AHFS Class:

• Aminoglycosides 8:12.02

Generic Name(s):

• Gentamicin Sulfate

Associated Monographs

• Aminoglycosides General Statement

Gentamicin is an aminoglycoside antibiotic.1,2,3,4,5,10

Serious Bacterial Infections

Gentamicin is used for the treatment of serious bone and joint infections, respiratory tract infections, septicemia, skin and skin structure infections, and urinary tract infections caused by susceptible gram-negative bacteria, including Citrobacter , Enterobacter , Escherichia coli , Klebsiella , Proteus , Serratia , or Pseudomonas aeruginosa .1,2,3,4,5,6,7,10,66,75,77 The drug usually is used as an adjunct to an appropriate β-lactam (e.g., ceftriaxone, cefotaxime, cefepime, piperacillin and tazobactam, ticarcillin and clavulanate) or carbapenem (e.g., imipenem, meropenem) for empiric treatment of these infections6,7,66,75 . Gentamicin is not usually indicated for initial treatment of uncomplicated infections (e.g., uncomplicated urinary tract infections) unless the causative organism is susceptible and other less toxic anti-infectives cannot be used.1,2,3,4

Gentamicin has been used for the treatment of serious infections, including bone and joint infections, septicemia, skin and skin structure infections, and urinary tract infections caused by susceptible Staphylococcus aureus .1,2,3,4 Although gentamicin and other aminoglycosides are not usually recommended for the treatment of staphylococcal infections, the manufacturers state that gentamicin may be considered for the treatment of known or suspected staphylococcal infections in certain situations.1,2,3,4 This includes treatment of infections caused by susceptible staphylococci when other more appropriate anti-infectives are contraindicated (e.g., because of hypersensitivity) or would be ineffective because of resistance and for initial treatment of mixed infections when the causative organisms may be either gram-negative bacteria or staphylococci.1,2,3,4,6 A regimen of vancomycin with or without gentamicin and with or without rifampin has been recommended for the treatment of oxacillin-resistant (methicillin-resistant) staphylococcal infections.6

Intra-abdominal Infections

Gentamicin is used for the treatment of serious intra-abdominal infections (including peritonitis) caused by susceptible Citrobacter , Enterobacter , E. coli , Klebsiella , Proteus , Serratia , Pseudomonas aeruginosa , or S. aureus .1,2,3,4,5,6,7,10,77 Gentamicin usually is used as an adjunct to other appropriate anti-infectives (e.g., clindamycin, metronidazole, piperacillin and tazobactam, ampicillin and sulbactam).6,77

The Infectious Diseases Society of America (IDSA) states that patients with community-acquired intra-abdominal infections of mild to moderate severity may receive initial treatment with an empiric regimen of the fixed combination of ampicillin and sulbactam, cefazolin or cefuroxime in conjunction with metronidazole, the fixed combination of ticarcillin and clavulanate, ertapenem monotherapy, or a fluoroquinolone (ciprofloxacin, levofloxacin, moxifloxacin) in conjunction with metronidazole.77 Patients who are immunosuppressed or have more severe community-acquired intra-abdominal infections should receive a regimen that has a broader spectrum of activity such as meropenem monotherapy; imipenem and cilastatin monotherapy; a third or fourth generation cephalosporin (cefotaxime, ceftriaxone, ceftazidime, cefepime) in conjunction with metronidazole; ciprofloxacin in conjunction with metronidazole; the fixed combination of piperacillin and tazobactam; or aztreonam in conjunction with metronidazole.77

The IDSA states that aminoglycosides are not recommended for routine use in community-acquired intra-abdominal infections; however, an aminoglycoside may be included in empiric regimens for the treatment of nosocomial intra-abdominal infections, depending on local patterns of in vitro susceptibility of nosocomial isolates.77 IDSA states that aminoglycosides generally should be reserved for when β-lactams and fluoroquinolones cannot be used.77 Other clinicians suggest that severely ill patients and those with prolonged hospitalization should receive an initial regimen that includes an antipseudomonal agent such as an antipseudomonal penicillin (ticarcillin and clavulanate, piperacillin and tazobactam), a carbapenem (imipenem or meropenem), ceftazidime, or cefepime used in conjunction with metronidazole.6 These clinicians state that an aminoglycoside also could be included in the empiric regimen.6

Endocarditis

Gentamicin is used for the treatment of bacterial endocarditis†7,19,49 and for prevention of bacterial endocarditis†.7,202

Treatment

Enterococcal Endocarditis

Gentamicin is used in conjunction with an appropriate anti-infective (ampicillin, penicillin G sodium, vancomycin) for the treatment of native or prosthetic valve endocarditis† caused by Enterococcus (e.g., E. faecalis , E. faecium ).19 Enterococci usually are resistant to aminoglycosides alone and also are relatively resistant to ampicillin, penicillin G and vancomycin.19,92 However, because antibacterial activity of the drugs may be additive or synergistic, regimens of gentamicin or streptomycin used concomitantly with ampicillin, penicillin G sodium, or vancomycin may be effective in the treatment of enterococcal endocarditis.19,92,93

For the treatment of native or prosthetic valve enterococcal endocarditis caused by strains susceptible to penicillin, vancomycin, and aminoglycosides, the American Heart Association (AHA) and IDSA recommend a regimen of IV ampicillin sodium or IV penicillin G sodium given in conjunction with either IV or IM gentamicin or IV or IM streptomycin.19 Streptomycin usually is used only if the strains are gentamicin-resistant.19 For patients unable to tolerate penicillins, an alternative regimen is IV vancomycin given in conjunction with IV or IM gentamicin or IV or IM streptomycin.19

Enterococcal isolates should routinely be tested for in vitro susceptibility to penicillin and vancomycin and for high-level resistance to gentamicin and streptomycin.19,49 (See Spectrum: In Vitro Susceptibility Testing in the Aminoglycosides General Statement 8:12.02.) The most appropriate regimen for the treatment of enterococcal endocarditis is selected based on results of in vitro susceptibility testing; treatment duration depends on whether native or prosthetic valves are involved and how long symptoms have been present prior to initiation of treatment.19 Gentamicin usually is the preferred aminoglycoside for the treatment of enterococcal endocarditis,10,19,93,94,95 in part because IV gentamicin may be better tolerated than IM streptomycin and because laboratory monitoring of serum gentamicin concentrations may be more readily available than laboratory monitoring of streptomycin concentrations.19,95 However, streptomycin may be effective for the treatment of enterococcal endocarditis caused by gentamicin-resistant strains since some, but not all, enterococci with high-level resistance to gentamicin are susceptible to streptomycin.5,10,19,92,93,94 Vancomycin should be used only in patients unable to tolerate ampicillin or penicillin G since regimens that include vancomycin and an aminoglycoside may be associated with an increased risk of ototoxicity and nephrotoxicity and may be less effective compared with regimens that include one of the β-lactams and an aminoglycoside.19 (See Drug Interactions: Neurotoxic, Ototoxic, or Nephrotoxic Drugs, in the Aminoglycosides General Statement 8:12.02.)

