Pediatric Patients 3 Months of Age and Older
For pediatric patients 3 months of age and older, the Meropenem for Injection dose is 10 mg/kg, 20 mg/kg or 40 mg/kg every 8 hours (maximum dose is 2 grams every 8 hours), depending on the type of infection (complicated skin and skin structure, intra-abdominal or meningitis). (See below.) Pediatric patients weighing over 50 kg should be administered Meropenem for Injection at a dose of 500 mg every 8 hours for complicated skin and skin structure infections, 1 gram every 8 hours for intra-abdominal infections and 2 grams every 8 hours for meningitis. Meropenem for Injection should be given as intravenous infusion over approximately 15 minutes to 30 minutes or as an intravenous bolus injection (5 mL to 20 mL) over approximately 3 minutes-5 minutes. For pediatric patients 3 months of age and older, the Meropenem for Injection dose is 10 mg/kg, 20 mg/kg or 40 mg/kg every 8 hours (maximum dose is 2 grams every 8 hours), depending on the type of infection (complicated skin and skin structure, intra-abdominal or meningitis). (See dosing table below.) Pediatric patients weighing over 50 kg should be administered Meropenem for Injection at a dose of 500 mg every 8 hours for complicated skin and skin structure infections, 1 gram every 8 hours for intra-abdominal infections and 2 grams every 8 hours for meningitis. Meropenem for Injection should be given as intravenous infusion over approximately 15 minutes to 30 minutes or as an intravenous bolus injection (5 mL to 20 mL) over approximately 3 minutes-5 minutes.
There is limited safety data available to support the administration of a 40 mg/kg (up to a maximum of 2 grams) bolus dose.There is limited safety data available to support the administration of a 40 mg/kg (up to a maximum of 2 grams) bolus dose.
Recommended Meropenem for Injection Dosage Schedule for Pediatric Patients 3 Months of Age and Older with Normal Renal Function| Type of Infection | Dose (mg/kg) | Up to a Maximum Dose | Dosing Interval |
|---|
| There is no experience in pediatric patients with renal impairment. |
| When treating complicated skin and skin structure infections caused by P. aeruginosa, a dose of 20 mg/kg (or 1 gram for pediatric patients weighing over 50 kg) every 8 hours is recommended. |
| Complicated skin and skin structure | 10 | 500 mg | Every 8 hours |
| Intra-abdominal | 20 | 1 gram | Every 8 hours |
| Meningitis | 40 | 2 grams | Every 8 hours |
Pediatric Patients Less Than 3 Months of Age
For pediatric patients (with normal renal function) less than 3 months of age, with intra-abdominal infections, the Meropenem for Injection dose is based on gestational age (GA) and postnatal age (PNA). (See dosing table below). Meropenem for Injection should be given as intravenous infusion over 30 minutes.
Recommended Meropenem for Injection Dosage Schedule for Pediatric Patients Less than 3 Months of Age with Complicated Intra-Abdominal Infections and Normal Renal Function| Age Group | Dose (mg/kg) | Dose Interval |
|---|
| There is no experience in pediatric patients with renal impairment. |
| Infants less than 32 weeks GA and PNA less than 2 weeks | 20 | Every 12 hours |
| Infants less than 32 weeks GA and PNA 2 weeks and older | 20 | Every 8 hours |
| Infants 32 weeks and older GA and PNA less than 2 weeks | 20 | Every 8 hours |
| Infants 32 weeks and older GA and PNA 2 weeks and older | 30 | Every 8 hours |
For Intravenous Bolus Administration
Constitute injection vials (500 mg and 1 gram) with sterile Water for Injection (see table below). Shake to dissolve and let stand until clear.
| Vial Size | Amount of
Diluent Added
(mL) | Approximate
Withdrawable Volume (mL) | Approximate
Average Concentration (mg/mL) |
|---|
| 500 mg | 10 | 10 | 50 |
| 1 gram | 20 | 20 | 50 |
For Infusion
Infusion vials (500 mg and 1 gram) may be directly constituted with a compatible infusion fluid. Alternatively, an injection vial may be constituted, then the resulting solution added to an intravenous container and further diluted with an appropriate infusion fluid [see Dosage and Administration (2.5) and (2.6)].
