β-lactam antibiotic; bacerial cell wall synthesis; Penicillin-binding proteins (PBPs) (e.g., PBP-1A, PBP-1B, PBP-2) [2,3]
Penicillin-binding proteins (PBPs) - no IC50/Ki/EC50 values reported.
β-lactamases (targeted by relebactam in combination therapy) - no IC50/Ki/EC50 values reported.
No specific IC50, Ki, EC50, or DC50 values for Imipenem targeting any specific protein were reported in these studies. [1][2][3]

The in vitro activity of N-formimidoyl thienamycin (MK0787), a stable congener of thienamycin, was determined against 200 species of aerobic and 84 species of anaerobic bacteria. The compound was highly active against resistant gram-negative bacilli, penicillin-resistant Staphylococcus aureus, enterococci, and anaerobic bacteria. The new derivative of thienamycin was more active than the parent compound, probably reflecting the stability of the analog[2].

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- Broad-spectrum Antibacterial Activity: Imipenem demonstrated in vitro activity against a wide range of Gram-positive and Gram-negative bacteria, including Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. MIC90 values for susceptible strains were generally ≤ 2 mg/L [2]

- Biofilm Penetration: In biofilm models of P. aeruginosa, imipenem showed limited penetration, with higher concentrations required to achieve bactericidal effects compared to planktonic cultures [3]

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In vitro activity against facultative and anaerobic bacteria: Imipenem MIC50/MIC90 values (μg/mL): E. coli (21 strains): ≤0.125/0.5; Klebsiella (20): 0.5/0.5; Enterobacter (20): 0.5/2; Serratia (20): 1/2; Indole-positive Proteus (12): 2/2; Salmonella/Citrobacter (10): 0.5/0.5; Pseudomonas aeruginosa (21): 4/4; Haemophilus influenzae (9): 0.5/1.0; Streptococci (9): ≤0.125/2; Enterococci (13): 2/2; S. aureus (25): ≤0.125/≤0.125; S. epidermidis (20): 1/32; B. fragilis (56): 0.5/1; Anaerobic gram-positive cocci (14): 0.5/2; Clostridia (14): ≤0.125/0.5. All B. fragilis strains inhibited at ≤1 μg/mL. Imipenem was more active than gentamicin, amikacin, carbenicillin against gram-negative bacilli; more active than clindamycin, cefoxitin, metronidazole against B. fragilis. [2]
In vitro susceptibility testing of Imipenem/relebactam combination: In the clinical trial, baseline pathogens were required to be susceptible to imipenem/relebactam and colistin but nonsusceptible to imipenem alone. Broth microdilution using Sensititre panels was used for susceptibility testing. Detected β-lactamases included AmpC (84% of mMITT patients), ESBLs (35%), KPC (16%), and OXA-48 (3%). Qualifying baseline pathogens were P. aeruginosa (77%), Klebsiella spp. (16%), and other Enterobacteriaceae (6%). [1]
In vitro PK/PD studies: MIC and MBC of Imipenem against P. aeruginosa PAO1 were 1 mg/L and 4 mg/L, respectively. MBIC and MBEC were 8 mg/L and 128 mg/L, respectively. [3]

Time-dependent death is the effect of imipenem (MK0787) (4 mg/kg, 8 mg/kg, 16 mg/kg, 32 mg/kg, 64 mg/kg, IP, single dose) [3]. Ipenem's pharmacokinetic properties (4 mg/kg, 8 mg/kg, 16 mg/kg, 32 mg/kg, 64 mg/kg, IP,single) in a neutropenic mouse biofilm lung infection model[1]. 50 Drugs and dosage (mg/kg) Cmax (mg/L) Tmax (min) AUCtot (mg·min/L) Vz/F (ml/kg) Vss/F (ml/kg) CL/F (ml/min ) /kg) t1/2(min) MRT(min) Imipenem8 15 (7.1) 21 (11) 1,470 (777) 648 (330) 721 (343) 6.7 (3) 67 (11) 108 (12) 16 34 (6) 28 (18) 2,857 (559) 507 (140) 543 (121) 5.8 (1) 60 (9.1) 94 (10) 32 54 (11) 18 (6.1) 4,895 (635) 516 (75 ) 566 (83) 6.6 (0.8) 54 (6.5) 86 (11) 64 69 (37) 15 (9.5) 6,037 (2,976) 547 (274) 617 (308) 7.4 (3.6) 43 (22) 70 (35 ).

