VA Class:AM119
Meropenem is a synthetic carbapenem β-lactam antibiotic1, 2, 3 that is structurally and pharmacologically related to imipenem, but does not require concomitant administration with a dehydropeptidase 1 (DHP 1) inhibitor such as cilastatin.2, 3, 11, 12
Meropenem is used for the treatment of intra-abdominal infections, meningitis, and skin and skin structure infections caused by susceptible bacteria.1 The drug also is used for the treatment of respiratory tract infections†, 19, 20, 21, 22, 23, 24, 26, 27 septicemia†, 24 and urinary tract infections†24, 38 caused by susceptible bacteria19 and for empiric anti-infective therapy in febrile neutropenic patients†.14
Prior to initiation of meropenem therapy, appropriate specimens should be obtained for identification of the causative organism and in vitro susceptibility tests.1 Meropenem can be initiated empirically pending completion of susceptibility testing, with continuance or alteration (e.g., substitution of an appropriate alternative anti-infective) determined by the results of culture and susceptibility tests.1
Meropenem is used for the treatment of intra-abdominal infections, including complicated appendicitis and peritonitis, caused by susceptible bacteria.1, 2, 3, 4, 6, 7, 9, 10, 12, 24, 28, 43 The drug may be used as monotherapy for the treatment of intra-abdominal infections caused by susceptible viridans streptococci, Escherichia coli , Klebsiella pneumonia , Pseudomonas aeruginosa , Bacteroides fragilis , B. thetaiotaomicron , or Peptostreptococcus .1, 2, 3, 4, 6, 43 Because meropenem has a broad spectrum of antibacterial activity, the drug may be used empirically to treat intra-abdominal infections before identification of the causative organism.1, 2, 6, 7, 10
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 that has a narrower spectrum of activity since unnecessary use of broad spectrum agents in such infections may contribute to emergence of resistance.28 Therefore, IDSA recommends use 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, gatifloxacin) in conjunction with metronidazole for treatment of mild to moderate community-acquired intra-abdominal infections.28 Patients who are immunosuppressed or have more severe community-acquired intra-abdominal infections, however, should receive a regimen that has a broader spectrum of activity.28 Regimens recommended by IDSA for such individuals include meropenem monotherapy; imipenem and cilastatin monotherapy; a third or fourth generation cephalosporin (cefotaxime, ceftriaxone, ceftizoxime, ceftazidime, cefepime) in conjunction with metronidazole; ciprofloxacin in conjunction with metronidazole; the fixed combination of piperacillin and tazobactam; or aztreonam in conjunction with metronidazole.28 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.24 These clinicians state that an aminoglycoside also could be included in the empiric regimen;24 however, IDSA states that aminoglycosides should not be used routinely in patients with community-acquired intra-abdominal infections but may be included in empiric regimens for treatment of nosocomial intra-abdominal infections, depending on local patterns of in vitro susceptibility of nosocomial isolates.28 Postoperative (nosocomial) intra-abdominal infections usually require treatment with multiple-drug regimens and, since these infections often involve resistant organisms, IDSA recommends that empiric regimens be selected based on local nosocomial susceptibility patterns.28
In clinical studies in patients with intra-abdominal infections, meropenem monotherapy was similar in efficacy to a 2-drug regimen of tobramycin and clindamycin or monotherapy with imipenem and cilastatin sodium.1, 2, 3, 4, 5, 6, 9, 12, 43 At follow-up 7 or more days after empiric anti-infective therapy was completed, clinical cure was achieved in 69, 76, or 65% of evaluable patients treated with meropenem, tobramycin combined with clindamycin, or imipenem and cilastatin, respectively, and the respective rate of microbiologic eradication was 67, 76, or 62%.1 In one study, meropenem monotherapy was less effective than a 2-drug regimen of cefotaxime and metronidazole for empiric treatment of complicated intra-abdominal infections; however, the difference in efficacy may have resulted from uneven assignment of patients with more severe infection to the group that received meropenem.1
Meropenem is used for the treatment of bacterial meningitis caused by susceptible Streptococcus pneumoniae , Haemophilus influenzae (including β-lactamase-producing strains), or Neisseria meningitidis in children 3 months of age and older.1, 2, 8, 10, 25, 29, 30, 44 The drug also is used in the treatment of meningitis in adults†.29, 46 Efficacy of meropenem for the treatment of meningitis caused by highly penicillin- or cephalosporin-resistant S. pneumoniae has not been established.1, 29, 44, 45