WARNING: Do not use flexible container in series connections.
Intravenous Bolus Administration
Meropenem for Injection vials constituted with sterile Water for Injection for bolus administration (up to 50 mg/mL of Meropenem for Injection) may be stored for up to 3 hours at up to 25°C (77°F) or for 13 hours at up to 5°C (41°F).
Intravenous Infusion Administration
Solutions prepared for infusion (Meropenem for Injection concentrations ranging from 1 mg/mL to 20 mg/mL) constituted with Sodium Chloride Injection 0.9% may be stored for 1 hour at up to 25°C (77°F) or 15 hours at up to 5°C (41°F).
Solutions prepared for infusion (Meropenem for Injection concentrations ranging from 1 mg/mL to 20 mg/mL) constituted with Dextrose Injection 5% should be used immediately.
NOTE: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Adult Patients:
During clinical investigations, 2904 immunocompetent adult patients were treated for non-CNS infections with Meropenem for Injection (500 mg or 1 gram every 8 hours). Deaths in 5 patients were assessed as possibly related to meropenem; 36 (1.2%) patients had meropenem discontinued because of adverse events. Many patients in these trials were severely ill and had multiple background diseases, physiological impairments and were receiving multiple other drug therapies. In the seriously ill patient population, it was not possible to determine the relationship between observed adverse events and therapy with Meropenem for Injection
The following adverse reaction frequencies were derived from the clinical trials in the 2904 patients treated with Meropenem for Injection
Local Adverse Reactions
Local adverse reactions that were reported irrespective of the relationship to therapy with Meropenem for Injection were as follows:
| Inflammation at the injection site | 2.4% |
| Injection site reaction | 0.9% |
| Phlebitis/thrombophlebitis | 0.8% |
| Pain at the injection site | 0.4% |
| Edema at the injection site | 0.2% |
Systemic Adverse Reactions
Systemic adverse reactions that were reported irrespective of the relationship to Meropenem for Injection occurring in greater than 1.0% of the patients were diarrhea (4.8%), nausea/vomiting (3.6%), headache (2.3%), rash (1.9%), sepsis (1.6%), constipation (1.4%), apnea (1.3%), shock (1.2%), and pruritus (1.2%).
Additional systemic adverse reactions that were reported irrespective of relationship to therapy with Meropenem for Injection and occurring in less than or equal to 1.0% but greater than 0.1% of the patients are listed below within each body system in order of decreasing frequency:
Bleeding events were seen as follows: gastrointestinal hemorrhage (0.5%), melena (0.3%), epistaxis (0.2%), hemoperitoneum (0.2%), summing to 1.2%.
Body as a Whole: pain, abdominal pain, chest pain, fever, back pain, abdominal enlargement, chills, pelvic pain
Cardiovascular: heart failure, heart arrest, tachycardia, hypertension, myocardial infarction, pulmonary embolus, bradycardia, hypotension, syncope
Digestive System: oral moniliasis, anorexia, cholestatic jaundice/jaundice, flatulence, ileus, hepatic failure, dyspepsia, intestinal obstruction
Hemic/Lymphatic: anemia, hypochromic anemia, hypervolemia
Metabolic/Nutritional: peripheral edema, hypoxia
Nervous System: insomnia, agitation/delirium, confusion, dizziness, seizure, nervousness, paresthesia, hallucinations, somnolence, anxiety, depression, asthenia [see Warnings and Precautions (5.2) and (5.10)]
Respiratory: respiratory disorder, dyspnea, pleural effusion, asthma, cough increased, lung edema
Skin and Appendages: urticaria, sweating, skin ulcer
Urogenital System: dysuria, kidney failure, vaginal moniliasis, urinary incontinence
Adverse Laboratory Changes
Adverse laboratory changes that were reported irrespective of relationship to Meropenem for Injection and occurring in greater than 0.2% of the patients were as follows:
Hepatic: increased SGPT (ALT), SGOT (AST), alkaline phosphatase, LDH, and bilirubin
Hematologic: increased platelets, increased eosinophils, decreased platelets, decreased hemoglobin, decreased hematocrit, decreased WBC, shortened prothrombin time and shortened partial thromboplastin time, leukocytosis, hypokalemia
Renal: increased creatinine and increased BUN
NOTE: For patients with varying degrees of renal impairment, the incidence of heart failure, kidney failure, seizure and shock reported irrespective of relationship to Meropenem for Injection, increased in patients with moderately severe renal impairment (creatinine clearance greater than10 to 26 mL/min) [see Dosage and Administration (2.2), Warnings and Precautions (5.8), Use in Specific Populations (8.5) and (8.6) and Clinical Pharmacology (12.3)].