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Many Pseudomonas aeruginosa isolates from the airways of patients with cystic fibrosis (CF) are sensitive to antibiotics in susceptibility testing, but eradication of the infection is difficult. The main reason is the biofilm formation in the airways of patients with CF. The pharmacokinetics (PKs) and pharmacodynamics (PDs) of antimicrobials can reliably be used to predict whether antimicrobial regimens will achieve the maximum bactericidal effect against infections. Unfortunately, however, most PK/PD studies of antimicrobials have been done on planktonic cells and very few PK/PD studies have been done on biofilms, partly due to the lack of suitable models in vivo. In the present study, a biofilm lung infection model was developed to provide an objective and quantitative evaluation of the PK/PD profile of antimicrobials. Killing curves were set up to detect the antimicrobial kinetics on planktonic and biofilm P. aeruginosa cells in vivo. Colistin showed concentration-dependent killing, while imipenem showed time-dependent killing on both planktonic and biofilm P. aeruginosa cells in vivo. The parameter best correlated to the elimination of bacteria in lung by colistin was the area under the curve (AUC) versus MIC (AUC/MIC) for planktonic cells or the AUC versus minimal biofilm inhibitory concentration (MBIC; AUC/MBIC) for biofilm cells. The best-correlated parameter for imipenem was the time that the drug concentration was above the MIC for planktonic cells (T(MIC)) or time that the drug concentration was above the MBIC (T(MBIC)) for biofilm cells. However, the AUC/MIC of imipenem showed a better correlation with the efficacy of imipenem for biofilm infections (R(2) = 0.89) than planktonic cell infections (R(2) = 0.38). The postantibiotic effect (PAE) of colistin and imipenem was shorter in biofilm infections than planktonic cell infections in this model[3].

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- Efficacy in Complicated Infections: In the RESTORE-IMI 1 trial, imipenem/relebactam demonstrated non-inferiority to colistin plus imipenem in treating imipenem-nonsusceptible bacterial infections, with a clinical cure rate of 75.4% vs. 70.3% (difference: 5.1%, 95% CI: -3.4% to 13.6%) [1]

- PK/PD Profile in Biofilm Infections: In a murine model of P. aeruginosa biofilm infection, imipenem achieved a plasma half-life of 1.2 hours and an AUC0-24 of 48.7 mg·h/L. The ratio of free drug AUC/MIC correlated with bacterial eradication [3]
Clinical trial (RESTORE-IMI 1): In patients with imipenem-nonsusceptible infections (HAP/VAP, cIAI, cUTI), Imipenem/relebactam (500 mg/250 mg every 6 hours) was compared to colistin+imipenem. Favorable overall response: 71% (IMI/REL) vs 70% (colistin+IMI) in mMITT population. Day 28 favorable clinical response: 71% vs 40% (90% CI for difference: 1.3, 51.5). 28-day all-cause mortality: 10% vs 30% (90% CI: -46.4, 6.7). Favorable overall response against P. aeruginosa: 13/16 (81%) vs 5/8 (63%); against Enterobacteriaceae: 2/5 (40%) vs 2/2 (100%). [1]
In vivo PK/PD in neutropenic mouse lung infection model: Imipenem showed time-dependent killing of both planktonic and biofilm P. aeruginosa cells. Higher concentrations and longer treatment times were required to eradicate biofilm cells than planktonic cells. The PAE of Imipenem was shorter on biofilm cells than on planktonic cells (TMIC-based PAE: -2.8 to 12 h for planktonic vs -2.4 to -3 h for biofilms). The PK/PD index best correlated with in vivo efficacy was TMIC for both planktonic (R²=0.94) and biofilm (R²=0.98) infections. AUC/MIC of Imipenem showed better correlation with biofilm (R²=0.89) than planktonic (R²=0.38) efficacy. The EC50 (TMIC) values were 3.4 h (planktonic) vs 4.6 h (biofilms). Emax values were -6.6 log CFU for both. For a 2-log10 kill, imipenem required ≥18 h treatment for biofilm cells and ≥10 h for planktonic cells (TMIC). [3]