Endocarditis Caused by Viridans Streptococci or S. bovis

Gentamicin is used in conjunction with other appropriate anti-infectives for the treatment of endocarditis caused by viridans streptococci† (e.g., S. sanguis , S. oralis , S. salivarius , S. mutans , Gamella morbillorum ) or S. bovis † (nonenterococcal group D streptococci).19,49

For the treatment of native valve endocarditis caused by viridans streptococci or S. bovis highly susceptible to penicillin (i.e., penicillin MIC of 0.12 mcg/mL or less), the AHA and IDSA recommend monotherapy with IV penicillin G sodium or IV or IM ceftriaxone given for 4 weeks.19 These monotherapy regimens avoid the use of gentamicin and are preferred in most patients older than 65 years of age and in those with impaired renal or eighth cranial nerve function.19 In selected patients only, the AHA and IDSA state that a 2-week regimen that consists of IV penicillin G sodium or IV or IM ceftriaxone in conjunction with IV or IM gentamicin can be used.19 The 2-week regimen should be used only in patients with uncomplicated native valve endocarditis caused by highly penicillin-susceptible viridans streptococci or S. bovis who are at low risk for gentamicin adverse effects; the 2-week regimen should not be used in those with known cardiac or extracardiac abscess, creatinine clearance less than 20 mL/minute, impaired eighth cranial nerve function, or infections caused by Abiotrophia , Granulicatella , or Gemella .19

For the treatment of native valve endocarditis caused by viridans streptococci or S. bovis relatively resistant to penicillin (i.e., penicillin MIC greater than 0.12 mcg/mL and less than or equal to 0.5 mcg/mL), the AHA and IDSA recommend a 4-week regimen of IV penicillin G sodium or IV or IM ceftriaxone in conjunction with IV or IM gentamicin given during the initial 2 weeks of treatment.19 Alternatively, in patients unable to tolerate penicillin G sodium or ceftriaxone, IV vancomycin can be used.19

In patients with prosthetic valves or other prosthetic material who have endocarditis caused by viridans streptococci or S. bovis highly susceptible to penicillin (i.e., penicillin MIC of 0.12 mcg/mL or less), the AHA and IDSA recommend a 6-week regimen of IV penicillin G sodium or IV or IM ceftriaxone with or without IV or IM gentamicin given during the initial 2 weeks of treatment.19 When highly penicillin-susceptible strains are involved, it is unclear whether the combination regimen that includes an aminoglycoside during the first 2 weeks is more effective than use of the β-lactam alone.19 If the strains involved are relatively or fully penicillin-resistant (i.e., penicillin MIC greater than 0.12 mcg/mL), the AHA and IDSA recommend a 6-week regimen of IV penicillin G sodium or IV or IM ceftriaxone given with a 6-week regimen of IV or IM gentamicin.19 Alternatively, in patients unable to tolerate penicillin G sodium or ceftriaxone, a 6-week regimen of IV vancomycin can be used.19

Endocarditis caused by viridans streptococci or S. bovis highly resistant to penicillin (i.e., penicillin MIC greater than 0.5 mcg/mL) or caused by Abiotrophia defectiva , Granulicatella , or Gamella should be treated with a regimen recommended for enterococcal endocarditis.19 (See Enterococcal Endocarditis under Uses: Endocarditis.)

Staphylococcal Endocarditis

Gentamicin is used in conjunction with other appropriate anti-infectives for the treatment of staphylococcal endocarditis†, including infections caused by coagulase-positive strains ( S. aureus ) or coagulase-negative strains (e.g., S. epidermidis , S. lugdunensis ).19,49

For the treatment of native valve endocarditis caused by oxacillin-susceptible staphylococci, the AHA and IDSA recommend a regimen of IV nafcillin or oxacillin with or without IV or IM gentamicin.19 For penicillin-allergic patients (nonanaphylactoid type only), a regimen of IV cefazolin with or without IV or IM gentamicin is recommended.19 In patients with complicated right-sided staphylococcal endocarditis or with left-sided staphylococcal endocarditis, a 6-week regimen of the β-lactam should be used and gentamicin given concomitantly during the first 3-5 days of treatment.19 In those with uncomplicated right-sided staphylococcal endocarditis (i.e., patients with no evidence of renal failure, extrapulmonary metastatic infections, aortic or mitral valve involvement, meningitis, or oxacillin-resistant strains), a 2-week regimen that includes both the β-lactam and gentamicin can be considered.19

Staphylococcal endocarditis in patients with prosthetic valves or other prosthetic material usually is caused by oxacillin-resistant staphylococci, especially when endocarditis develops within 1 year after surgery, and is associated with high morbidity and mortality rates.19 Unless susceptibility to oxacillin has been demonstrated using in vitro susceptibility testing, it should be assumed that patients with staphylococcal prosthetic valve endocarditis have oxacillin-resistant strains.19 If prosthetic valve endocarditis is known to be caused by oxacillin-susceptible staphylococci, the AHA and IDSA recommend at least 6 weeks of IV nafcillin or oxacillin in conjunction with IV or oral rifampin and concomitant use of IV or IM gentamicin during the initial 2 weeks of treatment.19 If the strain is known to be penicillin susceptible (i.e., penicillin MIC of 0.1 mcg/mL or less) and does not produce β-lactamase, IV penicillin G sodium can be substituted for nafcillin or oxacillin in this regimen; for penicillin-allergic patients (nonanaphylactoid type only), IV cefazolin can be substituted for nafcillin or oxacillin.19 If the strain is known or presumed to be oxacillin-resistant, the AHA and IDSA recommend at least 6 weeks of IV vancomycin in conjunction with IV or oral rifampin and concomitant use of IV or IM gentamicin during the initial 2 weeks of treatment.19

Prevention

Gentamicin is used in conjunction with ampicillin or with vancomycin (in penicillin-allergic patients) for prevention of bacterial endocarditis† in patients undergoing certain genitourinary and GI tract (except esophageal) surgery or instrumentation who have cardiac conditions that put them at high risk.7,202 (See Prophylaxis of Bacterial Endocarditis under Uses: Prophylaxis in the Aminopenicillins General Statement 8:12.16.08.)

The current recommendations published by the AHA should be consulted for specific information on which cardiac conditions are associated with high or moderate risk of endocarditis and which procedures require prophylaxis.202

Meningitis and Other CNS Infections

Gentamicin is used in conjunction with other anti-infectives for the treatment of CNS infections (meningitis) caused by susceptible S. aureus , Citrobacter , Enterobacter , E. coli , Klebsiella , Proteus , Serratia , or Ps. aeruginosa .1,2,3,4,6,7,67,69,74 Like other aminoglycosides, gentamicin should not be used alone for the treatment of meningitis, but may be used as an adjunct to other appropriate anti-infectives.6,67

For initial empiric treatment of neonatal meningitis, especially when Streptococcus agalactiae (group B streptococci), E. coli , or Listeria monocytogenes might be involved, a regimen of ampicillin and cefotaxime with or without gentamicin has been recommended.6,7,67,74 For the treatment of nosocomial meningitis when Pseudomonas are involved, a regimen of vancomycin, an antipseudomonal cephalosporin (e.g., ceftazidime), and an aminoglycoside (amikacin, gentamicin, tobramycin) has been recommended.6 For the treatment of enterococcal meningitis†, a regimen of ampicillin and gentamicin has been recommended; if ampicillin-resistant enterococci are involved, a regimen of vancomycin and gentamicin has been recommended.67

To provide higher gentamicin CSF concentrations for the treatment of meningitis, gentamicin has been given intrathecally† or intraventricularly† concomitantly with IM or IV administration.5,18,67 Although concomitant parenteral and intrathecal or intraventricular therapy may result in higher anti-infective CSF concentrations, such therapy also may be associated with increased mortality in neonates.5,73 Some clinicians state that intraventricular gentamicin should not be used routinely for the treatment of meningitis and should be reserved for patients who do not respond or are not likely to respond to parenteral anti-infectives alone.5

Bartonella Infections

Gentamicin has been used in the treatment of Bartonella infections†, including infections caused by B. henselae (e.g., cat scratch disease, bacillary angiomatosis, bacillary peliosis hepatitis, endocarditis), B. quintana (e.g., bacteremia, endocarditis, trench fever, bacillary angiomatosis), or B. bacilliformis (Carrion's disease).6,7,78,79,80,81

Optimum anti-infective regimens for the treatment of Bartonella infections have not been identified, and various drugs have been used to treat these infections, including aminoglycosides (gentamicin), tetracyclines (doxycycline), macrolides (erythromycin, azithromycin), cephalosporins (ceftriaxone), quinolones (ciprofloxacin), chloramphenicol, vancomycin, co-trimoxazole, or rifampin.6,7,78,79,80,81,82,83,85,86 There is some evidence that effective treatment of Bartonella endocarditis should include an aminoglycoside (gentamicin) during at least the first 2 weeks of therapy.7,79

Although cat scratch disease caused by B. henselae generally is a self-limited illness in immunocompetent individuals and localized infections may resolve spontaneously in 2-4 months, anti-infective therapy should be considered for acutely or severely ill patients with systemic manifestations, especially those with hepatic or splenic involvement, endocarditis, extensive lymphadenopathy, painful adenitis, or compromised immune function.7,78,82 Anti-infectives are indicated in patients with B. quintana infections and those who develop bacillary angiomatosis, bacillary peliosis, or trench fever.7,78,81,82 B. quintana infections have been reported most frequently in immunocompromised patients (e.g., individuals with HIV infection), homeless individuals in urban areas, and chronic alcohol abusers.78,81,83,84,86 Bartonella infections tend to persist or recur and prolonged therapy (several months or longer) usually is necessary, especially in immunocompromised patients.7,78,83,86