Meropenem can be used as monotherapy for the treatment of meningitis caused by susceptible bacteria.1 Although meropenem usually is not considered an initial drug of choice, it is recommended as an alternative agent in children and adults for the treatment of meningitis caused by S. pneumoniae , H. influenzae , and various other bacteria24, 25, 29, 30 and may be useful for meningitis caused by susceptible gram-negative bacteria (e.g., Enterobacter †, Citrobacter †, Serratia marcescens †) that are resistant to usually recommended regimens.29
IDSA states that meropenem monotherapy is one of several alternatives that can be used for empiric treatment of meningitis in adults† when the causative organism has been presumptively identified by CSF gram stain as S. pneumoniae , H. influenzae , Listeria monocytogenes †, or E. coli †, and the regimens of choice cannot be used.29 In addition, if in vitro susceptibility tests indicate that the causative organism is susceptible to meropenem, IDSA states that the drug can be used as an alternative to penicillin G, ampicillin, or third generation cephalosporins (ceftriaxone or cefotaxime) for the treatment of meningitis caused by S. pneumoniae or N. meningitidis (only if the strains have penicillin MICs of 1 mcg/mL or less), as an alternative to penicillin G or ampicillin for meningitis caused by L. monocytogenes †, as an alternative to third generation cephalosporins (ceftriaxone or cefotaxime) for meningitis caused by E. coli † or other Enterobacteriaceae†, as an alternative to cefepime or ceftazidime for meningitis caused by Ps. aeruginosa †, or as an alternative to nafcillin or oxacillin for meningitis caused by oxacillin-susceptible (methicillin-susceptible) S. aureus .29 IDSA also recommends meropenem used in conjunction with vancomycin as one of several regimens of choice for empiric therapy in patients with purulent meningitis associated with penetrating head trauma, recent neurosurgery, or a CSF shunt.29
In clinical studies that included children who were at least 3 months of age but younger than 17 years of age, clinical cure of bacterial meningitis was achieved in 78% of those receiving meropenem monotherapy (40 mg/kg IV every 8 hours) or 77% of those receiving monotherapy with usual dosages of cefotaxime or ceftriaxone.1 When results were stratified according to the most frequent causative organisms, the clinical cure rate in those receiving meropenem or a comparator drug was 71 or 63%, respectively, if meningitis was caused by S. pneumoniae ; 80 or 100%, respectively, if caused by β-lactamase-producing H. influenzae ; 75 or 73%, respectively, if caused by H. influenzae that either did not produce β-lactamase or was not tested for such; and 86 or 90%, respectively, if caused by N. meningitidis .1 Sequelae was the most common reason patients were assessed as clinically not cured;1 a few patients receiving meropenem were considered not cured because of relapse or continued growth of Ps. aeruginosa .1
Meropenem is used in the treatment of respiratory tract infections†, including community-acquired pneumonia (CAP) and nosocomial pneumonia, caused by susceptible bacteria.19, 20, 21, 22, 23, 24, 26, 27
Although meropenem generally is active against S. pneumoniae (including drug-resistant S. pneumoniae ), the American Thoracic Society (ATS), IDSA, and other clinicians state that the drug usually is considered an alternative, not a drug of first choice, for empiric treatment of CAP† caused by S. pneumoniae .19, 20, 23, 26 ATS and IDSA suggest that use of meropenem in the treatment of CAP be reserved for when the infection may be caused by Ps. aeruginosa ,20, 23 Klebsiella ,23 or other gram-negative bacteria.23 Factors that increase the risk of Ps. aeruginosa infection in CAP patients include severe CAP requiring treatment in an intensive care unit (ICU), structural lung disease (bronchiectasis, cystic fibrosis), corticosteroid therapy (prednisone dosage exceeding 10 mg daily), broad-spectrum anti-infective therapy given for longer than 7 days within the past month, and malnutrition.20 In CAP patients with risk factors for Ps. aeruginosa , the empiric regimen should include 2 antipseudomonal agents and also provide coverage for drug-resistant S. pneumoniae and Legionella .20, 23 The ATS and IDSA suggest that this can be accomplished with a regimen that includes an IV antipseudomonal β-lactam anti-infective (e.g., cefepime, piperacillin and tazobactam, imipenem, meropenem) in conjunction with an IV antipseudomonal fluoroquinolone (e.g., ciprofloxacin) or a regimen that includes one of these IV antipseudomonal β-lactam anti-infectives, an IV aminoglycoside, and either an IV macrolide (e.g., azithromycin) or an IV nonpseudomonal quinolone.19, 23
If anaerobic bacteria have been identified or are suspected in patients with pulmonary infections, IDSA recommends use of clindamycin, a β-lactam/β-lactamase inhibitor combination, imipenem, or meropenem.19