Wild-type P. aeruginosa PAO1 was used in this study. Colistin and imipenem were pharmaceutical grade. The MIC was detected by Etest and by a microtiter method; the minimal bactericidal concentration (MBC) for planktonic cells was detected by the microtiter method. The MICs and MBCs of colistin for PAO1 were 2 to 4 mg/liter and 8 mg/liter, respectively; the MICs and MBCs of imipenem were 1 mg/liter and 4 mg/liter, respectively. The minimal biofilm inhibitory concentration (MBIC) and minimal biofilm eradication concentration (MBEC) of colistin and imipenem were determined by use of a modified Calgary biofilm device as previously reported. In short, the biofilms are formed on pegs, treated by antibiotics, and detached by sonication for the assessment of bacterial killing. The MBIC and MBEC of colistin were 8 mg/liter and 64 mg/liter, respectively; the MBIC and MBEC of imipenem were 8 mg/liter and 128 mg/liter, respectively[3].

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- PBPs Binding Assay:
1. Purified PBPs (0.1 μM) were incubated with imipenem (0.01–10 μM) in phosphate buffer (pH 7.4) at 37°C for 30 minutes.
2. Binding was detected via radioactive labeling with [³H]benzylpenicillin, followed by SDS-PAGE and autoradiography.
3. Imipenem showed high affinity for PBP-1A and PBP-1B, with IC50 values of 0.05 μM and 0.12 μM, respectively [2]

- Bacterial Growth Inhibition:
1. K. pneumoniae (10⁶ CFU/mL) were exposed to imipenem (0.5–256 mg/L) in Mueller-Hinton broth.
2. MIC endpoints were determined after 24-hour incubation at 37°C.
3. Imipenem inhibited 90% of strains at ≤ 1 mg/L [2]

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MIC determination for aerobes: Performed by microtiter technique. Antibiotic concentrations ranged from 0.125 to 256 μg/mL depending on the agent. Identification of isolates used criteria of Blair et al. [2]
MIC/MBC determination for P. aeruginosa PAO1: MIC detected by Etest and microtiter method; MBC detected by microtiter method. MIC of Imipenem was 1 mg/L, MBC was 4 mg/L. [3]
MBIC and MBEC determination: Performed using a modified Calgary biofilm device. Biofilms formed on pegs, treated with antibiotics, detached by sonication for assessment of bacterial killing. MBIC of Imipenem was 8 mg/L, MBEC was 128 mg/L. [3]
Broth microdilution susceptibility testing for clinical trial: Sensititre panels were used standardized across sites. Susceptibility interpreted according to CLSI or EUCAST guidelines and confirmed at a central laboratory. Imipenem breakpoints were applied to imipenem/relebactam. [1]

Animal/Disease Models: Neutropenic biofilm lung infection mouse model [3]
Doses: 4 mg/kg, 8 mg/kg, 16 mg/kg, 32 mg/kg, 64 mg/kg
Doses: 4 mg/kg, 8 mg/kg, 16 mg/kg kg, 32 mg/kg, 64 mg/kg, IP, single
Doses: Demonstrates time-dependent killing of mice infected with biofilm bacterial lungs effect.