Brucellosis

Treatment

Gentamicin is used in the treatment of brucellosis†.6,7,47,48,258 Tetracyclines generally are considered the drugs of choice for the treatment of brucellosis; however, concomitant use of another anti-infective (e.g., streptomycin or gentamicin and/or rifampin) is recommended to reduce the likelihood of relapse, especially for severe infections and when there are complications such as meningitis, endocarditis, or osteomyelitis.7,46,48,258 Monotherapy is no longer recommended for the treatment of brucellosis since such therapy is associated with high relapse rates.7,48,258

A regimen of oral doxycycline and oral rifampin may be effective for the treatment of less severe brucellosis.7,258 For the treatment of acute, complicated brucellosis (e.g., skeletal disease, endocarditis), a regimen of oral doxycycline (or oral co-trimoxazole in children younger than 8 years of age) and oral rifampin, with IM streptomycin given during the first 2-3 weeks usually is recommended.7,47,258 Gentamicin can be used if streptomycin is unavailable.258 Although data are limited, alternative regimens that have been suggested for the treatment of brucellosis include co-trimoxazole with or without gentamicin (or streptomycin) or rifampin; ciprofloxacin (or ofloxacin) and rifampin; and chloramphenicol with or without streptomycin.6,7,48,258 For the treatment of neurobrucellosis, a regimen that includes a tetracycline, rifampin, and streptomycin is recommended.45

Prophylaxis

Postexposure prophylaxis with anti-infectives is not generally recommended after possible exposure to endemic brucellosis; however, use of an anti-infective regimen recommended for the treatment of brucellosis (e.g., doxycycline and rifampin) should be considered following a high-risk exposure to Brucella .7,258 These high-risk exposures include needlestick injuries involving the brucella vaccine available for veterinary use (a brucella vaccine for use in humans is not available), inadvertent laboratory exposure to the organism, or confirmed exposure in the context of biologic warfare or bioterrorism.258

Granuloma Inguinale (Donovanosis)

Gentamicin is used as an adjunct in the treatment of granuloma inguinale† (donovanosis), a sexually transmitted disease caused by Klebsiella granulomatis (formerly Calymmatobacterium granulomatis ) involving genital ulcerative lesions.7,201 The CDC recommends that donovanosis be treated with a regimen of oral doxycycline or, alternatively, a regimen of oral azithromycin, oral ciprofloxacin, oral erythromycin, or oral co-trimoxazole.201 If lesions do not respond within the first few days of therapy, the CDC recommends that an aminoglycoside (e.g., gentamicin) be added to the treatment regimen.201 The CDC also states that consideration should be given to adding an aminoglycoside (e.g., gentamicin) to the treatment regimen in pregnant and lactating women and in HIV-infected individuals.201

Pelvic Inflammatory Disease

The CDC and many clinicians currently suggest IV clindamycin in conjunction with IV or IM gentamicin as one of several possible parenteral regimens for the treatment of acute pelvic inflammatory disease† (PID) in adults and adolescents.89,201,212

For additional information on treatment of PID, see Uses: PID in Ceftriaxone Sodium 8:12.06.12.

Plague

Treatment

Gentamicin is used for the treatment of plague† caused by Yersinia pestis .6,7,50,90,91,99,256,258 Streptomycin generally has been considered the drug of choice for the treatment of bubonic, septicemia, and pneumonic plague;6,7,50,99,256,258 however, gentamicin also is considered a drug of choice since it may be as effective and is more readily available than streptomycin.7,50,90,91,99,256,258 Alternatives recommended when aminoglycosides are not used include doxycycline (or tetracycline), chloramphenicol, co-trimoxazole (may be less effective than other alternatives), or fluoroquinolones (ciprofloxacin, ofloxacin).6,7,50,99,256,258 Chloramphenicol generally is considered the drug of choice for the treatment of plague meningitis.7,50,99,258 Penicillins and other β-lactams are not recommended for the treatment of plague.99

Anti-infective regimens recommended for the treatment of naturally occurring or endemic bubonic, septicemic, or pneumonic plague also are recommended for the treatment of plague that occurs following exposure to Y. pestis in the context of biologic warfare or bioterrorism.50,256 These exposures would most likely result in primary pneumonic plague.256 Prompt initiation of anti-infective therapy (within 18-24 hours of onset of symptoms) is essential in the treatment of pneumonic plague.256,258 Some experts (e.g., the US Working Group on Civilian Biodefense, US Army Medical Research Institute of Infectious Diseases [USAMRIID], European Commission Task Force on Biological and Chemical Agent Threats [BICHAT]) recommend that treatment of plague in the context of biologic warfare or bioterrorism should be initiated with a parenteral anti-infective such as streptomycin (or gentamicin) or, alternatively, doxycycline, ciprofloxacin, or chloramphenicol; an oral regimen (doxycycline, ciprofloxacin) may be substituted when the patient's condition improves or if parenteral therapy is unavailable.50,256,258

Prompt initiation of anti-infective therapy (within 18-24 hours of onset of symptoms) is essential in the treatment of pneumonic plague.256,258 When plague is suspected, appropriate anti-infectives should be initiated immediately and not delayed for laboratory confirmation.91

Prophylaxis

Postexposure prophylaxis with anti-infectives is recommended after high-risk exposures to plague, including close exposure to individuals with naturally occurring plague or laboratory exposure to viable Y. pestis .7,96,258 In the context of biologic warfare or bioterrorism, some experts (e.g., the US Working Group on Civilian Biodefense, USAMRIID) recommend that asymptomatic individuals with exposure to plague aerosol or asymptomatic individuals with household, hospital, or other close contact (within about 2 m) with an individual who has pneumonic plague should receive postexposure anti-infective prophylaxis; however, any exposed individual who develops a temperature of 38.5°C or higher or new cough should promptly receive a parenteral anti-infective for treatment of the disease.7,256,258 An oral regimen of doxycycline or ciprofloxacin usually is recommended for such prophylaxis;256,258 although efficacy has not been established, co-trimoxazole has been recommended for prophylaxis in children younger than 8 years of age.7

Tularemia

Treatment

Gentamicin is used in the treatment of tularemia† caused by Francisella tularensis .6,7,51,52,76,258 Although streptomycin generally is considered the drug of choice for this infection,6,51,52,76,257,258 gentamicin is more readily available and may be used as an alternative drug of choice when streptomycin is unavailable.51,52,76,257,258 Other alternatives for the treatment of tularemia include tetracyclines (doxycycline), chloramphenicol, or ciprofloxacin.6,7,51,52,257,258

Anti-infective regimens recommended for the treatment of naturally occurring or endemic tularemia also are recommended for the treatment of tularemia that occurs following exposure to F. tularensis in the context of biologic warfare or bioterrorism.51,257 However, the fact that a fully virulent streptomycin-resistant strain of F. tularensis was developed in the past for use in biologic warfare should be considered.257 Exposures to F. tularensis in the context of biologic warfare or bioterrorism would most likely result in inhalational tularemia with pleuropneumonitis, although the organism also can infect humans through the skin, mucous membranes, and GI tract.257

Prophylaxis

Postexposure prophylaxis with anti-infectives usually is not recommended after possible exposure to natural or endemic tularemia (e.g., tick bite, rabbit or other animal exposure) and is unnecessary in close contacts of tularemia patients since human-to-human transmission of the disease is not known to occur.257,258 However, postexposure prophylaxis is recommended following a high-risk laboratory exposure to F. tularensis (e.g., spill, centrifuge accident, needlestick injury).257 In the context of biologic warfare or bioterrorism, some experts (e.g., the US Working Group on Civilian Biodefense, USAMRIID, BICHAT) recommend that asymptomatic individuals with exposure to F. tularensis receive postexposure anti-infective prophylaxis; however, any individual who develops an otherwise unexplained fever or flu-like illness within 14 days of presumed exposure should promptly receive a parenteral anti-infective for treatment of the disease.51,257,258 Oral doxycycline (or oral tetracycline) or oral ciprofloxacin usually is recommended for postexposure prophylaxis following such exposures;257,258 streptomycin or gentamicin also have been recommended for postexposure prophylaxis of tularemia†.7

