefore lumbar puncture should always be considered with 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 ( Hib ; see Chapter 221 ). With the advent of conjugate vaccines against Hib, invasive disease has declined dramatically. However, outbreaks still occur, and have been observed in the context of parental refusal of vaccines. Therefore, it is still important to use antimicrobials that are active against Hib in many clinical settings, particularly if meningitis is a consideration. Other important pathogens to consider in this age-group include E. coli , S. pneumoniae, N. meningitidis, 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 children in the outpatient setting. Resistance of S. pneumoniae as well as MRSA is a result of mutations that confer alterations in penicillin-binding proteins, the molecular targets of penicillin and cephalosporin activity (see Table 207.1 ).
Depending on the specific clinical diagnosis, other pathogens encountered among older children include Moraxella catarrhalis, nontypeable (nonencapsulated) 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; viridians group streptococci and Enterococcus, which cause endocarditis; and Salmonella spp., which cause enteritis, bacteremia, osteomyelitis, and septic arthritis. Vector-borne bacterial infections, including Borrelia burgdorferi , Rickettsia rickettsii , and Anaplasma phagocytophilum , are increasingly recognized in certain regions, with an evolving epidemiology triggered by climate change. These complexities underscore the importance of formulation of a complete differential diagnosis in children with suspected severe bacterial infections, including an assessment of the severity of the infection undertaken in parallel with consideration of local epidemiological disease trends, including knowledge of the antimicrobial 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). Serious viral infections, particularly influenza, can also predispose to invasive bacterial infections, especially those caused by S. aureus . 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 caused by highly antibiotic-resistant gram-negative enteric organisms. In addition to bacterial pathogens already discussed, Pseudomonas aeruginosa and enteric organisms, including E. coli, K. pneumoniae, Enterobacter, and Serratia , are important 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 because of ESBLs (see Table 207.1 ). Class B metallo-β-lactamases (also known as New Delhi metallo-β-lactamases) that hydrolyze all β-lactam antibiotics except aztreonam are increasingly being described, as well as KPCs that confer resistance to carbapenems. Reports of carbapenemases are increasingly being described for Enterobacteriaceae. Carbapenemase-producing Enterobacteriaceae are different from other multidrug-resistant microorganisms in that they are susceptible to few (if any) antibacterial agents.
Other modes of antimicrobial resistance are being increasingly recognized. 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 E. faecium are inherently difficult to treat. These organisms may cause urinary tract infection (UTI) 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 bacteria.
Infections Associated With Medical Devices
A special situation affecting antibiotic use is the presence of an indwelling medical device, such as venous catheter, ventriculoperitoneal shunts, stents, or other catheters (see Chapter 206 ). In addition to S. aureus, coagulase-negative staphylococci are also a major consideration. Coagulase-negative staphylococci seldom cause serious disease in the absence of risk factors such as indwelling catheters. Empirical antibiotic regimens must take this risk into consideration. In addition to appropriate antibiotic therapy, removal or replacement of the colonized prosthetic material is usually required for cure.
Antibiotics Commonly Used in Pediatric Practice
Table 207.3 lists antibiotic medications and pediatric indications.
Table 207.3
Selected Antibacterial Medications (Antibiotics) *
| 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 Neonates: Postnatal age ≤7 days, weight 1,200-2,000 g: 7.5 mg/kg q12-18h IV or IM; weight >2,000 g: 10 mg/kg q12h IV or IM; postnatal age >7 days, weight 1,200-2,000 g: 7.5 mg/kg q8-12h IV or IM; weight >2,000 g: 10 mg/kg q8h IV or IM Children: 15-25 mg/kg/24 hr divided q8-12h IV or IM Adults: 15 mg/kg/24 hr divided q8-12h IV or IM |
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 Drug interactions: May potentiate other ototoxic and nephrotoxic drugs Target serum 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 |
Penicillinase-susceptible β-lactam: gram-positive pathogens except Staphylococcus; Salmonella, Shigella, Neisseria, E. coli , and Proteus mirabilis Children: 20-50 mg/kg/24 hr divided q8-12h PO. Higher dose of 80-90 mg/kg 24 hr PO for otitis media Adults: 250-500 mg q8-12h 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 Suspension: 125 mg/5 mL, 200 mg/5 mL, 250 mg/5 mL, 400 mg/5 mL |