Meropenem is considered a drug of choice for empiric treatment of nosocomial pneumonia†.24, 26 ATS, IDSA, and other clinicians recommend use of an antipseudomonal cephalosporin (cefepime, ceftazidime), antipseudomonal penicillin (piperacillin and tazobactam, ticarcillin and clavulanate), or an antipseudomonal carbapenem (imipenem or meropenem) for initial therapy of hospital-acquired pneumonia, ventilator-associated pneumonia, or health-care associated pneumonia because these drugs have a broad spectrum of activity against gram-positive, gram-negative, and anaerobic bacteria.24, 26, 27 In severely ill patients or in those with late-onset disease or risk factors for multidrug-resistant bacteria, the initial regimen should also include an aminoglycoside (amikacin, gentamicin, tobramycin) or antipseudomonal fluoroquinolone (ciprofloxacin or levofloxacin) to improve coverage against Pseudomonas .24, 26 In hospitals where oxacillin-resistant (methicillin-resistant) Staphylococcus are common or if there are risk factors for these strains, the initial regimen also should include vancomycin or linezolid.24, 26, 27 In hospitals where multidrug-resistant Ps. aeruginosa are frequent causes of nosocomial pneumonia, some clinicians suggest that the initial regimen of choice is cefepime or a carbapenem (imipenem or meropenem) in conjunction with an aminoglycoside.26, 54
Meropenem has been used for the treatment of septicemia† caused by susceptible bacteria.24 There is evidence that concurrent bacteremia associated with bacterial meningitis has been eliminated during meropenem meningitis treatment.1, 8
The choice of anti-infective agent for the treatment of sepsis syndrome should be based on the probable source of infection, gram-stained smears of appropriate clinical specimens, the immune status of the patient, and current patterns of bacterial resistance within the hospital and local community.24 For the treatment of gram-negative sepsis, a parenteral third or fourth generation cephalosporin (cefepime, cefotaxime, ceftizoxime, ceftriaxone, ceftazidime), an antipseudomonal penicillin (piperacillin and tazobactam or ticarcillin and clavulanate), a carbapenem (imipenem or meropenem), or aztreonam can be used.24 The antipseudomonal penicillins or carbapenems offer the advantages of activity against most strains of Ps. aeruginosa and activity against anaerobes.24 For initial treatment of life-threatening sepsis in adults, some clinicians recommend a regimen that includes either a parenteral third or fourth generation cephalosporin (cefepime, cefotaxime, ceftriaxone, ceftazidime), the fixed combination of piperacillin and tazobactam, or a carbapenem (imipenem or meropenem) in conjunction with an aminoglycoside (amikacin, gentamicin, tobramycin).24 Vancomycin (alone or in conjunction with gentamicin and/or rifampin) may be included in the initial regimen if oxacillin-resistant (methicillin-resistant) S. epidermidis is suspected.24
Skin and Skin Structure Infections
Meropenem is used for the treatment of complicated skin and skin structure infections caused by susceptible Staphylococcus aureus (including β-lactamase-producing strains, but not oxacillin-resistant [methicillin-resistant] strains), S. pyogenes (group A β-hemolytic streptococci), S. agalactiae (group B streptococci), viridans streptococci, Enterococcus faecalis (except vancomycin-resistant strains), Ps. aeruginosa , E. coli , Proteus mirabilis , B. fragilis , or Peptostreptococcus .1
Some clinicians state that reasonable choices for empiric treatment of complicated skin and skin structure infections are imipenem, meropenem, the fixed combination of piperacillin and tazobactam, or the fixed combination of ticarcillin and clavulanate; however, vancomycin or linezolid should be included in the empiric regimen whenever oxacillin-resistant (methicillin-resistant) S. aureus may be involved.24, 54
Safety and efficacy of meropenem for the treatment of complicated skin and skin structure infections were evaluated in a randomized, double-blind trial in adults with complicated cellulitis, complex abscesses, perirectal abscesses, or infections requiring IV anti-infectives, hospitalization, and surgical intervention (37% had diabetes, 12% had peripheral vascular disease, 67% required surgical intervention).1 Patients were randomized to receive meropenem (500 mg IV every 8 hours) or imipenem and cilastatin (500 mg of imipenem IV every 8 hours).1 In clinically evaluable patients, the success rate at follow-up was 86% in those who received meropenem and 83% in those who received imipenem.1 In the group that received meropenem, the clinical cure rate was 90-93% for infections caused by S. aureus (oxacillin-susceptible strains), S. pyogenes , or viridans streptococci; 71 or 75% for those caused by S. agalactiae or E. faecalis , respectively; 80 or 85% for those caused by E. coli or P. mirabilis , respectively; 73% for those caused by Ps. aeruginosa ; and 91 or 77% for those caused by B. fragilis or Peptostreptococcus , respectively.1
Although safety and efficacy have not been established, meropenem has been used for the treatment of complicated urinary tract infections† caused by susceptible bacteria.38 Some clinicians suggest that urinary tract infections in hospitalized patients should be treated with a third generation cephalosporin, a fluoroquinolone, fixed combination of ticarcillin and clavulanate, fixed combination of piperacillin and tazobactam, imipenem, or meropenem; an aminoglycoside should be used concomitantly, especially in patients with sepsis.24 (See Uses: Septicemia.)