Urinalysis: presence of red blood cells
Complicated Skin and Skin Structure Infections
In a study of complicated skin and skin structure infections, the adverse reactions were similar to those listed above. The most common adverse events occurring in greater than5% of the patients were: headache (7.8%), nausea (7.8%), constipation (7.0%), diarrhea (7.0%), anemia (5.5%), and pain (5.1%). Adverse events with an incidence of greater than1%, and not listed above, include: pharyngitis, accidental injury, gastrointestinal disorder, hypoglycemia, peripheral vascular disorder, and pneumonia.
Pediatric Patients:
Clinical Adverse Reactions
Meropenem for Injection was studied in 515 pediatric patients (3 months to less than 13 years of age) with serious bacterial infections (excluding meningitis, see next section) at dosages of 10 mg/kg to 20 mg/kg every 8 hours. The types of clinical adverse events seen in these patients are similar to the adults, with the most common adverse events reported as possibly, probably, or definitely related to Meropenem for Injection and their rates of occurrence as follows:
| Diarrhea | 3.5% |
| Rash | 1.6% |
| Nausea and Vomiting | 0.8% |
Meropenem for Injection was studied in 321 pediatric patients (3 months to less than 17 years of age) with meningitis at a dosage of 40 mg/kg every 8 hours. The types of clinical adverse events seen in these patients are similar to the adults, with the most common adverse events reported as possibly, probably, or definitely related to Meropenem for Injection and their rates of occurrence as follows:
| Diarrhea | 4.7% |
| Rash (mostly diaper area moniliasis) | 3.1% |
| Oral Moniliasis | 1.9% |
| Glossitis | 1.0% |
In the meningitis studies, the rates of seizure activity during therapy were comparable between patients with no CNS abnormalities who received meropenem and those who received comparator agents (either cefotaxime or ceftriaxone). In the Meropenem for Injection treated group, 12/15 patients with seizures had late onset seizures (defined as occurring on day 3 or later) versus 7/20 in the comparator arm.
Meropenem for Injection was studied in 200 neonates and infants less than 3 months of age. The study was open-label, uncontrolled, 98% of the infants received concomitant medications, and the majority of adverse reactions were reported in neonates less than 32 weeks gestational age and critically ill at baseline, making it difficult to assess the relationship of the adverse reactions to Meropenem for Injection
The clinical adverse reactions seen in these patients that were reported (regardless of investigator assessment of causality) and their rates of occurrence are as follows:
| Convulsion | 5.0% |
| Hyperbilirubinemia (conjugated) | 4.5% |
| Vomiting | 2.5% |
Adverse Laboratory Changes
Laboratory changes seen in the pediatric studies, including the meningitis studies, were similar to those reported in the adult studies.
Skin and Skin Structure Infections
Use of Meropenem for Injection in pediatric patients 3 months of age and older with complicated skin and skin structure infections is supported by evidence from an adequate and well-controlled study in adults and additional data from pediatric pharmacokinetics studies [see Indications and Usage (1.3), Dosage and Administration (2.3), Adverse Reactions (6.1), Clinical Pharmacology (12.3) and Clinical Studies (14.1)].