β-Lactam (amoxicillin) combined with 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 Neonates: 30 mg/kg/24 hr divided q12h PO Children: 20-45 mg/kg 24 hr divided q8-12h PO. Higher dose 80-90 mg/kg/24 hr PO for otitis media |
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 |
| 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 weight ≤2,000 g: 50 mg/kg/24 hr IV or IM q12h (meningitis: 100 mg/kg/24 hr divided q12h IV or IM); weight >2,000 g: 75 mg/kg/24 hr divided q8h IV or IM (meningitis: 150 mg/kg/24 hr divided q8h IV or IM). Postnatal age >7 days weight <1,200 g: 50 mg/kg/24 hr IV or IM q12h (meningitis: 100 mg/kg/24 hr divided q12h IV or IM); weight 1,200-2,000 g: 75 mg/kg/24 hr divided q8h IV or IM (meningitis: 150 mg/kg/24 hr divided q8hr IV or IM); weight >2,000 g: 100 mg/kg/24 hr divided q6h IV or IM (meningitis: 200 mg/kg/24 hr divided q6h IV or IM) Children: 100-200 mg/kg/24 hr divided q6h IV or IM (meningitis: 200-400 mg/kg/24 hr divided q4-6h IV or IM) Adults: 250-500 mg q4-8h IV or IM |
Cautions: Less bioavailable than amoxicillin, causing greater diarrhea Drug interaction: Probenecid |
| 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 Children: 100-200 mg/kg/24 hr divided q4-8h IV or IM Adults: 1-2 g q6-8h 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 penicillin-tolerant/resistant S. pneumoniae Drug interaction: Probenecid |
| 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, Babesia microti Children: 10 mg/kg PO on day 1 (max dose: 500 mg) followed by 5 mg/kg PO q24h 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 GI 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 Injection |
β-Lactam (monobactam) antibiotic with activity against gram-negative aerobic bacteria, Enterobacteriaceae, and Pseudomonas aeruginosa Neonates: Postnatal age ≤7 days weight ≤2,000 g: 60 mg/kg/24 hr divided q12h IV or IM; weight >2,000 g: 90 mg/kg/24 hr divided q8h IV or IM; postnatal age >7 days weight <1,200 g: 60 mg/kg/24 hr divided q12h IV or IM; weight 1,200-2,000 g: 90 mg/kg/24 hr divided q8h IV or IM; weight >2,000 g: 120 mg/kg/24 hr divided q6-8h IV or IM Children: 90-120 mg/kg/24 hr divided q6-8h IV or IM. For cystic fibrosis, up to 200 mg/kg/24 hr IV Adults: 1-2 g IV or IM q8-12h (max dose: 8 g/24 hr) |
Cautions: Rash, thrombophlebitis, eosinophilia. Renally eliminated Drug interaction: Probenecid |
| Cefadroxil Generic 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 q12h PO (max dose: 2 g) Adults: 250-500 mg q8-12h PO |
Cautions: β-Lactam safety profile (rash, eosinophilia). Renally eliminated. Long half-life permits q12-24h dosing Drug interaction: Probenecid |
| Cefazolin Ancef, Kefzol Injection |
First-generation cephalosporin active against S. aureus, Streptococcus, E. coli, Klebsiella , and Proteus Neonates: Postnatal age ≤7 days 40 mg/kg/24 hr divided q12h IV or IM; >7 days 40-60 mg/kg/24 hr divided q8h IV or IM Children: 50-100 mg/kg/24 hr divided q8h IV or IM Adults: 0.5-2g q8h IV or IM (max dose: 12 g/24 hr) |
Caution: β-Lactam safety profile (rash, eosinophilia). Renally eliminated. Does not adequately penetrate CNS Drug interaction: Probenecid |
| Cefdinir Omnicef Capsule: 300 mg Oral suspension: 125 mg/5 mL |
Extended-spectrum, semisynthetic 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 q24h 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, fourth-generation cephalosporin active against many gram-positive and gram-negative pathogens, including P. aeruginosa and many multidrug-resistant pathogens Children: 100-150 mg/kg/24 hr q8-12h IV or IM Adults: 2-4 g/24 hr q12h IV or IM |
Adverse events: Diarrhea, nausea, vaginal candidiasis Cautions: β-lactam safety profile (rash, eosinophilia). Renally eliminated Drug interaction: Probenecid |
| Cefixime Suprax Tablet: 200, 400 mg Suspension: 100 mg/5 mL |
Third-generation cephalosporin active against streptococci, H. influenzae, M. catarrhalis, Neisseria gonorrhoeae, Serratia marcescens , and Proteus vulgaris . No antistaphylococcal or antipseudomonal activity Children: 8 mg/kg/24 hr divided q12-24h PO Adults: 400 mg/24 hr divided q12-24h PO |
Cautions: β-Lactam safety profile (rash, eosinophilia). Renally eliminated. Does not adequately penetrate CNS Drug interaction: Probenecid |
| Cefoperazone sodium Cefobid Injection |
Third-generation cephalosporin active against many gram-positive and gram-negative pathogens Neonates: 100 mg/kg/24 hr divided q12h IV or IM Children: 100-150 mg/kg/24 hr divided q8-12h IV or IM Adults: 2-4 g/24 hr divided q8-12h 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 |
Third-generation cephalosporin active against Gram-positive and Gram-negative pathogens. No antipseudomonal activity Neonates: ≤7 days: 100 mg/kg/24 hr divided q12h IV or IM; >7 days: weight <1,200 g 100 mg/kg/24 hr divided q12h IV or IM; weight >1,200 g: 150 mg/kg/24 hr divided q8h IV or IM Children: 150 mg/kg/24 hr divided q6-8h IV or IM (meningitis: 200 mg/kg/24 hr divided q6-8h IV) Adults: 1-2 g q8-12h IV or IM (max dose: 12 g/24 hr) |