Meropenem used alone or in conjunction with an aminoglycoside (amikacin, gentamicin, tobramycin) is a drug of choice for the treatment of infections caused by Acinetobacter †.24
Although data are not available regarding in vivo activity of meropenem against Bacillus anthracis , the drug has in vitro activity against the organism,40 and it has been suggested that meropenem is one of several anti-infectives that can be included in multiple-drug regimens used for the treatment of anthrax†, including inhalational anthrax and anthrax meningitis.31, 39
Based on clinical experience from the bioterrorism-related anthrax exposures of 2001 and the possibility that a B. anthracis strain resistant to one or more anti-infectives might be used in a future bioterrorism event, CDC and other experts (e.g., US Working Group on Civilian Biodefense) recommend that treatment of clinically apparent inhalational anthrax in adults, adolescents, or children that occurs as the result of exposure to anthrax spores in the context of biologic warfare or bioterrorism be initiated with a multiple-drug parenteral regimen that includes ciprofloxacin or doxycycline and 1 or 2 additional anti-infectives predicted to be effective.31, 41, 42 Other drugs to be included in the initial treatment regimen with ciprofloxacin or doxycycline should be selected based on in vitro susceptibility, possibility of efficacy, adverse effects, and cost.31, 41 Based on in vitro data, other drugs that have been suggested as possibilities to augment ciprofloxacin or doxycycline in such multiple-drug regimens include chloramphenicol, clindamycin, rifampin, vancomycin, clarithromycin, imipenem, meropenem, penicillin, or ampicillin.31, 41, 42 Optimum regimens for treatment of anthrax meningitis are unknown.39 However, if meningitis is established or suspected, early and aggressive anti-infective treatment is critical.39 Some clinicians suggest a multiple-drug regimen that includes a fluoroquinolone (e.g., ciprofloxacin) and 2 additional agents with good CSF penetration (e.g., ampicillin or penicillin,39, 41 meropenem,39 rifampin,39, 41 vancomycin39 ).
For information on treatment of anthrax and recommendations for prophylaxis following exposure to anthrax spores, see Uses: Anthrax, in Ciprofloxacin 8:12.18.
Meropenem is used for the treatment of infections caused by Bacillus cereus †.24 Although vancomycin is considered the drug of choice, carbapenems (imipenem or meropenem) or clindamycin are alternatives.24
Meropenem is used as an alternative to imipenem or ceftazidime for the treatment of melioidosis† caused by Burkholderia pseudomallei .24, 31, 32, 33, 34
B. pseudomallei may cause subclinical illness and localized infections or fulminant septicemia; disseminated infections may include hepatic and splenic abscesses.25, 31 The incubation period usually is 1-21 days; however, in some asymptomatic individuals, the disease has remained dormant for prolonged periods and active melioidosis was not evident for up to 29 years later, usually at a time when the patient was immunosuppressed.31 If left untreated, severe septicemic infections can be fatal within 24-48 hours after onset.31 B. pseudomallei is widely distributed in water and soil in many tropical and subtropical countries and melioidosis is endemic in Southeast Asia and northern Australia.31 Person-to-person spread occurs only rarely.31, 34 B. pseudomallei usually is transmitted to humans from contaminated materials (e.g., soil) via contact with nasal, oral, or conjunctival mucous membranes, contact with abraded or lacerated skin, or, rarely, by inhalation.31 Laboratory workers have become infected via aerosols from B. pseudomallei cultures.31
Patients with localized or mild disease may be effectively treated with a prolonged regimen of oral anti-infectives (e.g., oral doxycycline in conjunction with oral co-trimoxazole).31 However, patients with severe illness should receive an initial parenteral regimen of ceftazidime, imipenem, or meropenem (some clinicians recommend that co-trimoxazole also be included, especially if the patient is septicemic) followed by a prolonged maintenance regimen of oral anti-infectives (e.g., co-trimoxazole with or without doxycycline).31, 32, 33, 34 (See Burkholderia Infections under Dosage and Administration: Adult Dosage.) In patients with melioidosis septic shock, adjunctive use of filgrastim (granulocyte colony-stimulating factor; G-CSF) during initial treatment has been suggested.31, 33 After the maintenance regimen is completed, life-long follow-up is recommended since relapse of melioidosis can occur despite effective anti-infective therapy.31
B. pseudomallei has been studied for and is considered a potential pathogen for aerosol distribution in the context of biologic warfare or bioterrorism.31, 34 Acute respiratory or systemic infection probably would occur following high-dose aerosol exposure to B. pseudomallei .31 Some experts (e.g., US Army Medical Research Institute of Infectious Diseases [USAMRIID], European Commission's Task Force on Biological and Chemical Agent Threats [BICHAT]) state that the same treatment regimens recommended for naturally occurring melioidosis should be used if the disease occurs in the context of biologic warfare or bioterrorism.31, 34
Meropenem has been recommended for the treatment of glanders† caused by B. mallei .31, 34
Human infection with B. mallei is rare and has occurred principally in veterinarians, horse and donkey caretakers, and abattoir workers exposed to infected animals (usually horses, mules, or donkeys).31, 34 There have been no naturally acquired cases of human glanders reported in the US for more than 50 years, and the disease currently is reported only sporadically in Asia, Africa, the Middle East, and South America.31 B. mallei occurs only in infected, susceptible hosts, and the transmission rate from infected animals to humans appears to be low.31 Person-to-person spread occurs only rarely.34
Because experience is limited regarding the treatment of human cases of glanders, optimum regimens have not been identified.31 Some clinicians suggest that streptomycin in conjunction with a tetracycline is the regimen of choice and alternatives are streptomycin in conjunction with chloramphenicol or imipenem monotherapy.24 Other clinicians suggest that, pending results of in vitro susceptibility tests, regimens recommended for treatment of melioidosis can be used for initial empiric treatment of glanders since these Burkholderia species are similar and efficacy data are available regarding use of these regimens in patients with melioidosis.31
B. mallei has been studied for and is considered a possible pathogen for aerosol distribution in the context of biologic warfare or bioterrorism.31, 34 Some experts (e.g., USAMRIID, BICHAT) state that the same treatment regimens recommended for naturally occurring glanders should be used if the disease occurs in the context of biologic warfare or bioterrorism.31, 34