Intra-abdominal Infections
Use of Meropenem for Injection in pediatric patients 3 months of age and older with intra-abdominal infections is supported by evidence from adequate and well-controlled studies in adults with additional data from pediatric pharmacokinetics studies and controlled clinical trials in pediatric patients. Use of Meropenem for Injection in pediatric patients less than 3 months of age with intra-abdominal infections is supported by evidence from adequate and well-controlled studies in adults with additional data from a pediatric pharmacokinetic and safety study [see Indications and Usage (1.2), Dosage and Administration (2.3), Adverse Reactions (6.1), Clinical Pharmacology (12.3) and Clinical Studies (14.2)].
Bacterial Meningitis
Use of Meropenem for Injection in pediatric patients 3 months of age and older with bacterial meningitis is supported by evidence from adequate and well-controlled studies in the pediatric population [see Indications and Usage (1.3), Dosage and Administration (2.3), Adverse Reactions (6.1), Clinical Pharmacology (12.3) and Clinical Studies (14.3)].
Plasma Concentrations
At the end of a 30-minute intravenous infusion of a single dose of Meropenem for Injection in healthy volunteers, mean peak plasma concentrations of meropenem are approximately 23 mcg/mL (range 14-26) for the 500 mg dose and 49 mcg/mL (range 39-58) for the 1 gram dose. A 5-minute intravenous bolus injection of Meropenem for Injection in healthy volunteers results in mean peak plasma concentrations of approximately 45 mcg/mL (range 18-65) for the 500 mg dose and 112 mcg/mL (range 83-140) for the 1 gram dose.
Following intravenous doses of 500 mg, mean plasma concentrations of meropenem usually decline to approximately 1 mcg/mL at 6 hours after administration.
No accumulation of meropenem in plasma was observed with regimens using 500 mg administered every 8 hours or 1 gram administered every 6 hours in healthy volunteers with normal renal function.
Distribution
The plasma protein binding of meropenem is approximately 2%.
Meropenem penetrates well into most body fluids and tissues including cerebrospinal fluid, achieving concentrations matching or exceeding those required to inhibit most susceptible bacteria. After a single intravenous dose of Meropenem for Injection, the highest mean concentrations of meropenem were found in tissues and fluids at 1 hour (0.5 hours to 1.5 hours) after the start of infusion, except where indicated in the tissues and fluids listed in the table below.
Table 1 Meropenem Concentrations in Selected Tissues (Highest Concentrations Reported)| Tissue | Intravenous. Dose
(gram) | Number of Samples | Mean [µg/mL or mcg/(gram)] at 1 hour unless otherwise noted | Range [µg/mL or mcg/(gram)] |
|---|
| Endometrium | 0.5 | 7 | 4.2 | 1.7–10.2 |
| Myometrium | 0.5 | 15 | 3.8 | 0.4–8.1 |
| Ovary | 0.5 | 8 | 2.8 | 0.8–4.8 |
| Cervix | 0.5 | 2 | 7 | 5.4–8.5 |
| Fallopian tube | 0.5 | 9 | 1.7 | 0.3-3.4 |
| Skin | 0.5 | 22 | 3.3 | 0.5–12.6 |
| Interstitial fluid obtained from blister fluid | 0.5 | 9 | 5.5 | 3.2-8.6 |
| Skin | 1 | 10 | 5.3 | 1.3–16.7 |
| Interstitial fluid | 1 | 5 | 26.3 | 20.9–37.4 |
| Colon | 1 | 2 | 2.6 | 2.5–2.7 |
| Bile | 1 | 7 | 14.6 (3 hours) | 4–25.7 |
| Gall bladder | 1 | 1 | — | 3.9 |
| Peritoneal fluid | 1 | 9 | 30.2 | 7.4–54.6 |
| Lung | 1 | 2 | 4.8 (2 hours) | 1.4–8.2 |
| Bronchial mucosa | 1 | 7 | 4.5 | 1.3–11.1 |
| Muscle | 1 | 2 | 6.1 (2 hours) | 5.3–6.9 |
| Fascia | 1 | 9 | 8.8 | 1.5–20 |
| Heart valves | 1 | 7 | 9.7 | 6.4–12.1 |
| Myocardium | 1 | 10 | 15.5 | 5.2–25.5 |
| CSF (inflamed) | 20 mg/kg in pediatric patients of age 5 months to 8 years
40 mg/kgin pediatric patients of age 1 month to 15 years | 8
5 | 1.1 (2 hours)
3.3 (3 hours) | 0.2-2.8
0.9-6.5 |
| CSF (uninflamed) | 1 | 4 | 0.2 (2 hours) | 0.1–0.3 |
Metabolism
There is one metabolite of meropenem that is microbiologically inactive.