Cautions: β-Lactam safety profile (rash, eosinophilia). Renally eliminated. Each gram of drug contains 2.2 mEq sodium. Active metabolite Drug interaction: Probenecid |
| Cefotetan disodium Cefotan Injection |
Second-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 q12h IV or IM Adults: 2-4 g/24 hr divided q12h IV or IM (max dose: 6 g/24 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) |
| Cefoxitin sodium Mefoxin Injection |
Second-generation cephalosporin active against S. aureus, Streptococcus, H. influenzae, E. coli, Klebsiella, Proteus , and Bacteroides . Inactive against Enterobacter Neonates: 70-100 mg/kg/24 hr divided q8-12h IV or IM Children: 80-160 mg/kg/24 hr divided q6-8h IV or IM Adults: 1-2 g q6-8h IV or IM (max dose: 12 g/24 hr) |
Cautions: Poor CNS penetration; β-lactam safety profile (rash, eosinophilia). Renally eliminated. Painful given intramuscularly Drug interaction: Probenecid |
| Cefpodoxime proxetil Vantin Tablet: 100 mg, 200 mg Suspension: 50 mg/5 mL, 100 mg/5 mL |
Third-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 q12h PO Adults: 200-800 mg/24 hr divided q12h 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 |
| Ceftaroline fosamil Teflaro Injection |
Fifth-generation cephalosporin active against S. aureus (including MRSA when used for skin and soft tissue infection), Streptococcus pyogenes, Streptococcus agalactiae, Escherichia coli, Klebsiella pneumoniae, H. influenzae, and Klebsiella oxytoca Children: skin/skin structure infections or community-acquired pneumonia, 24 mg/kg/24 hr divided q8h IV (2-23 mo old) ×5-14 days; 36 mg/kg/24 hr divided q8h IV (weight ≤33 kg) ×5-14 days; 400 mg q8h IV (weight >33 kg) Adults: 600 mg q12h IV |
Caution: β-Lactam safety profile (rash, eosinophilia) Drug interaction: Probenecid |
| Cefprozil Cefzil Tablet: 250, 500 mg Suspension: 125 mg/5 mL, 250 mg/5 mL |
Second-generation cephalosporin active against S. aureus, Streptococcus, H. influenzae, E. coli, M. catarrhalis, Klebsiella , and Proteus spp. Children: 30 mg/kg/24 hr divided q8-12h PO Adults: 500-1,000 mg/24 hr divided q12h 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, Tazicef, Tazidime Injection |
Third-generation cephalosporin active against gram-positive and gram-negative pathogens, including P. aeruginosa Neonates: Postnatal age ≤7 days: 100 mg/kg/24 hr divided q12h IV or IM; >7 days weight ≤1,200 g: 100 mg/kg/24 hr divided q12h IV or IM; weight >1,200 g: 150 mg/kg/24 hr divided q8h IV or IM Children: 150 mg/kg/24 hr divided q8h IV or IM (meningitis: 150 mg/kg/24 hr IV divided q8h) Adults: 1-2 g q8-12h 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 |
| Ceftizoxime Cefizox Injection |
Third-generation cephalosporin active against gram-positive and gram-negative pathogens. No antipseudomonal activity Children: 150 mg/kg/24 hr divided q6-8h IV or IM Adults: 1-2 g q6-8h IV or IM (max dose: 12 g/24 hr) |
Cautions: β-Lactam safety profile (rash, eosinophilia). Renally eliminated Drug interaction: Probenecid |
| Ceftriaxone sodium Rocephin Injection |
Third-generation cephalosporin widely active against gram-positive and gram-negative pathogens. No antipseudomonal activity Neonates: 50-75 mg/kg q24h IV or IM Children: 50-75 mg/kg q24h IV or IM (meningitis: 75 mg/kg dose once then 80-100 mg/kg/24 hr divided q12-24h IV or IM) Adults: 1-2 g q24h IV or IM (max dose: 4 g/24 hr) |
Cautions: β-Lactam safety profile (rash, eosinophilia). Eliminated via kidney (33–65%) and bile; can cause sludging. Long half-life and dose-dependent protein binding favors q24h rather than q12h dosing. Can add 1% lidocaine for IM injection Drug interaction: Probenecid. In neonates, co-administration with calcium-containing products can result in severe precipitation and attendant embolic complications |
| Cefuroxime (cefuroxime axetil for oral administration) Ceftin, Kefurox, Zinacef Injection Suspension: 125 mg/5 mL Tablet: 125, 250, 500 mg |
Second-generation cephalosporin active against S. aureus, Streptococcus, H. influenzae, E. coli, M. catarrhalis, Klebsiella , and Proteus Neonates: 40-100 mg/kg/24 hr divided q12h IV or IM Children: 200-240 mg/kg/24 hr divided q8h IV or IM; PO administration: 20-30 mg/kg/24 hr divided q8-12h PO Adults: 750-1,500 mg q8h IV or IM (max dose: 6 g/24 hr) |
Cautions: β-Lactam safety profile (rash, eosinophilia). Renally eliminated. Food increases PO bioavailability Drug interaction: Probenecid |
| 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 |
First-generation cephalosporin active against S. aureus, Streptococcus, E. coli, Klebsiella , and Proteus Children: 25-100 mg/kg/24 hr divided q6-8h PO Adults: 250-500 mg q6h PO (max dose: 4 g/24 hr) |
Cautions: β-Lactam safety profile (rash, eosinophilia). Renally eliminated Drug interaction: Probenecid |
| Cephradine Velosef Capsule: 250, 500 mg Suspension: 125 mg/5 mL, 250 mg/5 mL |
First-generation cephalosporin active against S. aureus, Streptococcus, E. coli, Klebsiella , and Proteus Children: 50-100 mg/kg/24 hr divided q6-12h PO Adults: 250-500 mg q6-12h PO (max dose: 4 g/24 hr) |