Empiric Therapy in Febrile Neutropenic Patients

Gentamicin is used for empiric anti-infective therapy of presumed bacterial infections in febrile neutropenic patients†.6,44 Gentamicin is used in conjunction with an appropriate antipseudomonal cephalosporin (e.g., ceftazidime, ceftriaxone, cefepime), extended-spectrum penicillin (e.g., piperacillin and tazobactam, ticarcillin and clavulanate), or carbapenem (e.g., imipenem, meropenem).6,44 Gentamicin should not be used alone for empiric therapy in febrile neutropenic patients.44

Published protocols for the treatment of infections in febrile neutropenic patients should be consulted for specific recommendations regarding selection of the initial empiric regimen, when to change the initial regimen, possible subsequent regimens, and duration of therapy in these patients.44 Consultation with an infectious disease expert knowledgeable about infections in immunocompromised patients also is advised.44

Perioperative Prophylaxis

Gentamicin is used in conjunction with clindamycin for perioperative prophylaxis† in patients undergoing head and neck surgery (incisions through oral or pharyngeal mucosa).70,71 In addition, in patients who cannot receive β-lactams, a regimen of vancomycin with or without gentamicin has been recommended as an alternative for perioperative prophylaxis in those undergoing vascular surgery and a regimen of clindamycin or metronidazole with gentamicin has been recommended as an alternative for perioperative prophylaxis in those undergoing gynecologic and obstetric surgery.87

Gentamicin also is used as an adjunct to cefoxitin or cefotetan (no longer commercially available in the US) in patients undergoing contaminated or dirty surgery†, such as that involving a perforated abdominal viscus.70 When used in patients undergoing these procedures, anti-infective therapy often is considered treatment rather than prophylaxis and is continued postoperatively for about 5-7 days.70 There is some evidence that a shorter course of anti-infectives (12-24 hours) may be as effective as a 5-day regimen in patients with penetrating abdominal and intestinal injuries.70

If gentamicin is used perioperatively, the fact that concurrent use of aminoglycosides and general anesthetics or neuromuscular blocking agents may potentiate neuromuscular blockade and cause respiratory paralysis should be considered.1,2,3,4 5,6,7,8,10,11,12,13,15,19,20,21 (See Drug Interactions: General Anesthetics and Neuromuscular Blocking Agents in the Aminoglycosides General Statement 8:12.02.)

Administration

Gentamicin sulfate is administered by IM injection or IV infusion.1,2,3,4 IV administration may be preferred in patients with septicemia, shock, congestive heart failure, hematologic disorders, severe burns, or reduced muscle mass.1,2,3,4

Gentamicin sulfate has been administered intrathecally† or intraventricularly† as an adjunct to IM or IV administration of the drug for the treatment of meningitis and other CNS infections.5,18

Patients should be well hydrated prior to and during gentamicin therapy since dehydration increases the risk of toxicity.1,2,3,4

Renal function should be assessed prior to and monitored during gentamicin therapy.1,2,3,4 Patients should be under close clinical observation because of the risk of ototoxicity and nephrotoxicity.1,2,3,4 (See Cautions in the Aminoglycosides General Statement 8:12.02.)

Prior to administration, gentamicin solutions should be inspected visually for particulate matter or discoloration.1,2,3,4

IM Injection

For IM injection, the appropriate dose of commercially available injection containing gentamicin in a concentration of 10 or 40 mg/mL should be withdrawn from the vial and given undiluted.1,2

The commercially available gentamicin injection in 0.9% sodium chloride should not be used for IM administration of the drug.3,4

IV Infusion

IV infusions for adults are prepared from commercially available injections containing gentamicin in a concentration of 10 or 40 mg/mL by diluting the appropriate dose of gentamicin with 50-200 mL of 0.9% sodium chloride or 5% dextrose injection.1,2 For pediatric patients, the volume of infusion fluid depends on the patient's needs, but should be sufficient to allow a gentamicin infusion period of 30 minutes to 2 hours.1,2

Alternatively, the appropriate dose of premixed gentamicin solution in 0.9% sodium chloride injection can be used; however, these premixed solutions may not be appropriate for the dosage requirements of neonates, infants, or children.3,4 The commercially available premixed solutions should not be diluted or buffered prior to administration and should be given only by IV infusion.3,4 Premixed gentamicin solution in 0.9% sodium chloride injection is provided in single-dose flexible containers; additives should not be introduced into the injection container and the containers should not be used in series.3,4 However, if the dose needed is greater or less than that in the container, the manufacturer states that the appropriate amount of gentamicin sulfate solution can be introduced into or removed from the container.4 The manufacturer's instructions should be consulted for proper use of commercially available premixed gentamicin sulfate in 0.9% sodium chloride injection.3,4

Gentamicin should not be admixed with other drugs or infused simultaneously through the same tubing with other drugs.1,2,3,4 If a β-lactam anti-infective (e.g., cephalosporin, penicillin) is administered concomitantly with gentamicin, the drugs should not be admixed and should be administered separately.1,2,3,4

Rate of Administration

IV infusions of gentamicin should be given over 30 minutes to 2 hours.1,2,3,4

Intrathecal or Intraventricular Administration

If gentamicin is administered intrathecally† or intraventricularly†, a preservative-free preparation of the drug should be used.10,64

Dosage

Dosage of gentamicin sulfate is expressed in terms of gentamicin.1,2,3,4 IM and IV dosage is identical.1,2,3,4

Like other aminoglycosides, dosage of gentamicin should be individualized taking into consideration the patient's pretreatment body weight, renal status, severity of the infection, and susceptibility of the causative organism.1,2,3,4,214,215,216,217,218 The manufacturers state that dosage in obese patients should be based on the patient's estimated lean body weight.1,2,3,4 Many clinicians recommend that gentamicin dosage be determined using appropriate pharmacokinetic methods for calculating dosage requirements and patient-specific pharmacokinetic parameters (e.g., elimination rate constant, volume of distribution) derived from serum concentration-time data.21,41,42,37,61,214,215,216,217,218,242,243,244,245,246,247,248,249

Whenever possible, especially in patients with life-threatening infections, suspected toxicity or nonresponse to treatment, decreased or varying renal function, and/or when increased aminoglycoside clearance (e.g., patients with cystic fibrosis, burns) or prolonged therapy is likely, peak and trough serum concentrations of gentamicin should be determined periodically and dosage should be adjusted to maintain desired serum concentrations.1,2,3,4,5,11,235,236,237,238,239,240,241,242,250 (See Dosage and Administration: Dosage, in the Aminoglycosides General Statement 8:12.02.) A causal relationship between maintenance of certain peak or trough serum concentrations or other pharmacodynamic endpoints and clinical response or toxicity has not been established to date for gentamicin dosing regimens.219,220,232,233,234 However, for gentamicin administered in conventional dosage regimens (i.e., multiple daily doses), peak serum concentrations of 4-10 mcg/mL and trough concentrations that do not exceed 1-2 mcg/mL have been suggested.5,10,11,17,21,22,36,64,88 An increased risk of toxicity may be associated with peak serum gentamicin concentrations greater than 10-12 mcg/mL and/or trough concentrations greater than 2 mcg/mL.1,2,3,4,11 The manufacturers state that prolonged peak serum concentrations greater than 12 mcg/mL and trough concentrations greater than 2 mcg/mL should be avoided.1,2,3,4

Parenteral aminoglycosides historically have been administered in dosage regimens that include multiple daily doses,5,10,230 and current prescribing information for IM or IV gentamicin only includes dosage regimens that involve multiple daily doses (usually 3 or 4 doses daily).1,2,3,4 However, there is evidence that once-daily† (single-daily) aminoglycoside dosage regimens are at least as effective as, may provide superior pharmacokinetics, and may be less toxic than conventional dosage regimens employing multiple daily doses of the drugs.5,10,27,58,62,65,98,109,218,219,220,221,222,223,224,225,226,227,228,229,230,231,251,252,253,254 Although once-daily gentamicin regimens are recommended for some indications,5,10,62,256,257,258 once-daily gentamicin regimens should not be used in all patients5,103 and should not be used for the treatment of enterococcal or staphylococcal endocarditis†.19 Additional controlled studies in children, patients with renal dysfunction, and other appropriate patient groups are needed to fully define the optimal use of once-daily aminoglycoside dosing regimens.98,218,219,221,222,223,224,230,243,246,249,253,254 In addition, the most appropriate methods for optimizing dosage selection for once-daily regimens and monitoring serum aminoglycoside concentrations in patients receiving such regimens have not been clearly established.23,24,25,27,29,32,38,58,59,60,100,102,103,104,105,106,107,108,251,253 (See Dosage and Administration: Dosage, in the Aminoglycosides General Statement 8:12.02.)