Meropenem is used for the treatment of systemic infections caused by Campylobacter fetus †.24 Some clinicians suggest that the drug of choice for these infections is a third generation cephalosporin or gentamicin, and alternatives are ampicillin, imipenem, or meropenem.24
Meropenem has been recommended for the treatment of infections caused by Capnocytophaga canimorsus †.24
Optimum regimens for the treatment of infections caused by Capnocytophaga have not been identified.24 Some clinicians recommend use of penicillin G or, alternatively, a third generation cephalosporin (cefotaxime, ceftizoxime, ceftriaxone), a carbapenem (imipenem or meropenem), vancomycin, a fluoroquinolone, or clindamycin.24
Meropenem is recommended by some clinicians as an alternative to penicillin G for the treatment of infections caused by Clostridum perfringens † in individuals with penicillin hypersensitivity or for polymicrobial infections.24, 25
Meropenem is used for the treatment of infections caused by Nocardia †.24, 25 Co-trimoxazole usually is considered the drug of first choice for Nocardia infections;24, 25 alternatives include sulfisoxazole, a tetracycline (e.g., doxycycline, minocycline), a carbapenem (imipenem or meropenem), amikacin, ceftriaxone, fixed combination of amoxicillin and clavulanate, cycloserine, or linezolid.24, 25 In vitro susceptibility testing, if available, is recommend for isolates from patients with invasive disease and those unable to tolerate a sulfonamide.25
Meropenem in conjunction with vancomycin is recommended for the treatment of infections caused by Rhodococcus equi †.24 Optimum regimens for these infections have not been identified.24 Some clinicians suggest that the regimen of choice is vancomycin with or without a fluoroquinolone, rifampin, a carbapenem (imipenem or meropenem), or amikacin.24
Empiric Therapy in Febrile Neutropenic Patients
Meropenem is used alone or in conjunction with other anti-infectives for empiric anti-infective therapy of presumed bacterial infections in febrile neutropenic patients†.14, 24
Successful treatment of infections in granulocytopenic patients requires prompt initiation of empiric anti-infective therapy (even when fever is the only sign or symptom of infection) and appropriate modification of the initial regimen if the duration of fever and neutropenia is protracted, if a specific site of infection is identified, or if organisms resistant to the initial regimen are present.14, 15, 16, 17 The initial empiric regimen should be chosen based on the underlying disease and other host factors that may affect the degree of risk and on local epidemiologic data regarding usual pathogens in these patients and data regarding their in vitro susceptibility to available anti-infective agents.14, 15, 17, 18 The fact that gram-positive bacteria have become a predominant pathogen in febrile neutropenic patients should be considered when selecting an empiric anti-infective regimen.14, 15, 17
No empiric regimen has been identified that would be appropriate for all patients.14, 15, 17 Regimens that have been recommended for empiric therapy in febrile neutropenic patients with presumed bacterial infections include monotherapy with a third or fourth generation cephalosporin (i.e., ceftazidime, cefepime) or a carbapenem (e.g., imipenem and cilastatin sodium, meropenem) or combination therapy consisting of a β-lactam antibiotic (e.g., ceftazidime, ceftriaxone), a carbapenem (e.g., imipenem, meropenem), an extended-spectrum penicillin (e.g., ticarcillin), or a fixed combination of an extended-spectrum penicillin and a β-lactamase inhibitor (e.g., piperacillin and tazobactam, ticarcillin and clavulanate) given in conjunction with an aminoglycoside (e.g., amikacin, gentamicin, tobramycin).14, 15, 16, 17, 18
IDSA recommends use of a parenteral empiric regimen in most febrile neutropenic patients; use of an oral regimen (e.g., oral ciprofloxacin and oral amoxicillin and clavulanate) should be considered only in selected adults at low risk for complications who have no focus of bacterial infection and no signs or symptoms of systemic infection other than fever.14 At health-care facilities where gram-positive bacteria are common causes of serious infection and use of vancomycin in the initial empiric regimen is considered necessary, IDSA recommends 2- or 3-drug combination therapy that includes vancomycin and either cefepime, ceftazidime, imipenem, or meropenem given with or without an aminoglycoside; vancomycin should be discontinued 24-48 hours later if a susceptible gram-positive bacterial infection is not identified.14 At health-care facilities where vancomycin is not indicated in the initial empiric regimen, IDSA recommends monotherapy with a third or fourth generation cephalosporin (ceftazidime, cefepime) or a carbapenem (imipenem, meropenem) for uncomplicated cases; however, for complicated cases or if anti-infective resistance is a problem, combination therapy consisting of an aminoglycoside (amikacin, gentamicin, tobramycin) given in conjunction with an antipseudomonal penicillin (ticarcillin and clavulanate, piperacillin and tazobactam), an antipseudomonal cephalosporin (cefepime, ceftazidime), or a carbapenem (imipenem, meropenem) is recommended.14 Regardless of the initial regimen selected, patients should be reassessed after 3-5 days of treatment and the anti-infective regimen altered (if indicated) based on the presence or absence of fever, identification of the causative organism, and the clinical condition of the patient.14
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.14
Meropenem is administered by IV injection or IV infusion.1
For direct intermittent IV injection, 10 or 20 mL of sterile water for injection should be added to a vial labeled as containing 500 mg or 1 g, respectively, of meropenem to provide a solution containing approximately 50 mg/mL.1 The vial should be shaken until dissolution occurs and then allowed to stand until the solution is clear.1 Reconstituted solutions should be used promptly, but may be stored for up to 2 hours at 15-25°C or up to 12 hours at 4°C.1
For IV infusion, vials labeled as containing 500 mg or 1 g of meropenem should be diluted in a compatible IV solution.1 Alternatively, vials labeled as containing 500 mg or 1 g may be reconstituted as directed for direct intermittent IV injection and the resulting solution added to an IV container and further diluted with a compatible IV solution.1
IV injections of meropenem should be given over a 3- to 5-minute period.1
IV infusions of meropenem should be given over approximately 15-30 minutes.1
Meropenem is commercially available as the trihydrate; potency and dosage of the drug are expressed on the anhydrous basis.13
To minimize the risk of seizures, recommended meropenem dosage should not be exceeded, especially in patients with factors known to predispose to seizure activity.1 (See CNS Effects under Warning/Precautions: Warnings, in Cautions.)