Cautions: β-Lactam safety profile (rash, eosinophilia). Renally eliminated Drug interaction: Probenecid |
| Ciprofloxacin Cipro Tablet: 100, 250, 500, 750 mg Injection Ophthalmic solution and ointment Otic suspension Oral suspension: 250 and 500 mg/5 mL |
Quinolone antibiotic active against P. aeruginosa, Serratia, Enterobacter, Shigella, Salmonella, Campylobacter, N. gonorrhoeae, H. influenzae, M. catarrhalis, some S. aureus , and some Streptococcus Neonates: 10 mg/kg q 12 hr PO or IV Children: 15-30 mg/kg/24 hr divided q12h PO or IV; cystic fibrosis: 20-40 mg/kg/24 hr divided q8-12h PO or IV Adults: 250-750 mg q12h; 200-400 mg IV q12h PO (max dose: 1.5 g/24 hr) |
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; 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 q12h PO Adults: 250-500 mg q12h PO (max dose: 1 g/24 hr) |
Cautions: Adverse events less than erythromycin; GI upset, dyspepsia, nausea, cramping Drug interactions: Same as erythromycin: astemizole carbamazepine, terfenadine, cyclosporine, theophylline, digoxin, tacrolimus |
| 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 gram-positive aerobic and anaerobic cocci except Enterococcus Neonates: Postnatal age ≤7 days weight <2,000 g; 10 mg/kg/24 hr divided q12h IV or IM; weight >2,000 g: 15 mg/kg/24 hr divided q8h IV or IM; >7 days weight <1,200 g: 10 mg/kg/24 hr IV or IM divided q12h; weight 1,200-2,000 g: 15 mg/kg/24 hr divided q8h IV or IM; weight >2,000 g: 20 mg/kg/24 hr divided q8h IV or IM Children: 10-40 mg/kg/24 hr divided q6-8h IV, IM, or PO Adults: 150-600 mg q6-8h IV, IM, or PO (max dose: 5 g/24 hr IV or IM or 2 g/24 hr PO) |
Cautions: Diarrhea, nausea, Clostridium difficile –associated colitis, rash. Administer slow IV over 30-60 min. Topically active as an acne treatment |
| 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: 50-100 mg/kg/24 hr divided q6h PO Adults: 250-500 mg q6h PO (max dose: 4 g/24 hr) |
Cautions: β-Lactam safety profile (rash, eosinophilia). Primarily hepatically eliminated; requires dose reduction in renal disease. Food decreases bioavailability Drug interaction: Probenecid |
| Colistin (Colistimethate sodium; polymyxin E) Injection Inhalation |
Treatment of multidrug resistant gram-negative organisms ( Enterobacteriaceae including extended-spectrum beta lactamase and carbapenemase-producing strains) Children: 2.5-5 mg/kg/day divided in 2-4 divided doses IV Adults: 300 mg/day in 2-4 divided doses IV |
Cautions: Nephrotoxicity (~3% in young children; higher rates in adolescents and adults); adjust dose for renal insufficiency; neurotoxicity (headaches, paresthesia, ataxia) Drug interactions: Should not be administered concomitantly with polymyxins or aminoglycosides |
| Co-trimoxazole (trimethoprim-sulfamethoxazole; TMP-SMX) Bactrim, Cotrim, Septra, Sulfatrim Tablet: SMX 400 mg and TMP 80 mg Tablet DS: SMX 800 mg and TMP 160 mg Suspension: SMX 200 mg and TMP 40 mg/5 mL Injection |
Antibiotic combination with sequential antagonism of bacterial folate synthesis with broad antibacterial activity: Shigella, Legionella, Nocardia, Chlamydia, Pneumocystis jiroveci. Dosage based on TMP component Children: 6-20 mg TMP/kg/24 hr or IV divided q12h PO Pneumocystis carinii pneumonia: 15-20 mg TMP/kg/24 hr divided q12h PO or IV P. carinii prophylaxis: 5 mg TMP/kg/24 hr or 3 times/wk PO Adults: 160 mg TMP q12h PO |
Cautions: Drug dosed on TMP (trimethoprim) component. Sulfonamide skin reactions: rash, erythema multiforme, Stevens-Johnson syndrome, nausea, leukopenia. Renal and hepatic elimination; reduce dose in renal failure Drug interactions: Protein displacement with warfarin, possibly phenytoin, cyclosporine |
| Daptomycin Cubicin |
Disrupts bacterial cell membrane function, causing depolarization leading to inhibition of protein, DNA and RNA synthesis, which results in bacterial cell death. Active against enterococci (including glycopeptide-resistant strains), staphylococci (including MRSA), streptococci, and corynebacteria. Approved for skin and soft tissue infections. Acceptable for bacteremia and right-sided endocarditis with susceptible strains Adults: In skin and soft tissue infections, 4 mg/kg daptomycin IV once daily. For S. aureus bacteremia or right-sided endocarditis, 6 mg/kg IV once daily Children: For skin/skin structure infections, 12-23 mo, 10 mg/kg IV q24h; 2-6 yr, 9 mg/kg IV q24h; 7-11 yr, 7 mg/kg q24h; 12-17 yr, 5 mg/kg q24h, all for up to 14 days. For staphylococcal bacteremia, 1-6 yr, 12 mg/kg q24h; 7-11 yr, 9 mg/kg q24h; 12-17 yr, 7 mg/kg q24h; all for up to 42 days. For staphylococcal endocarditis, 1-5 yr, 10 mg/kg IV q24h for at least 6 wk; ≥6 yr, 6 mg/kg IV q24h for at least 6 wk |
Cautions: Should not be used for pneumonia because drug inactivated by surfactants. Associated with rash, renal failure, anemia, and headache. Is reported to cause myopathy, rhabdomyolysis, and eosinophilic pneumonia Drug interactions: Should not be administered with statins |