The usual duration of gentamicin treatment is 7-10 days.1,2,3,4 In difficult and complicated infections, a longer course of treatment may be necessary.1,2,3,4 However, toxicity is more likely to occur if treatment is continued for longer than 10 days and renal, auditory, and vestibular functions should be monitored closely.1,2,3,4

Adult Dosage

General Adult Dosage

If IM or IV gentamicin is used for the treatment of serious infections caused by susceptible bacteria in adults with normal renal function, the usual adult dosage recommended by the manufacturers is 3 mg/kg daily given in 3 equally divided doses every 8 hours.1,3,4 For life-threatening infections in adults with normal renal function, the manufacturers state that an IM or IV gentamicin dosage up to 5 mg/kg daily given in 3 or 4 equally divided doses may be used, but dosage should be reduced to 3 mg/kg daily as soon as clinically indicated.1,3,4

If a once-daily† gentamicin regimen is used in adults with normal renal function, some clinicians recommend a dosage of 4-5 mg/kg once daily.5,62 A once-daily regimen of 5-7 mg/kg once daily also has been recommended.10 It has been suggested that, if gentamicin is used alone for the treatment of serious infections (e.g., without concomitant use of a β-lactam), a dosage of 7 mg/kg once daily usually is required.5

Endocarditis Treatment

For the treatment of native or prosthetic valve enterococcal endocarditis†, the American Heart Association (AHA) and Infectious Diseases Society of America (IDSA) recommend that adults receive IM or IV gentamicin in a dosage of 3 mg/kg daily given in 3 equally divided doses in conjunction with IV ampicillin sodium (12 g daily in 6 equally divided doses) or IV penicillin G sodium (18-30 million units daily).19 In patients with native valve enterococcal endocarditis caused by strains susceptible to penicillin and gentamicin, treatment should be continued for 4-6 weeks; although a 4-week regimen may be used in those who have had symptoms of infection for 3 months or less prior to initiation of treatment, a 6-week regimen is recommended for those who have had symptoms for longer than 3 months.19 In patients with prosthetic valve or other prosthetic cardiac material, treatment should be continued for a minimum of 6 weeks.19 In those with enterococci susceptible to penicillins, gentamicin, and vancomycin who are unable to tolerate penicillins, a 6-week regimen of IM or IV gentamicin (3 mg/kg daily given in 3 equally divided doses) should be used in conjunction with a 6-week regimen of IV vancomycin (30 mg/kg daily given in 2 equally divided doses).19 If penicillin-resistant enterococci are involved, the AHA and IDSA recommend that adults receive a 6-week regimen of IM or IV gentamicin (3 mg/kg daily given in 3 equally divided doses) in conjunction with a 6-week regimen of IV ampicillin sodium and sulbactam sodium (12 g of ampicillin daily given in 4 equally divided doses) or IV vancomycin (30 mg/kg daily given in 2 equally divided doses).19 Pending further accumulation of data, the AHA and IDSA state that once-daily gentamicin regimens should not be used for the treatment of enterococcal endocarditis.19

If a 2-week regimen is appropriate for the treatment of native valve endocarditis caused by viridans streptococci or S. bovis † highly susceptible to penicillin (i.e., penicillin MIC of 0.12 mcg/mL or less) (see Endocarditis Caused by Viridans Streptococci or S. bovis in Uses: Endocarditis), the AHA and IDSA recommend that adults receive IM or IV gentamicin in a dosage of 3 mg/kg given once daily or in 3 equally divided doses for 2 weeks in conjunction with a 2-week regimen of IV penicillin G sodium (12-18 million units daily) or IV or IM ceftriaxone (2 g once daily).19 For the treatment of native valve endocarditis caused by viridans streptococci or S. bovis relatively resistant to penicillins (i.e., penicillin MIC greater than 0.12 mcg/mL and less than or equal to 0.5 mcg/mL), AHA and IDSA recommend that adults receive a 2-week regimen of IM or IV gentamicin in a dosage of 3 mg/kg given once daily or in 3 equally divided doses in conjunction with a 4-week regimen of IV penicillin G sodium (24 million units daily) or IV or IM ceftriaxone (2 g once daily).19 If prosthetic valves or other prosthetic materials are involved and viridans streptococci or S. bovis is penicillin susceptible (i.e., penicillin MIC of 0.12 mcg/mL or less), the AHA and IDSA recommend a 2-week regimen of IM or IV gentamicin in a dosage of 3 mg/kg once daily or in 3 equally divided doses in conjunction with a 6-week regimen of IV penicillin G sodium (24 million units daily) or IV or IgivenM ceftriaxone (2 g once daily).19 However, if the organisms are relatively or fully resistant to penicillins (i.e., penicillin MIC greater than 0.12 mcg/mL), then IM or IV gentamicin in a dosage of 3 mg/kg given once daily or in 3 equally divided doses should be continued for 6 weeks in conjunction with a 6-week regimen of IV penicillin G sodium (24 million units daily) or IV or IM ceftriaxone (2 g once daily).19

If gentamicin is used as an adjunct to a β-lactam for the treatment of native valve staphylococcal endocarditis†, the AHA and IDSA recommend an IM or IV gentamicin dosage of 3 mg/kg daily given in 2 or 3 equally divided doses during the first 3-5 days of a 6-week regimen of IV nafcillin or oxacillin (12 g daily given in 4-6 equally divided doses) or IV cefazolin (6 g daily given in 3 equally divided doses).19 For the treatment of prosthetic valve staphylococcal endocarditis, the AHA and IDSA recommend that adults receive a 2-week regimen of IM or IV gentamicin in a dosage of 3 mg/kg daily given in 2 or 3 equally divided doses in conjunction with at least 6 weeks of IV nafcillin or oxacillin (12 g daily given in 6 equally divided doses) or, for oxacillin-resistant (methicillin-resistant) strains, IV vancomycin (30 mg/kg daily given in 3 equally divided doses); either regimen should also include IV or oral rifampin (900 mg daily given in 3 equally divided doses for at least 6 weeks).19 Pending further accumulation of data, the AHA and IDSA state that once-daily gentamicin regimens should not be used for the treatment of staphylococcal endocarditis.19

Endocarditis Prevention

For prevention of endocarditis† in patients at high risk undergoing certain genitourinary tract and nonesophageal GI procedures (see Prophylaxis of Bacterial Endocarditis under Uses: Prophylaxis in the Aminopenicillins General Statement 8:12.16.08), the AHA and others recommend that adults receive an IM or IV dose of gentamicin (1.5 mg/kg up to 120 mg) and a dose of ampicillin (2 g IM or IV) administered at separate sites within 30 minutes of starting the procedure; 6 hours later, adults should receive a dose of ampicillin (1 g IM or IV) or amoxicillin (1 g orally) given without gentamicin.202

For prevention of endocarditis† in penicillin-allergic patients at high risk undergoing certain genitourinary tract or nonesophageal GI procedures, the AHA and others recommend that adults receive an IM or IV dose of gentamicin (1.5 mg/kg up to 120 mg) and a dose of vancomycin (1 g IV) administered at separate sites within 30 minutes of starting the procedure; follow-up doses are not necessary in these patients.202

Meningitis

If gentamicin is used for the treatment of meningitis, some clinicians recommend that adults receive 5 mg/kg daily given in 3 divided doses.67

An intrathecal† or intraventricular† gentamicin dosage of 4-8 mg once daily has been recommended for the treatment of meningitis in adults.10,64,67