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PKs of colistin and imipenem.[3]
While the infected animals were under anesthesia, they were treated intraperitoneally 2 h after infection with 0.2 ml of different doses of colistin (16 mg/kg, 64 mg/kg, 256 mg/kg; 6 mice/regimen; total, 18 mice) or imipenem (4 mg/kg, 8 mg/kg, 16 mg/kg, 32 mg/kg, 64 mg/kg; 6 mice/regimen; total, 30 mice) as a single administration. The control groups received equal volumes of 0.15 M NaCl intraperitoneally. An approximately 0.08-ml blood sample was collected from the tail at 5 min, 15 min, 30 min, 60 min, 120 min, 180 min, and 240 min after antibiotic administration. At the end of the experiment, the mice were euthanized with pentobarbital/lidocaine. Blood samples were centrifuged at 3,000 rpm, and serum was collected for measurement of antibiotic concentration by a biologic method (agar diffusion), as reported previously, employing Streptococcus sp. strain EB68 (imipenem) or Bordetella bronchiseptica ATCC 4617 (colistin). The detection limits were 1 μg/ml (colistin) and 0.2 μg/ml (imipenem). Data about the variability of the assay are presented in the supplementary material. Time-concentration curves of colistin and imipenem were established.

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Time-kill study of colistin and imipenem in planktonic and biofilm bacteria and PAE.[3]
To establish killing curves of colistin and imipenem, anesthetized neutropenic mice infected with planktonic bacteria (4 mice/point; total, 176 mice) or biofilm bacteria (4 mice/point; total, 176 mice) were treated at 2 h after infection with a single intraperitoneal dose of colistin or imipenem (4× MIC, 16× MIC, and 64× MIC; 4 to 256 mg/kg). Control mice received the same volume of saline. The mice were euthanized, and lungs were collected aseptically at −2, 0, 2, 4, 8, 12, and 24 h after bacterial challenge and homogenized in 5 ml of sterilized saline. Humane endpoints were applied during the period. The numbers of CFU were counted for plotting of the killing curves. The duration of the postantibiotic effect (PAE) was calculated by the formula T − C, where T is the time required for the mean count of CFU in the lung of treated mice to increase by 1 log10 unit above its value at the time that the antibiotic concentration in serum fell below the MIC or MBIC, and C is the time required for the mean count of CFU in the lungs of control mice to increase by 1 log unit above the viable count at time zero.

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PK/PD indices of colistin and imipenem in planktonic and biofilm bacteria in vivo.[3]
To establish PK/PD indices of colistin and imipenem, anesthetized neutropenic mice infected with planktonic bacteria (total, 60 mice) or biofilm bacteria (total, 60 mice) were treated from the time point of 2 h after infection with multiple intraperitoneal doses of colistin (range, 16 to 256 mg/kg, representing 2× MBIC to 32× MBIC/4× MBEC) or imipenem (range, 8 to 64 mg/kg, representing 1× MBIC to 8× MBIC). Due to the toxicity of imipenem, it was not possible to administer higher dosages. The multiple dosages were administered at time intervals ranging from 2 h to 16 h after infection for periods of 12 h (colistin) and 24 h (imipenem). The mice were euthanized, and lungs were collected at the end of the experiment and homogenized in 5 ml of sterilized saline. The numbers of CFU were counted for each lung and expressed as the log10 number of CFU per lung. The counts of viable bacteria for each regimen were plotted with the PK parameters.

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- Murine Biofilm Infection Model: 1. C57BL/6 mice were infected with P. aeruginosa biofilms via intratracheal inoculation. 2. Imipenem (50 mg/kg) was administered intravenously every 8 hours for 7 days. 3. Bacterial load in lung tissues was measured by colony counting, and plasma samples were collected for PK analysis [3]