The usual adult dosage of meropenem for the treatment of intra-abdominal infections is 1 g every 8 hours.1
For the treatment of bacterial meningitis in adults†, some clinicians recommend a dosage of 6 g daily.29 A dosage of 40 mg/kg every 8 hours daily (up to 6 g daily) has been used in conjunction with ceftriaxone or cefotaxime in adults with meningitis.46
If meropenem is used for the treatment of nosocomial pneumonia† (including hospital-acquired, ventilator-associated, or health-care-associated infections), some clinicians recommend that adults receive a dosage of 1 g every 8 hours.27
Skin and Skin Structure Infections
The usual adult dosage of meropenem for the treatment of complicated skin and skin structure infections is 500 mg every 8 hours.1
For the treatment of severe melioidosis† caused by Burkholderia pseudomallei , the US Army Medical Research Institute of Infectious Diseases (USAMRIID) and other clinicians recommend a meropenem dosage of 25 mg/kg IV every 8 hours (up to 6 g daily); concomitant co-trimoxazole (8 mg/kg of trimethoprim daily given in 4 divided doses) may be indicated in septicemic individuals.31, 32, 33 Other clinicians recommend a meropenem dosage of 0.5-1 g every 8 hours with or without co-trimoxazole.34 The initial parenteral regimen should be continued for at least 14 days and until there is clinical improvement.31, 32, 33 Although the median time to fever resolution is 9 days, some patients may remain febrile for prolonged periods despite appropriate antimicrobial therapy.31 When appropriate, treatment may be changed to an oral maintenance regimen (e.g., oral co-trimoxazole with or without oral doxycycline) and continued for at least 3-6 months to prevent recrudence or relapse.31, 33 More prolonged oral maintenance therapy (up to 12 months) may be necessary, depending on the response to therapy and severity of initial illness.31
Although only limited experience is available regarding the treatment of human cases of glanders†, some clinicians suggest that the meropenem regimens recommended for the treatment of severe melioidosis also can be used for the treatment of glanders.31
Children weighing more than 50 kg should receive the usually recommended adult dosage of meropenem.1
For the treatment of intra-abdominal infections, children 3 months of age and older weighing 50 kg or less should receive 20 mg/kg (up to 1 g) every 8 hours.1
For the treatment of meningitis, children 3 months of age and older weighing 50 kg or less should receive 40 mg/kg (up to 2 g) every 8 hours.1
Skin and Skin Structure Infections
For the treatment of complicated skin and skin structure infections, children 3 months of age and older weighing 50 kg or less should receive 10 mg/kg (up to 500 mg) every 8 hours.1
Some clinicians suggest that children older than 3 months of age can receive meropenem in a dosage of 10-20 mg/kg every 8 hours for the initial treatment of melioidosis† caused by B. pseudomallei or glanders† caused by B. mallei .34 Concomitant therapy with co-trimoxazole may be indicated in those with severe illness.34 These clinicians state that children weighing more than 40 kg may receive the meropenem dosage recommended for adults with these infections.34 (See Burkholderia Infections under Dosage and Administration: Adult Dosage.)
The manufacturer states that dosage adjustment is not necessary for geriatric patients with creatinine clearances exceeding 50 mL/minute.1 For geriatric patients with reduced renal function, dosage should be adjusted according to the guidelines for other adults with renal impairment.1 (See Dosage in Renal and Hepatic Impairment under Dosage and Administration: Dosage.)