| Demeclocycline Declomycin Tablet: 150, 300 mg Capsule: 150 mg |
Tetracycline active against most gram-positive cocci except Enterococcus , many gram-negative bacilli, anaerobes, Borrelia burgdorferi (Lyme disease), Mycoplasma, and Chlamydia Children: 8-12 mg/kg/24 hr divided q6-12h PO Adults: 150 mg PO q6-8h Syndrome of inappropriate antidiuretic hormone secretion: 900-1,200 mg/24 hr or 13-15 mg/kg/24 hr divided q6-8h PO with dose reduction based on response to 600-900 mg/24 hr |
Cautions: Teeth staining, possibly permanent (if administered <8 yr old) 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 |
| Dicloxacillin Dynapen, Pathocil Capsule: 125, 250, 500 mg Suspension: 62.5 mg/5 mL |
Penicillinase-resistant penicillin active against S. aureus and other gram-positive cocci except Enterococcus and coagulase-negative staphylococci Children: 12.5-100 mg/kg/24 hr divided q6h PO Adults: 125-500 mg q6h PO |
Cautions: β-Lactam safety profile (rash, eosinophilia). Primarily renally (65%) and bile (30%) elimination. Food may decrease bioavailability Drug interaction: Probenecid |
| Doripenem Doribax Injection |
Carbapenem antibiotic with broad-spectrum activity against gram-positive cocci and gram-negative bacilli, including P. aeruginosa and anaerobes Children: dose unknown. Adults: 500 mg q8h IV |
Cautions: β-Lactam safety profile; does not undergo hepatic metabolism. Renal elimination (70–75%); dose adjustment for renal failure Drug interactions: Valproic acid, 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, B. burgdorferi (Lyme disease), Mycoplasma , and Chlamydia Children: 2-5 mg/kg/24 hr divided q12-24h PO or IV (max dose: 200 mg/24 hr) Adults: 100-200 mg/24 hr divided q12-24h PO or IV |
Cautions: Teeth staining, possibly permanent (<8 yr old) with prolonged use; photosensitivity, nausea, vomiting, diarrhea, superinfections Drug interactions: Aluminum-, calcium-, magnesium-, zinc-, iron-, kaolin-, and pectin-containing products, food, milk, dairy products may decrease absorption. Carbamazepine, rifampin, and barbiturates may decrease half-life |
| Erythromycin E-Mycin, Ery-Tab, Eryc, Ilosone Estolate 125, 500 mg Tablet EES: 200 mg Tablet base: 250, 333, 500 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 |
Bacteriostatic macrolide antibiotic most active against gram-positive organisms, Corynebacterium diphtheriae , and Mycoplasma pneumoniae Neonates: Postnatal age ≤7 days: 20 mg/kg/24 hr divided q12h PO; >7 days weight <1,200 g: 20 mg/kg/24 hr divided q12h PO; weight >1,200 g: 30 mg/kg/24 hr divided q8h PO (give as 5 mg/kg/dose q6h to improve feeding intolerance) Children: Usual max dose: 2 g/24 hr Base: 30-50 mg/kg/24 hr divided q6-8h PO Estolate: 30-50 mg/kg/24 hr divided q8-12h PO Stearate: 20-40 mg/kg/24 hr divided q6h PO Lactobionate: 20-40 mg/kg/24 hr divided q6-8h IV Gluceptate: 20-50 mg/kg/24 hr divided q6h IV; usual max dose: 4 g/24 hr IV Adults: Base: 333 mg PO q8h; estolate/stearate/base: 250-500 mg q6h PO |
Cautions: Motilin agonist leading to marked abdominal cramping, nausea, vomiting, and diarrhea. Associated with hypertrophic pyloric stenosis in young infants. Many different salts with questionable tempering of GI adverse events. Rare cardiac toxicity with IV use. Dose of salts differ. Topical formulation for treatment of acne Drug interactions: Antagonizes hepatic CYP 3A4 activity: astemizole, carbamazepine, terfenadine, cyclosporine, theophylline, digoxin, tacrolimus, carbamazepine |
| Gentamicin Garamycin Injection Ophthalmic solution, ointment, topical cream |
Aminoglycoside antibiotic active against gram-negative bacilli, especially E. coli, Klebsiella, Proteus, Enterobacter, Serratia, and Pseudomonas Neonates: Postnatal age ≤7 days weight 1,200-2,000 g: 2.5 mg/kg q12-18h IV or IM; weight <2,000 g: 2.5 mg/kg q12h IV or IM; postnatal age >7 days weight 1,200-2,000 g: 2.5 mg/kg q8-12h IV or IM; weight >2,000 g: 2.5 mg/kg q8h IV or IM Children: 2.5 mg/kg/24 hr divided q8-12h IV or IM. Alternatively, may administer 5-7.5 mg/kg/24 hr IV once daily Intrathecal: Preservative-free preparation for intraventricular or intrathecal use: neonate: 1 mg/24 hr; children: 1-2 mg/24 hr intrathecal; adults: 4-8 mg/24 hr Adults: 3-6 mg/kg/24 hr divided q8h IV or IM |
Cautions: Anaerobes, S. pneumoniae, and other Streptococcus are resistant. May cause ototoxicity and nephrotoxicity. Monitor renal function. Drug eliminated renally. Administered IV over 30-60 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 with broad-spectrum activity against gram-positive cocci and gram-negative bacilli, including P. aeruginosa and anaerobes. No activity against Stenotrophomonas maltophilia Neonates: Postnatal age ≤7 days weight <1,200 g: 20 mg/kg q18-24h IV or IM; weight >1,200 g: 40 mg/kg divided q12h IV or IM; postnatal age >7 days weight 1,200-2,000 g: 40 mg/kg q12h IV or IM; weight >2,000 g: 60 mg/kg q8h IV or IM Children: 60-100 mg/kg/24 hr divided q6-8h IV or IM Adults: 2-4 g/24 hr divided q6-8h IV or IM (max dose: 4 g/24 hr) |