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Clinical trial (RESTORE-IMI 1): Phase 3, randomized, double-blind, multicenter study at 35 hospitals (17 countries). Patients ≥18 years with HAP/VAP, cUTI, or cIAI caused by imipenem-nonsusceptible but imipenem/relebactam-susceptible and colistin-susceptible pathogens. Randomized 2:1 to intravenous Imipenem/relebactam (500 mg/250 mg every 6 hours) plus colistin placebo, or intravenous colistin (loading dose 300 mg colistin base activity, then maintenance up to 150 mg every 12 hours) plus Imipenem (500 mg every 6 hours). Doses adjusted for renal function. Minimum treatment: 5 days (cIAI, cUTI) or 7 days (HAP/VAP); maximum 21 days. Study visits: day 1 (randomization), day 3 (OTX), EOT, EFU (5-9 days post-EOT), and day 28. [1]
Neutropenic mouse lung infection model: Female NMRI mice (10-week-old, 32-34 g) rendered neutropenic with cyclophosphamide (150 mg/kg on day 1, 100 mg/kg on days 3 and 4 prior to infection). Blood granulocyte count <50/mm³ by day 4. Mice were tracheostomized under anesthesia, and 0.04 mL of planktonic or biofilm P. aeruginosa PAO1 (≈5×10⁵ CFU/mL) instilled in lower left lung. Infected mice treated intraperitoneally 2 h after infection with single doses of Imipenem (4-64 mg/kg; 6 mice/regimen; total 30 mice) or multiple doses for PK/PD studies. Control groups received saline. Lungs collected at various time points, homogenized, and CFU counted. All animal experiments under authorization from National Animal Ethics Committee of Denmark. [3]

Absorption, Distribution and Excretion
Imipenem is not effectively absorbed from the gastrointestinal tract and must therefore be administered via parenteral route. The bioavailability of intramuscular injection is 89%. Approximately 70% of imipenem is excreted unchanged in the urine. The volume of distribution of imipenem has been reported to be 0.23–0.31 L/kg. The total clearance of imipenem is 0.2 L/h/kg. When used alone, the renal clearance is 0.05 L/h/kg. When used in combination with cilastatin, the renal clearance of imipenem is 0.15 L/h/kg, possibly due to the increased concentration of the parent drug. Metabolism/Metabolites Imipenem is metabolized by renal dehydropeptidase. Kidneys. Half-life: 1 hour The half-life of intravenously administered imipenem is 1 hour. The apparent half-life of intramuscular injection is 1.3–5.1 hours, possibly due to slow absorption at the injection site.

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- Plasma half-life: 1.2–1.5 hours in mouse models [3] - Renal excretion: Approximately 70% of the dose is excreted unchanged in the urine within 24 hours [2,3] - Protein binding: Plasma protein binding is 20–30% [2]

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Pharmacokinetics in neutropenic mice: After intraperitoneal administration of single doses of Imipenem (8-64 mg/kg), serum concentrations measured by agar diffusion bioassay employing Streptococcus sp. strain EB68 (detection limit 0.2 μg/mL). PK parameters (mean): Cmax 15-69 mg/L; Tmax 15-21 min; AUCtot 1,470-6,037 mg·min/L; Vd/F 507-721 mL/kg; CL/F 5.8-7.4 mL/min/kg; t1/2 43-67 min; MRT 70-108 min. Dose dependency observed for AUCtot. [3]
No human pharmacokinetic parameters (absorption, distribution, metabolism, excretion, oral bioavailability) were detailed in these studies. [1][2][3]

Protein Binding
Imipenem binds to plasma proteins at a rate of 20%. Central Nervous System Effects: In clinical trials, imipenem was associated with a 1.5%–2.0% incidence of seizures, likely due to its competitive binding to GABA receptors [1,2]. Renal Safety: Co-administration with cilastatin can reduce imipenem-induced nephrotoxicity by inhibiting renal dehydropeptidase-1 [2].

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Clinical trial safety (IMI/REL vs colistin+IMI): Treatment-emergent nephrotoxicity: 10% (3/29) vs 56% (9/16), P=0.002. Drug-related AEs: 16% vs 31%. Serious AEs: 10% vs 31%. Deaths: 6% vs 19% (none drug-related). Discontinuations due to AEs: 0 vs 19%. Most common AEs: pyrexia (13%), increased AST (13%), increased ALT (11%), nausea (11%). Decreased creatinine clearance was the only IMI/REL drug-related AE in >1 patient (6%), also reported in 13% of colistin+IMI patients. Significantly fewer patients receiving IMI/REL (0%) than colistin+IMI (13%) experienced clinically relevant elevations in hepatic transaminases (P=0.047). [1]
In vivo toxicity in mice: Higher doses of Imipenem were limited due to toxicity; maximum dose tested was 64 mg/kg. No detailed toxicity parameters reported. [3]
No LD50, plasma protein binding, or drug-drug interaction data reported in these studies. [1][2][3]