Excretion
In subjects with normal renal function, the elimination half-life of meropenem is approximately 1 hour.
Meropenem is primarily excreted unchanged by the kidneys. Approximately 70% (50% – 75%) of the dose is excreted unchanged within 12 hours. A further 28% is recovered as the microbiologically inactive metabolite. Fecal elimination represents only approximately 2% of the dose. The measured renal clearance and the effect of probenecid show that meropenem undergoes both filtration and tubular secretion.
Urinary concentrations of meropenem in excess of 10 mcg/mL are maintained for up to 5 hours after a 500 mg dose.
Specific Populations
Renal Impairment
Pharmacokinetic studies with Meropenem for Injection in patients with renal impairment have shown that the plasma clearance of meropenem correlates with creatinine clearance. Dosage adjustments are necessary in subjects with renal impairment (creatinine clearance 50 mL/min or less) [see Dosage and Administration (2.2) and Use In Specific Populations (8.6)].
Meropenem I.V. is hemodialyzable. However, there is no information on the usefulness of hemodialysis to treat overdosage [see Overdosage (10)].
Hepatic Impairment
A pharmacokinetic study with Meropenem for Injection in patients with hepatic impairment has shown no effects of liver disease on the pharmacokinetics of meropenem.
Geriatric Patients
A pharmacokinetic study with Meropenem for Injection in elderly patients with renal impairment showed a reduction in plasma clearance of meropenem that correlates with age-associated reduction in creatinine clearance.
Pediatric Patients
The pharmacokinetics of Meropenem for Injection, in pediatric patients 2 years of age or older, are similar to those in adults. The elimination half-life for meropenem was approximately 1.5 hours in pediatric patients of age 3 months to 2 years.
The pharmacokinetics of meropenem in patients less than 3 months of age receiving combination antibacterial drug therapy are given below.
Table 2 Meropenem Pharmacokinetic Parameters in Patients Less Than 3 Months of AgeValues are derived from a population pharmacokinetic analysis of sparse data
| GA less than 32 weeks PNA less than 2 weeks (20mg/kg every 12 hours) | GA less than 32 weeks PNA 2 weeks or older (20mg/kg every 8 hours) | GA 32 weeks or older PNA less than 2 weeks (20mg/kg every 8 hours) | GA 32 weeks or older PNA 2 weeks or older (30mg/kg every 8 hours) | Overall |
|---|
| CL (L/h/kg) | 0.089 | 0.122 | 0.135 | 0.202 | 0.119 |
| V (L/kg) | 0.489 | 0.467 | 0.463 | 0.451 | 0.468 |
| AUC0-24 (mcg-h/mL) | 448 | 491 | 445 | 444 | 467 |
| Cmax (mcg/mL) | 44.3 | 46.5 | 44.9 | 61 | 46.9 |
| Cmin (mcg/mL) | 5.36 | 6.65 | 4.84 | 2.1 | 5.65 |
| T1/2 (h) | 3.82 | 2.68 | 2.33 | 1.58 | 2.68 |
Drug Interactions
Probenecid competes with meropenem for active tubular secretion and thus inhibits the renal excretion of meropenem. Following administration of probenecid with meropenem, the mean systemic exposure increased 56% and the mean elimination half-life increased 38%. Co-administration of probenecid with meropenem is not recommended.