Dosage in Renal and Hepatic Impairment
Dosage of meropenem should be modified according to the degree of renal impairment in adults with creatinine clearances of 50 mL/minute or less.1, 47, 48, 50 The manufacturer and some clinicians recommend that adults with creatinine clearances of 26-50 mL/minute can receive the usual dose every 12 hours, those with creatinine clearances of 10-25 mL/minute can receive half the usual dose every 12 hours, and those with creatinine clearances less than 10 mL/minute can receive half the usual dose every 24 hours.1, 48 If a measured creatinine clearance is unavailable, the patient's creatinine clearance (Ccr) can be estimated using the following formulas:
Ccr male = [(140 - age) × weight (in kg)] / [72 × serum creatinine (in mg/dL)]
Ccr female = 0.85 × Ccr male
Because meropenem is removed by hemodialysis,47, 48, 50, 60 supplemental doses should be given after each hemodialysis session.47, 48 Meropenem also is removed by various forms of continuous renal replacement therapy, including continuous venovenous hemodiafiltration (CVVHDF), continuous venovenous hemofiltration (CVVHF), and continuous ambulatory peritoneal dialysis (CAPD).49, 50, 51, 52, 53 Therefore, to avoid inadequate meropenem concentrations in anuric patients undergoing these procedures, dosage adjustments are necessary and should be based on characteristics of the specific procedure (e.g., filter or membrane type, amount of filtrate produced, dialysate flow rate).49, 50, 51, 52, 53
The manufacturer states that there is a lack of experience with use of meropenem in pediatric patients with renal impairment.1 Some clinicians suggest that pediatric patients undergoing hemodialysis receive meropenem doses after hemodialysis.60
Dosage adjustment is not necessary in patients with hepatic impairment.1
Known hypersensitivity to meropenem, other carbapenems, or any ingredient in the formulation.1
History of anaphylactic reaction to β-lactams.1
Superinfection/Clostridium difficile-associated Colitis
Possible emergence and overgrowth of nonsusceptible organism.1 Careful observation of the patient is essential.1 Institute appropriate therapy if superinfection occurs.1
Treatment with anti-infectives may permit overgrowth of clostridia.1 Consider Clostridium difficile -associated diarrhea and colitis (antibiotic-associated pseudomembranous colitis) if diarrhea develops and manage accordingly.1
Some mild cases of C. difficile -associated diarrhea and colitis may respond to discontinuance alone.1, 56, 57, 58, 59 Manage moderate to severe cases with fluid, electrolyte, and protein supplementation; appropriate anti-infective therapy (e.g., oral metronidazole or vancomycin) recommended if colitis is severe.1, 56, 57, 58, 59
Seizures and other adverse CNS effects reported during meropenem therapy, especially in those with underlying CNS disorders (e.g., brain lesions, history of seizures), bacterial meningitis, or compromised renal function.1
Do not exceed recommended dosage, especially in those with known factors that predispose to seizures.1 Anticonvulsant therapy should be continued in those with known seizure disorders.1
If focal tremors, myoclonus, or seizures occur, evaluate the patient neurologically, initiate anticonvulsant therapy if necessary, and determine whether meropenem dosage should be decreased or the drug discontinued.1
Serious and occasionally fatal hypersensitivity reactions (e.g., anaphylaxis) reported with β-lactams.1
If hypersensitivity occurs, discontinue meropenem and institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, and maintenance of an adequate airway and oxygen).1
Partial cross-allergenicity among β-lactam antibiotics, including penicillins, cephalosporins, and other β-lactams.1
Prior to initiation of meropenem therapy, make careful inquiry concerning previous hypersensitivity reactions to meropenem, cephalosporins, penicillins, or other drugs.1
Selection and Use of Anti-infectives
To reduce development of drug-resistant bacteria and maintain effectiveness of meropenem and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.1
When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.1 In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.1
Periodically assess organ system functions, including renal, hepatic, and hematopoietic, during prolonged therapy.1
Each g of meropenem contains 3.92 mEq (90.2 mg) of sodium as sodium carbonate.1
Category B.1 (See Users Guide)
Not known whether meropenem is distributed into milk.1 Use with caution.1
Safety and efficacy not established in children younger than 3 months of age.1
No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.1
Substantially eliminated by kidneys; risk of toxicity may be greater in patients with impaired renal function.1 Select dosage with caution and assess renal function periodically since geriatric patients are more likely to have renal impairment.1
No dosage adjustments except those related to renal function.1 (See Dosage in Renal and Hepatic Impairment under Dosage and Administration: Dosage.)
Pharmacokinetics not affected by hepatic impairment; dosage adjustments not required.1
Decreased clearance.1 Dosage adjustments recommended in patients with creatinine clearance less than 50 mL/minute.1 (See Dosage in Renal and Hepatic Impairment under Dosage and Administration: Dosage.)