Urinary Tract Infections

If gentamicin is used for the treatment of uncomplicated urinary tract infections caused by susceptible bacteria when other less toxic anti-infectives cannot be used, a dosage of 160 mg of gentamicin IM once daily has been recommended.5 A single 5-mg/kg IM dose of gentamicin has been used for the treatment of uncomplicated urinary tract infections.10

Pelvic Inflammatory Disease

For the treatment of acute pelvic inflammatory disease† (PID) when a parenteral regimen is indicated, adolescents and adults with normal renal function may receive an initial IM or IV gentamicin dose of 2 mg/kg followed by 1.5 mg/kg every 8 hours given in conjunction with clindamycin (900 mg IV every 8 hours).201,212 Although once-daily gentamicin regimens (e.g., 3 mg/kg once daily) have not been evaluated in the treatment of PID, such regimens have been efficacious in analogous situations.201,212 The parenteral gentamicin and clindamycin regimen can be discontinued 24 hours after clinical improvement occurs and treatment switched to an oral regimen (i.e., oral doxycycline or oral clindamycin) to complete a total of 14 days of therapy.201,212

Bartonella Infections

For the treatment of serious Bartonella infections† (e.g., endocarditis known or suspected of being caused by B. henselae , bacteremia or pericardial infusion caused by B. quintana ), IV gentamicin has been given in a dosage of 3 mg/kg daily in conjunction with other anti-infectives (e.g., doxycycline, ceftriaxone, amoxicillin, penicillin G benzathine, oxacillin, vancomycin).78,79,80,81 Gentamicin has been given for at least the first 14 days and the other anti-infectives continued for up to about 6 weeks.78,81

Granuloma Inguinale (Donovanosis)

When gentamicin is used as an adjunct to a recommended oral anti-infective (doxycycline, azithromycin, ciprofloxacin, erythromycin, co-trimoxazole) for the treatment of granuloma inguinale (donovanosis)† caused by Klebsiella granulomatis (formerly Calymmatobacterium granulomatis ), the CDC recommends that gentamicin be given in a dosage of 1 mg/kg IV every 8 hours.201

Donovanosis usually is treated with an oral anti-infective regimen given for at least 3 weeks and until all lesions have healed.201 If improvement is not evident within the first few days of the oral regimen, IV gentamicin should be added.201 Adjunctive use of IV gentamicin also should be considered for the treatment of Donovanosis in pregnant or lactating women and HIV-infected individuals.201 Relapse can occur 6-18 months after apparently effective therapy.201

Plague

For the treatment of plague†, including pneumonic plague that occurs as the result of exposure to Yersinia pestis in the context of biologic warfare or bioterrorism, the recommended dosage of gentamicin in adults with normal renal function is 5 mg/kg IM or IV once daily or, alternatively, adults may receive a 2-mg/kg loading dose following by 1.75 mg/kg IM or IV every 8 hours.256,258 A dosage of 2.5 mg/kg IM twice daily has been effective in some patients.90

The usual duration of therapy for the treatment of plague is 10 days;256 some experts recommend a duration of at least 10-14 days.258

Tularemia

For the treatment of tularemia† that occurs as the result of exposure to Francisella tularensis in the context of biologic warfare or bioterrorism, the US Working Group on Civilian Biodefense recommends that adults with normal renal function receive a gentamicin dosage of 5 mg/kg IM or IV once daily for 10 days.257 The US Army Medical Research Institute of Infectious Diseases (USAMRIID) recommends that adults receive 5 mg/kg IM or IV once daily or, alternatively, a 2-mg/kg loading dose following by 1.7 mg/kg IM or IV every 8 hours for at least 10-14 days.258

Perioperative Prophylaxis

For perioperative prophylaxis in patients undergoing head and neck surgery†, some clinicians recommend that a gentamicin dose of 1.5 mg/kg be given IV in conjunction with IV clindamycin (600-900 mg) immediately prior to surgery; this may be repeated if surgery is prolonged or major blood loss occurs.70 Postoperative doses of prophylactic drugs generally are unnecessary.70 Other clinicians recommend a gentamicin dose of 1.7 mg/kg given IV and a dose of clindamycin (600 mg IV) given at the time of induction of anesthesia and repeated twice at 8-hour intervals for a total of 3 doses.71

For prophylaxis following contaminated or dirty surgery, such as surgery involving a perforated abdominal viscus†, gentamicin is given IV in a dosage of 1.5 mg/kg every 8 hours in conjunction with cefoxitin (1-2 g IV every 6 hours).70 When used in this situation, the regimen may be continued postoperatively for about 5 days and is considered treatment rather than prophylaxis.70

Pediatric Dosage

General Dosage for Neonates

When IM or IV gentamicin is used in premature or full-term neonates 1 week of age or younger, the manufacturers recommend 2.5 mg/kg every 12 hours.1,2 For neonates older than 1 week of age, the manufacturers recommend a dosage of 2.5 mg/kg every 8 hours.1,2

The American Academy of Pediatrics (AAP) recommends that neonates younger than 1 week of age receive IM or IV gentamicin in a dosage of 2.5 mg/kg every 18-24 hours if they weigh less than 1.2 kg or 2.5 mg/kg every 12 hours if they weigh 1.2 kg or more.7 For neonates 1-4 weeks of age, the AAP recommends a dosage of 2.5 mg/kg every 18-24 hours for those weighing less than 1.2 kg, 2.5 mg/kg every 8 or 12 hours for those weighing 1.2-2 kg, and 2.5 mg/kg every 8 hours for those weighing more than 2 kg.7 The AAP states that the drug is inappropriate for the treatment of mild to moderate infections.7

Once-daily† gentamicin regimens have been used in neonates.22,26,39,56,57,65,72,109 Neonates have received 4-5 mg/kg of gentamicin once daily by IV infusion over 30-60 minutes.26,39,56,57,65,72,109

General Dosage for Infants and Children

The usual dosage of IM or IV gentamicin recommended by the manufacturers for older infants with normal renal function is 2.5 mg/kg every 8 hours.1,2 The manufacturers recommend that children receive gentamicin in a dosage of 2-2.5 mg/kg every 8 hours.1,2

The AAP recommends that pediatric patients beyond the neonatal period receive gentamicin in a dosage of 3-7.5 mg/kg daily given in 3 equally divided doses for the treatment of severe infections.7 The AAP states that the drug is inappropriate for the treatment of mild to moderate infections.7

Once-daily† gentamicin regimens have been used in infants and children.98,109 The AAP states that a gentamicin regimen of 5-6 mg/kg once every 24 hours is investigational in children.7 In clinical studies, children have received gentamicin in a dosage of 4.5-7.5 mg/kg once daily.98,109

Endocarditis Treatment

For the treatment of native or prosthetic valve enterococcal endocarditis†, the AHA and IDSA recommend that children receive IM or IV gentamicin in a dosage of 3 mg/kg daily given in 3 equally divided doses in conjunction with IV ampicillin sodium (300 mg/kg daily given in 4-6 equally divided doses) or IV penicillin G sodium (300,000 units/kg daily given in 4-6 equally divided doses).19 In patients with native valve enterococcal endocarditis caused by strains susceptible to penicillin, gentamicin, and vancomycin, treatment should be continued for 4-6 weeks; although a 4-week regimen may be used in those who have had symptoms of infection for 3 months or less prior to initiation of treatment, a 6-week regimen is recommended for those who have had symptoms for longer than 3 months.19 In patients with prosthetic valve or other prosthetic cardiac material, treatment should be continued for a minimum of 6 weeks.19 In children with enterococci susceptible to penicillin, gentamicin, and vancomycin who are unable to tolerate penicillins, a 6-week regimen of IM or IV gentamicin (3 mg/kg daily given in 3 equally divided doses) should be used in conjunction with a 6-week regimen of IV vancomycin (40 mg/kg daily given in 2 or 3 equally divided doses).19 If penicillin-resistant enterococci are involved, the AHA and IDSA recommend that children receive a 6-week regimen of IM or IV gentamicin (3 mg/kg daily given in 3 equally divided doses) in conjunction with a 6-week regimen of IV ampicillin sodium and sulbactam sodium (300 mg/kg daily of ampicillin given in 4 equally divided doses) or IV vancomycin (40 mg/kg daily given in 2 or 3 equally divided doses).19 Pending further accumulation of data, the AHA and IDSA state that once-daily gentamicin regimens should not be used for the treatment of enterococcal endocarditis.19