Cautions: β-Lactam safety profile (rash, eosinophilia), nausea, seizures. Cilastatin 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 drug-resistant organisms), including Staphylococcus, Streptococcus, E. faecium, and Enterococcus faecalis . Interferes with protein synthesis by binding to 50S ribosome subunit Children: 10 mg/kg q12h IV or PO Adults: Pneumonia: 600 mg q12h IV or PO; skin infections: 400 mg q12h IV or PO |
Adverse events: Myelosuppression, pseudomembranous colitis, nausea, diarrhea, headache Drug interaction: Probenecid |
| Loracarbef Generic Capsule: 200 mg Suspension: 100 mg/5 mL, 200 mg/5 mL |
Carbacephem very closely related to cefaclor (second-generation cephalosporin) active against S. aureus, Streptococcus, H. influenzae, M. catarrhalis, E. coli, Klebsiella , and Proteus Children: 30 mg/kg/24 hr divided q12h PO (max dose: 2 g) Adults: 200-400 mg q12h PO (max dose: 800 mg/24 hr) |
Cautions: β-Lactam safety profile (rash, eosinophilia). Renally eliminated Drug interaction: Probenecid |
| Meropenem Merrem Injection |
Carbapenem antibiotic with broad-spectrum activity against gram-positive cocci and gram-negative bacilli, including P. aeruginosa and anaerobes. No activity against S. maltophilia Children: 60 mg/kg/24 hr divided q8h IV meningitis: 120 mg/kg/24 hr (max dose: 6 g/24 hr) q8h IV Adults: 1.5-3 g q8h IV |
Cautions: β-Lactam safety profile; appears to possess less CNS excitation than imipenem. 80% renal elimination Drug interaction: Probenecid |
| Metronidazole Flagyl, Metro I.V., Topical gel, vaginal gel Injection Tablet: 250, 500 mg |
Highly effective in the treatment of infections caused by anaerobes. Oral therapy of C. difficile colitis Neonates: weight <1,200 g: 7.5 mg/kg/48 hr PO or IV; postnatal age ≤7 days weight 1,200-2,000 g: 7.5 mg/kg/24 hr q24h PO or IV; weight 2,000 g: 15 mg/kg/24 hr divided q12h PO or IV; postnatal age <7 days weight 1,200-2,000 g: 15 mg/kg/24 hr divided q12h PO or IV; weight >2,000 g: 30 mg/kg/24 hr divided q12 h PO or IV Children: 30 mg/kg/24 hr divided q6-8h PO or IV Adults: 30 mg/kg/24 hr divided q6h PO or IV (max dose: 4 g/24 hr) |
Cautions: Dizziness, seizures, metallic taste, nausea, disulfiram-like reaction with alcohol. Administer IV slow over 30-60 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 ≤7 days: 150 mg/kg/24 hr divided q12h IV; >7 days: 225 mg/kg divided q8h IV Children: 200-300 mg/kg/24 hr divided q4-6h IV; cystic fibrosis 300-450 mg/kg/24 hr IV Adults: 2-4 g/dose q4-6h IV (max dose: 12 g/24 hr) |
Cautions: β-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 liver function test results. Renally eliminated. Inactivated by β-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 2-4 times daily |
Caution: Minimal systemic absorption because 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 weight 1,200-2,000 g: 50 mg/kg/24 hr divided q12h IV or IM; weight >2,000 g: 75 mg/kg/24 hr divided q8h IV or IM; postnatal age >7 days weight 1,200-2,000 g: 75 mg/kg/24 hr divided q8h; weight >2,000 g: 100 mg/kg/24 hr divided q6-8h IV (meningitis: 200 mg/kg/24 hr divided q6h IV) Children: 100-200 mg/kg/24 hr divided q4-6h IV Adults: 4-12 g/24 hr divided q4-6h IV (max dose: 12 g/24 hr) |
Cautions: β-Lactam safety profile (rash, eosinophilia), phlebitis; painful given intramuscularly; oral absorption highly variable and erratic (not recommended) Adverse effect: Neutropenia |
| Nalidixic acid NegGram Tablet: 250, 500, 1,000 mg Suspension: 250 mg/5 mL |
First-generation quinolone effective for short-term treatment of lower UTIs caused by E. coli, Enterobacter, Klebsiella , and Proteus Children: 50-55 mg/kg/24 hr divided q6h PO; suppressive therapy: 25-33 mg/kg/24 hr divided q6-8h PO Adults: 1 g q6h PO; suppressive therapy: 500 mg q6h PO |
Cautions: Vertigo, dizziness, rash. Not for use in systemic infections Drug interactions: Liquid antacids |
| Neomycin sulfate Mycifradin Tablet: 500 mg Topical cream, ointment Solution: 125 mg/5 mL |
Aminoglycoside antibiotic used for topical application or orally before surgery to decrease GI flora (nonabsorbable) and hyperammonemia Infants: 50 mg/kg/24 hr divided q6h PO Children: 50-100 mg/kg/24 hr divided q6-8h PO Adults: 500-2,000 mg/dose q6-8h 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 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 treatment of lower UTIs caused by gram-positive and gram-negative pathogens Children: 5-7 mg/kg/24 hr divided q6h PO (max dose: 400 mg/24 hr); suppressive therapy 1-2.5 mg/kg/24 hr divided q12-24h PO (max dose: 100 mg/24 hr) Adults: 50-100 mg/24 hr divided q6h 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 or chronic suppurative otitis media (otic solution) caused by susceptible gram-positive, gram-negative, anaerobic bacteria, or C. trachomatis Child >1-12 yr: Conjunctivitis: 1-2 drops in affected eye(s) q2-4h for 2 days, then 1-2 drops qid for 5 days Corneal ulcers: 1-2 drops q 30 min while awake and at 4 hr intervals at night for 2 days, then 1-2 drops hourly for 5 days while awake, then 1-2 drops q6h 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 |