Adverse effects reported in 1% or more of patients receiving meropenem including GI effects (diarrhea, nausea, vomiting, constipation), local reactions (pain and inflammation at injection site, phlebitis/thrombophlebitis), headache, anemia, rash, pruritus, sepsis, apnea, shock, glossitis, and oral candidiasis.1
Potential pharmacologic interaction (synergistic antibacterial effects against Pseudomonas aeruginosa ).1
Pharmacokinetic interaction (decreased renal tubular secretion of meropenem; increased systemic exposure and prolonged meropenem half-life).1 Concomitant use not recommended.1
Pharmacokinetic interaction (valproic acid serum concentrations may be decreased to subtherapeutic concentrations; possible increased risk of seizures).1, 35, 36, 37 Use concomitantly with caution.36, 55
Meropenem is a synthetic carbapenem antibiotic structurally and pharmacologically related to other carbapenems (e.g., imipenem, ertapenem).1, 2, 3 Unlike imipenem, meropenem has a methyl group at position 1 of the 5-membered ring, which confers stability against hydrolysis by dehydropeptidase 1 (DHP 1) present on the brush border of proximal renal tubular cells and therefore does not require concomitant administration with a DHP-1 inhibitor such as cilastatin.2, 3, 11, 12
Meropenem usually is bactericidal in action.1 Like other β-lactam antibiotics, the antibacterial activity of meropenem results from inhibition of bacterial cell wall synthesis.1 Meropenem has a broad spectrum of antibacterial activity and is active against many gram-positive and -negative bacteria and some anaerobic bacteria.1 The spectrum of activity of meropenem resembles that of imipenem; however, meropenem generally is more active in vitro against Enterobacteriaceae and less active against gram-positive bacteria.2, 3 Like imipenem, meropenem is highly resistant to hydrolysis by a variety of β-lactamases (including penicillinases, cephalosporinases, and extended-spectrum β-lactamases)1, 2, 3 but appears to be more susceptible to hydrolysis by metallo-β-lactamases.2, 3
Meropenem is active in vitro and in clinical infections against many gram-positive aerobic and facultatively aerobic bacteria, including Streptococcus pneumoniae (penicillin-susceptible strains only), S. pyogenes (group A β-hemolytic streptococci), S. agalactiae (group B streptococci), Staphylococcus aureus (including β-lactamase-producing strains, but not oxacillin-resistant [methicillin-resistant] strains), Enterococcus faecalis (not vancomycin-resistant strains), and viridans streptococci.1, 2, 3 The drug also is active in vitro against S. epidermidis (including β-lactamase-producing strains, but not oxacillin-resistant strains).1
Meropenem is active in vitro and in clinical infections against many gram-negative aerobic and facultatively aerobic bacteria, including Escherichia coli , Haemophilus influenzae (including β-lactamase-producing strains), Klebsiella pneumoniae , Neisseria meningitidis , Proteus mirabilis , and Pseudomonas aeruginosa .1 The drug also is active in vitro against Acinetobacter , Aeromonas hydrophila , Campylobacter jejuni , Citrobacter diversus , C. freundii , Enterobacter cloacae , H. influenzae (ampicillin-resistant, non-β-lactamase-producing strains; BLNAR), Havnia alvei , K. oxytoca , Moraxella catarrhalis (including β-lactamase-producing strains), Morganella morganii , Pasteurella multocida , P. vulgaris , Salmonella , Shigella , Serratia marcescens , and Yersinia enterocolitica .1
Meropenem is active in vitro and in clinical infections against some anaerobic bacteria, including Bacteroides fragilis , B. thetaiotaomicron , and Peptostreptococcus .1 The drug also is active in vitro against B. distasonis , B. ovatus , B. uniformis , B. ureolyticus , B. vulgatus , Clostridium difficile , C. perfringens , Eubacterium lentum , Fusobacterium , Prevotella bivia , P. intermedia , P. melaninogenica , Porphyromonas asaccharolytica , and Propionibacterium acnes .1
Cross resistance may occur between meropenem and other carbapenems (e.g., imipenem).1
Meropenem is distributed into most body tissues and fluids, including bronchial mucosa, lung, bile, gynecologic tissue (endometrium, myometrium, ovary, cervix, fallopian tube), muscle, heart valves, skin, interstitial and peritoneal fluid, and CSF.1 Plasma protein binding is approximately 2%.1 The drug is partially metabolized to at least one microbiologically inactive metabolite.1 About 70% of an IV dose is eliminated in urine as unchanged drug1 by tubular secretion and glomerular filtration.47, 48 The plasma half-life of meropenem is approximately 1 hour in adults with normal renal function and 1.5 hours in children 3 months to 2 years of age.1 Plasma half-life is increased and clearance of the drug is decreased in patients with renal impairment.1, 47, 48, 51
Advise patients that antibacterials (including meropenem) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).1
Importance of completing full course of therapy, even if feeling better after a few days.1
Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with meropenem or other antibacterials in the future.1
Importance of informing clinicians of other medical conditions, including history of seizures.1
Importance of discontinuing therapy and informing clinician if an allergic or hypersensitivity reaction occurs.1
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and any concomitant illnesses.1
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1
Importance of informing patients of other important precautionary information.1 (See Cautions.)
Additional Information
Overview® (see Users Guide). For additional information on this drug until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | For injection, for IV use only | 500 mg (of anhydrous meropenem) | Merrem® I.V. | |
1 g (of anhydrous meropenem) | Merrem® I.V. | AstraZeneca |
1. AstraZeneca Pharmaceuticals. Merrem® IV (meropenem) for injection for intravenous use only prescribing information. Wilmington, DE; 2005 May.
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