Mechanism of Resistance
There are several mechanisms of resistance to carbapenems: 1) decreased permeability of the outer membrane of Gram- negative bacteria (due to diminished production of porins) causing reduced bacterial uptake, 2) reduced affinity of the target PBPs, 3) increased expression of efflux pump components, and 4) production of antibacterial drug-destroying enzymes (carbapenemases, metallo-β-lactamases). Localized clusters of infections due to carbapenem-resistant bacteria have been reported in some regions.
Cross-Resistance
Cross-resistance is sometimes observed with isolates resistant to other carbapenems.
Interactions with Other Antibacterial Drugs
In vitro tests show meropenem to act synergistically with aminoglycoside antibacterials against some isolates of Pseudomonas aeruginosa.
Spectrum of Activity
Meropenem has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section (1).
Gram-positive bacteria
Enterococcus faecalis (vancomycin-susceptible isolates only)
Staphylococcus aureus (methicillin-susceptible isolates only)
Streptococcus agalactiae
Streptococcus pneumoniae (penicillin-susceptible isolates only)
Streptococcus pyogenes
Viridans group streptococci
Gram-negative bacteria
Escherichia coli
Haemophilus influenzae
Klebsiella pneumoniae
Neisseria meningitidis
Pseudomonas aeruginosa
Proteus mirabilis
Anaerobic bacteria
Bacteroides fragilis
Bacteroides thetaiotaomicron
Peptostreptococcus species
The following in vitro data are available, but their clinical significance is unknown. At least 90% of the following bacteria have exhibited in vitro minimum inhibitory concentrations (MICs) less than or equal to the susceptible breakpoints for meropenem. However, the safety and effectiveness of meropenem in treating clinical infections due to these bacteria have not been established in adequate and well-controlled trials.
Gram-positive bacteria
Staphylococcus epidermidis (methicillin-susceptible isolates only)
Gram-negative bacteria
Aeromonas hydrophila
Campylobacter jejuni
Citrobacter koseri (formerly diversus)
Citrobacter freundii
Enterobacter cloacae
Hafnia alvei
Klebsiella oxytoca
Moraxella catarrhalis
Morganella morganii
Pasteurella multocida
Proteus vulgaris
Serratia marcescens
Anaerobic bacteria
Bacteroides distasonis
Bacteroides ovatus
Bacteroides uniformis
Bacteroides ureolyticus
Bacteroides vulgatus
Clostridium difficile
Clostridium perfringens
Eubacterium lentum
Fusobacterium species
Prevotella bivia
Prevotella intermedia
Prevotella melaninogenica
Porphyromonas asaccharolytica
Propionibacterium acnes
Susceptibility Test Methods
When available, the clinical microbiology laboratory should provide cumulative results of in vitro susceptibility test results for antimicrobial drugs used in local hospitals and practice areas to the physician as periodic reports that describe the susceptibility profile of nosocomial and community-acquired pathogens. These reports should aid the physician in selecting the most effective antimicrobial.
Dilution Techniques:
Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized test method. Standardized procedures are based on a dilution method1,3 (broth or agar) or equivalent using standardized inoculum concentrations and standardized concentrations of meropenem powder. The MIC values should be interpreted according to the criteria provided in Table 3.
Diffusion Techniques:
Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. The zone size provides an estimate of the susceptibility of bacteria to antimicrobial compounds. The zone size should be determined using a standardized test method 2,3 and requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 10-mcg of meropenem to test the susceptibility of microorganisms to meropenem. The disk diffusion interpretive criteria are provided in Table 3.
Anaerobic Techniques:
For anaerobic bacteria, the susceptibility to meropenem as MICs can be determined by a standardized test method.2,4 The MIC values obtained should be interpreted according to the criteria provided in Table 3.