Adverse events: Burning, stinging, eye redness (ophthalmic solution), dizziness with otic solution if not warmed |
| 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 ≤7 days weight 1,200-2,000 g: 50 mg/kg/24 hr divided q12h IV; weight >2,000 g: 75 mg/kg/24 hr IV divided q8h IV; postnatal age >7 days weight <1,200 g: 50 mg/kg/24 hr IV divided q12h IV; weight 1,200-2,000 g: 75 mg/kg/24 hr divided q8h IV; weight >2,000 g: 100 mg/kg/24 hr IV divided q6h IV Infants: 100-200 mg/kg/24 hr divided q4-6h IV Children: PO 50-100 mg/kg/24 hr divided q4-6h IV Adults: 2-12 g/24 hr divided q4-6h IV (max dose: 12 g/24 hr) |
Cautions: β-Lactam safety profile (rash, eosinophilia) Moderate oral bioavailability (35–65%) Primarily renally eliminated Drug interaction: Probenecid Adverse effect: Neutropenia |
| Penicillin G Injection Tablets |
Penicillin active against most gram-positive 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 weight 1,200-2,000 g: 50,000 units/kg/24 hr divided q12h IV or IM (meningitis: 100,000 U/kg/24 hr divided q12h IV or IM); weight >2,000 g: 75,000 U/kg/24 hr divided q8h IV or IM (meningitis: 150,000 U/kg/24 hr divided q8h IV or IM); postnatal age >7 days weight ≤1,200 g: 50,000 U/kg/24 hr divided q12h IV (meningitis: 100,000 U/kg/24 hr divided q12h IV); weight 1,200-2,000 g: 75,000 U/kg/24 hr q8h IV (meningitis: 225,000 U/kg/24 hr divided q8h IV); weight >2,000 g: 100,000 U/kg/24 hr divided q6h IV (meningitis: 200,000 U/kg/24 hr divided q6h IV) Children: 100,000-250,000 units/kg/24 hr divided q4-6h IV or IM (max dose: 400,000 U/kg/24 hr) Adults: 2-24 million units/24 hr divided q4-6h IV or IM |
Cautions: β-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 |
| Penicillin G, benzathine Bicillin Injection |
Long-acting repository form of penicillin effective in treatment of infections responsive to persistent, low penicillin concentrations (1-4 wk), e.g., group A streptococcus pharyngitis, rheumatic fever prophylaxis Neonates weight >1,200 g: 50,000 units/kg IM once Children: 300,000-1.2 million units/kg q 3-4 wk IM (max dose: 1.2-2.4 million units/dose) Adults: 1.2 million units IM q 3-4 wk |
Cautions: β-Lactam safety profile (rash, eosinophilia), allergy. Administer by IM injection only. Substantial pathogen resistance. Primarily renally eliminated Drug interaction: Probenecid |
| Penicillin G, procaine Crysticillin Injection |
Repository form of penicillin providing low penicillin concentrations for 12 hr Neonates weight >1,200 g: 50,000 units/kg/24 hr IM Children: 25,000-50,000 units/kg/24 hr IM for 10 days (max dose: 4.8 million units/dose) Gonorrhea: 100,000 units/kg (max dose: 4.8 million units/24 hr) IM once with probenecid 25 mg/kg (max dose: 1 g) Adults: 0.6-4.8 million units q12-24h IM |
Cautions: β-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 Tablet: 125, 250, 500 mg Suspension: 125 mg/5 mL, 250 mg/5 mL |
Preferred oral dosing form of penicillin, active against most gram-positive cocci; S. pneumoniae (resistance is increasing), other streptococci, and some gram-negative bacteria (e.g., N. gonorrhoeae, N. meningitidis ) Children: 25-50 mg/kg/24 hr divided q4-8h PO Adults: 125-500 mg q6-8h PO (max dose: 3 g/24 hr) |
Cautions: β-Lactam safety profile (rash, eosinophilia), allergy, 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 q8-12h IV; >7 days; 200 mg/kg divided q6-8h IV Children: 200-300 mg/kg/24 hr divided q4-6h IV; cystic fibrosis: 350-500 mg/kg/24 hr IV Adults: 2-4 g/dose q4-6h (max dose: 24 g/24 hr) IV |
Cautions: β-Lactam safety profile (rash, eosinophilia); painful given intramuscularly; each gram contains 1.9 mEq sodium. Interferes with platelet aggregation/serum sickness–like reaction with high doses; increases in liver function test results. Renally eliminated. Inactivated by penicillinase Drug interaction: Probenecid |
| Piperacillin-tazobactam Zosyn Injection |
Extended-spectrum penicillin (piperacillin) combined with a β -lactamase inhibitor (tazobactam) active against S. aureus, H. influenzae, E. coli, Enterobacter, Serratia, Acinetobacter, P. aeruginosa, and Bacteroides Children: 300-400 mg/kg/24 hr divided q6-8h IV or IM Adults: 3.375 g q6-8h IV or IM |
Cautions: β-Lactam safety profile (rash, eosinophilia); painful given intramuscularly; each gram contains 1.9 mEq sodium Interferes with platelet aggregation, serum sickness–like 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 vancomycin-resistant E. faecium (VRE) and methicillin-resistant S. aureus (MRSA). Not active against E. faecalis Children and adults: VRE: 7.5 mg/kg q8h IV for VRE; skin infections: 7.5 mg/kg q12h IV |
Adverse events: Pain, edema, or phlebitis at injection site, nausea, diarrhea Drug interactions : Synercid is a potent inhibitor of CYP 3A4 |
| Sulfadiazine Tablet: 500 mg |