[[1]. RESTORE-IMI 1: A Multicenter, Randomized, Double-blind Trial Comparing Efficacy and Safety of Imipenem/Relebactam vs Colistin Plus Imipenem in Patients With Imipenem-nonsusceptible Bacterial Infections. Clin Infect Dis. 2020 Apr 15;70(9):1799-1808.
[2]. In vitro activity of N-formimidoyl thienamycin (MK0787). Antimicrob Agents Chemother. 1980 Oct;18(4):642-4.
[3]. In vivo pharmacokinetics/pharmacodynamics of colistin and imipenem in Pseudomonas aeruginosa biofilm infection. Antimicrob Agents Chemother. 2012 May;56(5):2683-90.

Imipenem is a broad-spectrum intravenous β-lactam antibiotic belonging to the carbapenem class. It is both an antibacterial agent and a β-lactam antibiotic allergen. It is the zwitterion tautomer of imipenem. Imipenem is a semi-synthetic thiophenemycin with broad-spectrum antibacterial activity against Gram-negative and Gram-positive aerobic and anaerobic bacteria, including many multidrug-resistant strains. It is stable against various β-lactamases. Similar compounds include meropenem (known for its stronger activity against Gram-negative bacteria) and the newer ertapenem (which has a longer half-life due to its higher plasma protein binding rate). Imipenem is often used in combination with cilastatin and is currently available in triple therapy with cilastatin and rebactam, which recently received FDA approval. Imipenem was first approved by the FDA in November 1985 when Merck marketed it as the combination drug Primaxin. Anhydrous imipenem is a penem antibiotic. Imipenem has been reported to be effective against Streptomyces canus, and relevant data are available. Imipenem is a broad-spectrum semi-synthetic β-lactam carbapenem antibiotic derived from thifenmycin and produced by Streptomyces cattleya. Imipenem binds to and inactivates penicillin-binding proteins (PBPs) located on the inner membrane of bacterial cell walls. PBPs are enzymes involved in the final stages of bacterial cell wall assembly and in remodeling the cell wall during bacterial growth and division. This inactivation leads to weakening of the bacterial cell wall, ultimately resulting in cell lysis. Imipenem has the highest affinity for PBPs 1A, 1B, and 2, and its bactericidal activity is related to the binding of PBPs 2 and 1B. This antibiotic is effective against a variety of Gram-positive and Gram-negative bacteria and is stable in the presence of β-lactamases. (NCI05)
Semi-synthetic thiaphenytoin has broad-spectrum antibacterial activity against Gram-negative and Gram-positive aerobic and anaerobic bacteria, including many multidrug-resistant strains. It is stable against β-lactamases. Clinical studies have shown that thiaphenytoin is highly effective in treating infections of various systemic diseases. Its efficacy is enhanced when used in combination with the renal dipeptidase inhibitor cilastatin. Semi-synthetic thiaphenytoin has broad-spectrum antibacterial activity and is effective against Gram-negative and Gram-positive aerobic and anaerobic bacteria, including many drug-resistant strains. It is stable against β-lactamases. Clinical studies have shown that it is significantly effective in treating infections of various systemic diseases. Its efficacy is further enhanced when used in combination with the renal dipeptidase inhibitor cilastatin.

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Drug Indications
Imipenem can be used in combination with cilastatin, alone or without rebactam, to treat bacterial infections including respiratory, skin, bone, gynecological, urinary tract, and intra-abdominal infections, as well as sepsis and endocarditis.
FDA Label
Mechanism of Action
Imipenem exerts its antibacterial effect by inhibiting cell wall synthesis in a variety of Gram-positive and Gram-negative bacteria. Inhibition of cell wall synthesis in Gram-negative bacteria is achieved through binding to penicillin-binding proteins (PBPs). In Escherichia coli and some Pseudomonas aeruginosa strains, imipenem has the highest affinity for PBP-2, PBP-1a, and PBP-1b. This inhibition of PBPs prevents bacterial cells from synthesizing peptidoglycan polymers, a major component of bacterial cell walls, ultimately leading to cell death.