If a 2-week regimen is appropriate for the treatment of native valve endocarditis caused by viridans streptococci or S. bovis † highly susceptible to penicillin (i.e., penicillin MIC of 0.12 mcg/mL or less) (see Endocarditis Caused by Viridans Streptococci or S. bovis in Uses: Endocarditis), the AHA and IDSA recommend that children receive IM or IV gentamicin in a dosage of 3 mg/kg daily in 1 or 3 equally divided doses for 2 weeks in conjunction with a 2-week regimen of IV penicillin G sodium (200,000 units/kg daily in 4-6 equally divided doses) or IV or IM ceftriaxone (100 mg/kg once daily).19 For the treatment of native valve endocarditis caused by viridans streptococci or S. bovis relatively resistant to penicillins (i.e., penicillin MIC greater than 0.12 mcg/mL and less than or equal to 0.5 mcg/mL), AHA and IDSA recommend that children receive IM or IV gentamicin in a dosage of 3 mg/kg daily in 1 or 3 equally divided doses for 2 weeks in conjunction with a 4-week regimen of IV penicillin G sodium (200,000 units/kg daily in 4-6 equally divided doses) or IV or IM ceftriaxone (100 mg/kg once daily).19 If prosthetic valves or other prosthetic materials are involved and viridans streptococci or S. bovis is penicillin susceptible, the AHA and IDSA recommend that children receive a 2-week regimen of IM or IV gentamicin in a dosage of 3 mg/kg daily in 1 or 3 equally divided doses in conjunction with a 6-week regimen of IV penicillin G sodium (300,000 units/kg daily given in 4-6 equally divided doses) or IM or IV ceftriaxone (100 mg/kg once daily).19 However, if the organisms are relatively or fully resistant to penicillins, then gentamicin (3 mg/kg daily in 1 or 3 equally divided doses) should be continued for 6 weeks in conjunction with the 6-week regimen of IV penicillin G sodium (200,000 units/kg daily in 4-6 equally divided doses) or IV or IM ceftriaxone (100 mg/kg once daily).19

If gentamicin is used as an adjunct to a β-lactam for the treatment of native valve staphylococcal endocarditis†, the AHA and IDSA recommend that children receive IM or IV gentamicin in a dosage of 3 mg/kg daily given in 3 equally divided doses for the first 3-5 days of a 6-week regimen of IV nafcillin or oxacillin (200 mg/kg daily given in 4-6 equally divided doses) or IV cefazolin (100 mg/kg daily given in 3 equally divided doses).19 For the treatment of prosthetic valve staphylococcal endocarditis, the AHA and IDSA recommend that children receive a 2-week regimen of IM or IV gentamicin in a dosage of 3 mg/kg daily given in 3 equally divided doses in conjunction with at least 6 weeks of IV nafcillin or oxacillin (200 mg/kg daily given in 4-6 equally divided doses) or, for oxacillin-resistant strains, IV vancomycin 40 mg/kg daily given in 2 or 3 equally divided doses); either regimen should also include IV or oral rifampin (20 mg/kg daily given in 3 equally divided doses for at least 6 weeks).19 Pending further accumulation of data, the AHA and IDSA state that once-daily gentamicin regimens should not be used for the treatment of staphylococcal endocarditis.19

Endocarditis Prevention

For prevention of endocarditis† in patients at high risk undergoing certain genitourinary or nonesophageal GI tract procedures (see Prophylaxis of Bacterial Endocarditis under Uses: Prophylaxis in the Aminopenicillins General Statement 8:12.16.08), the AHA, AAP, and others recommend that children receive an IM or IV dose of gentamicin (1.5 mg/kg up to 120 mg) and an IM or IV dose of ampicillin (50 mg/kg up to 2 g) administered at separate sites within 30 minutes of starting the procedure; 6 hours later, a dose of ampicillin (25 mg/kg IM or IV) or amoxicillin (25 mg/kg orally) should be given without gentamicin.7,202

For prevention of endocarditis† in penicillin-allergic patients at high risk undergoing certain genitourinary or nonesophageal GI tract procedures, the AHA, AAP, and others recommend that children receive a dose of IM or IV gentamicin (1.5 mg/kg up to 120 mg) and a dose of vancomycin (20 mg/kg given IV over 1-2 hours) at separate sites and completed within 30 minutes of starting the procedure; follow-up doses are not necessary in these patients.7,202

Meningitis

For the treatment of meningitis, some clinicians recommend that neonates 7 days of age or younger receive a parenteral gentamicin dosage of 5 mg/kg daily given in 2 divided doses and that older neonates and children receive a parenteral dosage of 7.5 mg/kg daily given in 3 divided doses.67,74 Smaller doses and longer intervals between doses may be indicated in neonates weighing less than 2 kg.67,74

An intrathecal† or intraventricular† gentamicin dosage of 1-2 mg once daily has been recommended for children older than 3 months of age.64,67

Plague

For the treatment of plague†, including pneumonic plague that occurs as the result of exposure to Yersinia pestis in the context of biologic warfare or bioterrorism, the US Working Group on Civilian Biodefense and USAMRIID recommend that children with normal renal function receive gentamicin in a dosage of 2.5 mg/kg IM or IV 3 times daily;256,258 neonates up to 1 week of age and premature neonates should receive a dosage of 2.5 mg/kg IV twice daily.256 A dosage of 2.5 mg/kg IM twice daily has been effective in some patients.90

The usual duration of therapy for the treatment of plague is 10 days;256 some experts recommend a duration of at least 10-14 days.258

Tularemia

For the treatment of tularemia† that occurs as the result of exposure to Francisella tularensis in the context of biologic warfare or bioterrorism, the US Working Group on Civilian Biodefense and USAMRIID recommend that children with normal renal function receive gentamicin in a dosage of 2.5 mg/kg IM or IV every 8 hours.257,258

For the treatment of naturally occurring or endemic tularemia†, children have received gentamicin in a dosage of 5-7.5 mg/kg daily given in 3 divided doses.76

The usual duration of therapy for the treatment of tularemia is 10 days;257,258 some experts recommend a duration of at least 10-14 days.258

Urinary Tract Infections

For the treatment of uncomplicated urinary tract infections in children, a single 5-mg/kg IM dose† of gentamicin (up to 300 mg) has been used.68 The drug should not be used for uncomplicated infections unless other less toxic anti-infectives cannot be used.1,2,3,4

Dosage in Renal Impairment

In patients with impaired renal function, doses and/or frequency of administration must be modified in response to serum concentrations of the drug and the degree of renal impairment.1,2,3,4,5,11,14,20,33 There are various methods to determine dosage and a wide variation in dosage recommendations for these patients.1,2,3,4,5,11,14,33 However, even when one of these methods is used, peak and trough serum concentrations of the drug should be monitored, especially in patients with changing renal function.1,2,3,4,11

The manufacturers recommend that adults with renal impairment receive an initial dose of 1-1.7 mg/kg.1,3,4 For subsequent therapy, the manufacturers state that 1 mg/kg doses can be given at intervals (in hours) calculated by multiplying the patient's steady-state serum creatinine (in mg/dL) by 8.1,3,4 Alternatively, many clinicians recommend the dosing method of Sarubbi and Hull, which is based on corrected creatinine clearance. (See Dosage and Administration: Dosage in Renal Impairment, in the Aminoglycosides General Statement 8:12.02.) These dosage calculation methods should not be used in patients undergoing hemodialysis or peritoneal dialysis.

In adults with renal failure undergoing hemodialysis, the manufacturers recommend supplemental doses of 1-1.7 mg/kg at the end of each dialysis period in adults1,2,3,4 and supplemental doses of 2-2.5 mg/kg at the end of each dialysis period in children.1,2 Some clinicians suggest supplemental doses of 50-75% of the initial loading dose at the end of each dialysis period.11 Serum gentamicin concentrations should be monitored in dialysis patients and dosage adjusted as needed to maintain desired serum concentrations.1,2,3,4,11

Pharmacokinetics

The pharmacokinetics of gentamicin are similar to those of the other aminoglycosides.5,10,11,88 In all studies described in the Pharmacokinetics section, gentamicin was administered as the sulfate salt; dosages and concentrations of the drug are expressed in terms of gentamicin.