Sulfonamide antibiotic primarily indicated for treatment of lower UTIs caused by E. coli, P. mirabilis, and Klebsiella Toxoplasmosis: Neonates: 100 mg/kg/24 hr divided q12h PO with pyrimethamine 1 mg/kg/24 hr PO (with folinic acid) Children: 120-200 mg/kg/24 hr divided q6h PO with pyrimethamine 2 mg/kg/24 hr divided q12h PO ≥3 days, then 1 mg/kg/24 hr (max dose: 25 mg/24 hr) with folinic acid Rheumatic fever prophylaxis: weight ≤30 kg: 500 mg/24 hr q24h PO; weight >30 kg: 1 g/24 hr q24h PO |
Cautions: Rash, Stevens-Johnson 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 |
| Sulfamethoxazole Gantanol Tablet: 500 mg Suspension: 500 mg/5 mL |
Sulfonamide antibiotic used for treatment of otitis media, chronic bronchitis, and lower UTIs caused by susceptible bacteria Children: 50-60 mg/kg/24 hr divided q12h PO Adults: 1 g/dose q12h PO (max dose: 3 g/24 hr) |
Cautions: Rash, Stevens-Johnson 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 Ophthalmic solution, ointment |
Sulfonamide antibiotic used for treatment of otitis media, chronic bronchitis, and lower UTIs caused by susceptible bacteria Children: 120-150 mg/kg/24 hr divided q4-6h PO (max dose: 6 g/24 hr) Adults: 4-8 g/24 hr divided q4-6h PO |
Cautions: Rash, Stevens-Johnson syndrome, nausea, leukopenia, crystalluria. Renal and hepatic elimination; avoid use with renal disease. Half-life: ~7-12 hr. Initial dose often a loading dose (doubled) Drug interactions: Protein displacement with warfarin, phenytoin, methotrexate |
| Tigecycline Tygacil Injection |
Tetracycline-class antibiotic (glycylcycline) active against Enterobacteriaceae, including extended spectrum β -lactamase producers; streptococci (including VRE); staphylococci (including MRSA); and anaerobes Children: unknown Adults: 100 mg loading dose followed by 50 mg q12h IV |
Cautions: Pregnancy; children <8 yr old; photosensitivity; hypersensitivity to tetracyclines; hepatic impairment (~60% hepatic clearance) Drug interaction: Warfarin; mycophenolate mofetil |
| 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, weight 1,200-2,000 g: 2.5 mg/kg q12-18h IV or IM; weight >2,000 g: 2.5 mg/kg q12h IV or IM; postnatal age >7 days, weight 1,200-2,000 g: 2.5 mg/kg q8-12h IV or IM; weight >2,000 g: 2.5 mg/kg q8h IV or IM Children: 2.5 mg/kg/24 hr divided q8-12h IV or IM. Alternatively, may administer 5-7.5 mg/kg/24 hr IV. Preservative-free preparation for intraventricular or intrathecal use: neonate, 1 mg/24 hr; children, 1-2 mg/24 hr; adults, 4-8 mg/24 hr Adults: 3-6 mg/kg/24 hr divided q8h IV or IM |
Cautions: S. pneumoniae , other Streptococcus, and anaerobes are resistant. May cause ototoxicity and nephrotoxicity. Monitor renal function. Drug eliminated renally. Administered IV over 30-60 min Drug interactions: May potentiate other ototoxic and nephrotoxic drugs Target serum concentrations: Peak 6-12 mg/L; trough <2 mg/L |
| Trimethoprim Proloprim, Trimpex Tablet: 100, 200 mg |
Folic acid antagonist effective in prophylaxis and treatment of E. coli, Klebsiella, P. mirabilis, and Enterobacter UTIs; P. carinii pneumonia Children: For UTI: 4-6 mg/kg/24 hr divided q12h PO Children >12 yr and adults: 100-200 mg q12h PO. P. carinii pneumonia (with dapsone): 15-20 mg/kg/24 hr divided q6h for 21 days PO |
Cautions: Megaloblastic anemia, bone marrow suppression, nausea, epigastric distress, rash Drug interactions: Possible interactions with phenytoin, cyclosporine, rifampin, warfarin |
| Vancomycin Vancocin, Lyphocin Injection Capsule: 125 mg, 250 mg Suspension |
Glycopeptide antibiotic active against most gram-positive pathogens including staphylococci (including MRSA and coagulase-negative staphylococci), S. pneumoniae including penicillin-resistant strains, Enterococcus (resistance is increasing), and C. difficile –associated colitis Neonates: Postnatal age ≤7 days, weight <1,200 g: 15 mg/kg/24 hr divided q24h IV; weight 1,200-2,000 g: 15 mg/kg/24 hr divided q12-18h IV; weight >2,000 g: 30 mg/kg/24 hr divided q12h IV; postnatal age >7 days, weight <1,200 g: 15 mg/kg/24 hr divided q24h IV; weight 1,200-2,000 g: 15 mg/kg/24 hr divided q8-12h IV; weight >2,000 g: 45 mg/kg/24 hr divided q8h IV Children: 45-60 mg/kg/24 hr divided q8-12h IV; C. difficile –associated colitis; 40-50 mg/kg/24 hr divided q6-8h PO |
Cautions: Ototoxicity and nephrotoxicity particularly when co-administered with other ototoxic and nephrotoxic drugs Infuse IV over 45-60 min. Flushing (red man syndrome) associated with rapid IV infusions, fever, chills, phlebitis (central line is preferred). Renally eliminated. Target serum concentrations: Peak (1 hr after 1 hr infusion) 30-40 mg/L; trough 5-10 mg/L |
CNS, Central nervous system; GI, gastrointestinal; IM, intramuscular/ly; IV, intravenous/ly; PO, oral/ly; q12-24h, every 12 to 24 hours; bid, twice daily; qid, 4 times daily; UTIs, urinary tract infections.
* In the Drug column, the generic drug name is in bold . In the Indications column, bold indicates major organisms targeted and mechanisms of action.
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