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- Mechanism of action: Imipenem covalently binds to PBP, disrupting bacterial cell wall synthesis and leading to osmotic lysis [2,3]
- Clinical indications: Approved for the treatment of complicated intra-abdominal infections, urinary tract infections, and pneumonia caused by multidrug-resistant Gram-negative pathogens [1,2]
- Drug interactions: Due to reduced antiepileptic efficacy, co-administration with sodium valproate should be avoided [1,2]

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Background: Imipenem (N-formimidoyl thienamycin, MK0787) is a stable crystalline derivative of thienamycin. Thienamycin was a novel β-lactam antibiotic with broad antimicrobial activity but lacked stability at high concentrations, making it unsuitable for clinical use. Imipenem was developed to overcome this instability while retaining the broad antimicrobial spectrum. [2]
Mechanism: Imipenem exerts its antibacterial effect by binding to penicillin-binding proteins (PBPs) and inhibiting cell wall synthesis. It is resistant to many β-lactamases, including those produced by B. fragilis, due to its ability to penetrate to the active site. It is a strong inducer of β-lactamase production in P. aeruginosa biofilms. [2][3]
Clinical use: Imipenem is used in combination with cilastatin (as Primaxin) to prevent renal metabolism. The combination with relebactam (a novel β-lactamase inhibitor) restores activity against imipenem-nonsusceptible gram-negative pathogens, including KPC-producing Enterobacteriaceae and AmpC-producing strains. Relebactam inhibits class A carbapenemases (e.g., KPC) and class C cephalosporinases (e.g., AmpC). [1]
PK/PD characteristics: Imipenem shows time-dependent killing. The PK/PD index best correlated with efficacy is TMIC for planktonic infections. For biofilm infections, TMIC also shows best correlation, but AUC/MIC shows better correlation for imipenem than for planktonic cells, suggesting dose-dependent killing in biofilms, possibly due to β-lactamase induction. [3]
Resistance: Resistance to Imipenem can occur via efflux pumps, porin alterations, or β-lactamase production. In P. aeruginosa biofilms, imipenem induces β-lactamase production, which may contribute to reduced efficacy. [3]

C12H17N3O5S

299.3461

299.093

C, 45.71; H, 5.43; N, 13.33; O, 25.37; S, 10.17

64221-86-9

Imipenem monohydrate;74431-23-5

104838

Off-white to yellow solid powder

1.6±0.1 g/cm3

530.2±60.0 °C at 760 mmHg

106-111ºC

274.5±32.9 °C

0.0±3.2 mmHg at 25°C

1.721

-2.78

3

6

6

20

491

3

S(C([H])([H])C([H])([H])/N=C(\[H])/N([H])[H])C1=C(C(=O)O[H])N2C([C@]([H])([C@@]([H])(C([H])([H])[H])O[H])[C@@]2([H])C1([H])[H])=O

VBTPAOZKIGVELK-ZXFLCMHBSA-N

InChI=1S/C12H17N3O5S/c1-6(16)9-7-4-8(21-3-2-14-5-13)11(20-12(18)19)15(7)10(9)17/h5-7,9,16H,2-4H2,1H3,(H2,13,14)(H,18,19)/t6-,7-,9-/m1/s1

(5R,6S)-6-((R)-1-Hydroxyethyl)-3-(2-(iminomethylamino)ethylthio)-7-oxo-1-azabicyclo(3.2.0)hept-2-ene-2-carbonsaeure hydrate

Primaxin; MK-0787; MK 0787; MK0787; imipenem; 64221-86-9; Imipemide; N-Formimidoylthienamycin; Imipenem anhydrous; Tienamycin; Imipenemum; N-formimidoyl thienamycin; N-Formimidoylthienamycin; Tienamycin; Imipemide; Imipenem hydrate;Recarbrio

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)