Absorption

Gentamicin is poorly absorbed from the GI tract and must be administered parenterally.10

Gentamicin is rapidly absorbed following IM administration.10 Following IM administration of a single 1-mg/kg dose of gentamicin in adults with normal renal function, peak serum gentamicin concentrations of 4-7.6 mcg/mL are attained within 30-90 minutes.1,2,3,4,10,12,17

Serum concentrations attained following IV infusion over 20 minutes to 2 hours usually are similar to those attained when the same dose is given by IM injection.1,2,3,4,5,15 When gentamicin is administered by IV infusion over 2 hours, peak serum concentrations usually occur at 30-60 minutes and are measurable for 6-8 hours.4

In neutropenic adults who received gentamicin in a once-daily regimen of 4.5 mg/kg once every 24 hours by IV infusion over 30 minutes, peak serum gentamicin concentrations averaged 10.9, 7.1, 4.2, 1.8, and 0.16 mcg/mL at 1, 2, 4, 8, and 24 hours after the infusion.40

In infants, peak serum gentamicin concentrations of 3-5 mcg/mL are attained 30-60 minutes following a single 2.5-mg/kg IM dose.2 A single 1-mg/kg IV dose in children 6 months to 5 years of age, 5-10 years of age, or older than 10 years of age resulted in mean peak serum concentrations of 1.58, 2.03, and 2.81 mcg/mL, respectively.2,17

Serum concentrations may be lower in febrile patients and in seriously ill patients, including those with anemia, severe burns, or malignancy.1,2,3,4

Accumulation of gentamicin does not appear to occur in patients with normal renal function receiving 1-mg/kg doses every 8 hours for 7-10 days.1,3,4 However, accumulation may occur with higher doses and/or when the drug is given for prolonged periods, especially in patients with renal impairment.1,2,3,4

Distribution

Following parenteral administration of usual dosages of gentamicin, the drug can be detected in lymph,1,2,3,4 subcutaneous tissue,1,2,3,4,30 lung,55 sputum,1,2,3,4 and bronchial,5 pleural,1,2,3,4,5 pericardial,5 synovial,1,2,3,4,5 ascitic,5 and peritoneal fluids.1,2,3,4 Concentrations in bile may be low, suggesting minimal biliary excretion.1,2,3,4 In patients with ventilator-associated pneumonia receiving IV gentamicin (240 mg once daily), drug concentrations in alveolar lining fluid were 32% of serum concentrations and averaged 4.24 mcg/mL 2 hours after a dose.55

Only minimal concentrations of gentamicin are attained in ocular tissue following IM or IV administration.1,2,3,4

Gentamicin is distributed into CSF in low concentrations following IM or IV administration.1,2,3,4,5 CSF concentrations of gentamicin following intrathecal administration depend on the dose administered, the site of injection, the volume in which the dose is diluted, and the presence or absence of obstruction to CSF flow.18 There may be considerable interpatient variation in concentrations achieved.18 In one study, intrathecal administration of 4 mg of gentamicin resulted in CSF concentrations of the drug of 19-46 mcg/mL for 8 hours and less than 3 mcg/mL at 20 hours.18

Gentamicin crosses the placenta.1,2,3,4,5,54

Gentamicin is distributed into milk following IM administration.53,54

Elimination

The plasma elimination half-life of gentamicin is usually 2-4 hours in adults with normal renal function5,11,13,14,15,88 and is reported to range from 24-60 hours in adults with severe renal impairment.5,11,14

The serum half-life of gentamicin averages 3-3.5 hours in infants 1 week to 6 months of age and 5.5 hours in full-term infants and large premature infants less than 1 week of age.2 In small premature infants, the plasma half-life is approximately 5 hours in those weighing over 2 kg, 8 hours in those weighing 1.5-2 kg, and 11.5 hours in those weighing less than 1.5 kg.2

Gentamicin clearance may be decreased in geriatric patients compared with other adults.5

In adults with normal renal function, 50-93% of a single IM dose of gentamicin is excreted unchanged by glomerular filtration within 24 hours.1,3,4,5,10,12,15 Peak urine concentrations of gentamicin may range from 113-423 mcg/mL 1 hour after a single IM dose of 1 mg/kg in adults with normal renal function.12 Complete recovery of the dose in urine requires approximately 10-20 days in patients with normal renal function, and terminal elimination half-lives of greater than 100 hours have been reported in adults with normal renal function following repeated IM or IV administration of the drug.

Gentamicin is removed by hemodialysis and peritoneal dialysis.5,14

Chemistry and Stability

Chemistry

Gentamicin is an aminoglycoside antibiotic obtained from cultures of Micromonospora purpurea .1,2,3,4,9,97 The commercially available drug is a mixture of the sulfate salts of gentamicin C₁, C₂, and C_1A.1,2,3,4,97 Gentamicin sulfate occurs as a white to buff powder and is freely soluble in water and insoluble in alcohol.9

Commercially available gentamicin sulfate injection for IM or IV administration is a clear, colorless to slightly yellow solution;8,9 sodium hydroxide and/or sulfuric acid may be added during manufacture1,2 to adjust the pH to 3-5.5.2,9 Each mL of injection containing 40 mg of gentamicin per mL also contains 1.8 mg of methylparaben and 0.2 mg of propylparaben as preservatives, 3.2 mg of sodium metabisulfite, and 0.1 mg of edetate disodium.1 Each mL of injection containing 10 mg of gentamicin per mL in multiple-dose vials contains 1.3 mg of methylparaben, 0.2 mg of propylparaben, 3.2 mg of sodium metabisulfite, and 0.1 mg of edetate disodium.2 Injections containing 10 mg of gentamicin per mL in single-dose vials do not contain preservatives.2

Commercially available premixed gentamicin sulfate in 0.9% sodium chloride injection for IV use is an isotonic solution with a pH of approximately 4 (3-5.5); sodium hydroxide and/or sulfuric acid may be added during manufacture to adjust the pH.3,4 These injections are isotonic3,4 with a calculated osmolarity of 290 mOsm/L.4

Stability

Commercially available gentamicin sulfate injections for IM or IV administration containing 40 mg of gentamicin per mL should be stored at 15-30°C and those containing 10 mg/mL should be stored at 20-25°C.1,2 Commercially available premixed gentamicin sulfate in 0.9% sodium chloride injection for IV use in Viaflex^® Plus or PAB^® plastic containers should be stored at controlled room temperature of 25°C, but may be exposed briefly to temperatures up to 40°C.3,4 These injections should not be frozen.4

Gentamicin sulfate is stable for 24 hours at room temperature in most IV infusion fluids including 0.9% sodium chloride or 5% dextrose injection.8 Gentamicin sulfate injections should not be mixed with other drugs.1,2,3,4,8

The commercially available premixed gentamicin sulfate in 0.9% sodium chloride injection for IV use is provided in plastic containers fabricated from specially formulated polyvinyl chloride (Viaflex^® Plus)3 or from a rubberized copolymer of ethylene and propylene (PAB^®).4 Safety of these plastics has been confirmed in tests in animals according to USP biological tests for plastic containers as well as by tissue culture toxicity studies.3,4

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.For further information on chemistry and stability, mechanism of action, spectrum, resistance, pharmacokinetics, uses, cautions, drug interactions, and dosage and administration of gentamicin, see the Aminoglycosides General Statement 8:12.02. For topical uses of gentamicin, see 52:04.04 and 84:04.04.

Only references cited for selected revisions after 1984 are available electronically.

1. American Pharmaceutical Partners. Gentamicin injection, USP (40 mg/mL) prescribing information. Schaumburg, IL; 2004 Jan.

2. American Pharmaceutical Partners. Gentamicin injection (pediatric), USP (10 mg/mL) prescribing information. Schaumburg, IL; 2004 Jul.

3. Baxter Healthcare Corp. Isotonic gentamicin sulfate injection in Viaflex plus plastic container (40, 60, 80, 100,120 mg gentamicin in 50 mL or 100 mL) prescribing information. Deerfield, IL; 2003 Oct.

4. B Braun Medical Inc. Gentamicin sulfate in 0.9% sodium chloride injection (60, 80, 100 mg gentamicin in 50 mL or 100 mL) prescribing information. Irvine, CA; 2004 Oct.

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