Table 3 Susceptibility Interpretive Criteria for Meropenem | Minimum Inhibitory Concentrations (mcg/mL) | Disk Diffusion
(zone diameters in mm) |
|---|
| Pathogen | S | I | R | S | I | R |
|---|
| S = Susceptible, I = Intermediate, R = Resistant |
| No interpretative criteria have been established for testing enterococci. |
| Susceptibility of staphylococci to meropenem may be deduced from testing penicillin and either cefoxitin or oxacillin. |
| Enterobacteriaceae | ≤ 1 | 2 | ≥ 4 | ≥ 23 | 20-22 | ≤ 19 |
| Pseudomonas aeruginosa The interpretive criteria for P. aeruginosa are based upon the dosing of 1g every 8 hours. | ≤ 2 | 4 | ≥ 8 | ≥ 19 | 16-18 | ≤ 15 |
| Haemophilus influenzae The current absence of data on resistant isolates precludes defining any category other than "Susceptible". If isolates yield MIC results other than susceptible, they should be submitted to a reference laboratory for additional testing. | ≤ 0.5 | — | — | ≥ 20 | — | — |
| Neisseria meningitidis | ≤ 0.25 | — | — | ≥ 30 | — | — |
| Streptococcus pneumoniae For nonmeningitis isolates of S. pneumoniae a penicillin MIC of ≤ 0.06 mcg/mL or oxacillin zone ≥ 20 mm can predict susceptibility to meropenem. MIC testing should be performed on isolates that do not test as susceptible by either of these methods, and on all meningitis S. pneumoniae isolates. ,Reliable disk diffusion tests for meropenem do not yet exist for testing streptococci. | ≤ 0.25 | 0.5 | ≥ 1 | — | — | — |
| Streptococcus agalactiae and Streptococcus pyogenes, Viridans group streptococci should be tested for meropenem susceptibility using a MIC method and results should be reported using the interpretive criteria listed for S. agalactiae and S. pyogenes. , | ≤ 0.5 | — | — | — | — | — |
| Anaerobes MIC values using either Brucella blood or Wilkins Chalgren agar (former reference medium) are considered equivalent, based upon published in vitro literature and a multicenter collaborative trial for these antimicrobial agents. Broth microdilution is only recommended for testing the B. fragilis group. MIC values for agar or broth microdilution are considered equivalent for that group. | ≤ 4 | 8 | ≥ 16 | — | — | — |
A report of Susceptible indicates that the antimicrobial is likely to inhibit growth of the pathogen if the antimicrobial compound in the blood reaches the concentrations usually achievable. A report of Intermediate indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where a high dosage of drug can be used. This category also provides a buffer zone that prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of Resistant indicates that the antimicrobial is not likely to inhibit growth of the pathogen if the antimicrobial compound in the blood reaches the concentrations usually achievable; other therapy should be selected.
Quality Control
Standardized susceptibility test procedures require the use of quality controls to monitor and ensure the accuracy and precision of supplies and reagents used in the assay, and the techniques of the individuals performing the test. Standard meropenem powder should provide the following range of values noted in Table 4.
Table 4 Acceptable Quality Control Ranges for Meropenem| QC Strain | Minimum Inhibitory Concentrations
(MICs = mcg/mL) | Disk Diffusion
(Zone diameters in mm) |
|---|
Staphylococcus aureus
ATCC 29213 | 0.03-0.12 | — |
Staphylococcus aureus
ATCC 25923 | — | 29–37 |
Streptococcus pneumoniae
ATCC 49619 | 0.06-0.25 | 28–35 |
Enterococcus faecalis
ATCC 29212 | 2–8 | |
Escherichia coli
ATCC 25922 | 0.008-0.06 | 28–34 |
Haemophilus influenzae
ATCC 49766 | 0.03-0.12 | |
Haemophilus influenzae
ATCC 49247 | — | 20–28 |
Pseudomonas aeruginosa
ATCC 27853 | 0.25-1 | 27–33 |
| Bacteroides fragilis Using the Reference Agar Dilution procedure.
ATCC 25285 | 0.03–0.25 | |
Bacteroides thetaiotaomicron
ATCC 29741 | 0.125-0.5 | |
Eubacterium lentum
ATCC 43055 | 0.125-1 | |
Clostridium dificile
ATCC 700057 | 0.5-4 | |
