Imipenem indications

Beta-lactams such as cephaloridine, cephalothin, ce-fotiam and imipenem have been associated with nephrotoxicity in humans and experimental animals [9]. An understanding of their nephrotoxicity mechanisms may provide valuable information for elucidation of the biochemical mechanisms of newer P-Iactam nephrotoxicity. Similarly to cephaloridine, third- generation cephalosporins such as ceftazidime and cefsulodin and fourth-generation cephalosporins such as cefpirome and cefepime possess a quaternary nitrogen attached to the dihydrothiazine ring which may impart nephrotoxic potential [10]. Clinical and animal studies carried out with P-Iactams, such as cephaloglycin, cephaloridine, cephalothin or imipenem, indicated that they show a differential accumulation at the site of their toxicity, the renal cortex [11]. Elucidation of the mechanism of toxic action of these model (i-lactams has become the focus of several research efforts [12-16]. 

Erythromycin is considered the optimal drug for treatment of Campylobacter infections. The rate of resistance of Campylobacter to erythromycin remains low. Other advantages of this drug include ease of administration, low cost, lack of major toxicity, and narrow spectrum of activity.14 The recommended dosage for adults is 250 mg orally four times daily or 500 mg orally twice daily for 5 to 7 days. For very ill patients, treatment with gentamicin, imipenem, cefotaxime, or chloramphenicol is indicated, but susceptibility tests should be performed. 

Answer B (Amoxicillin). The multiple extractions can lead to bacteremia while the mitral valve stenosis and cardiac insufficiency place him at risk for developing endocarditis. The present American Heart Association guidelines indicate amoxicillin (3 gm 1 hour prior to procedure and 1.5 gm 6 hours after original dose.) Vancomycin would only be appropriate if the patient was allergic to penicillins. Tetracycline and cotrimoxazole are bacteriostatic and not effective against the viridans group of Streptococci, the usual causative organism. Imipenem is also inappropriate since its spectrum is too broad. 

Combination therapy is often used when dealing with infections caused by both aerobic and anaerobic bacteria [50,80]. Combination of metronidazole with either gentamicin or ciprofloxacin appeared to be effective in preventing infection of abdominal trauma [101] when combined with ciprofloxacin, metronidazole was affective as a preoperative antibiotic in colorectal surgery and appeared equal in efficacy to impipenem/cilastin for the treatment of complicated intraabdominal infections [103]. Combination therapy is not always indicated for the treatment of polymicrobial infections. New antibiotics, whose spectrum includes multiple classes of microorganisms (e.g., imipenem), may often preclude combination therapy. 

For a less supersaturated solution, Fig. 2-12 indicates that the amorphous solid can be generated after aging of the oil droplets. An amorphous solid can also be formed by rapid cooling of a saturated solution, as in lyophilization or freeze-drying operations. Like oil droplets, amorphous solids are unstable and will transform into crystalline material upon aging under proper conditions. As shown in Example 12-5, the amorphous imipenem can be transformed into crystalline material even under freezing conditions. 

Figures 11-14 to 11-17 show the differential scanning calorimetry (DSC) thermograph of the acetone/ water solvent mixture with and without the presence of imipenem. The DSC curves indicate endothermic peaks which correspond to the phase transitions. The peaks around O C and —95°C represent the melting of the solid water and acetone phases, respectively. The peaks around — 19°C represent the melting of the solid clathrate phase (Rosso et al. 1975). The clathrate is a solid phase complex of 17 water molecules surrounding a single molecule of acetone, niLDOCllOrCO. In addition, the DSC thermograms indicate only slight temperature flucUiations for the endotherms with the addition of imipenem and the sodium bicarbonate. Therefore, the acetone/water binary phase behavior is not affected significantly by the addition of imipenem and sodium bicarbonate.

The solubility values for imipenem in the 30% acetone/water solution are 0.72, 0.40, and 0.22 gm/liter at —10°C, — 20°C, and —30°C, respectively. Values for solubilities in the equilibrium solutions at -20°C and -30 C could not be measured. These solubility results indicate that imipenem is slightly soluble in the liquid phases present at equilibrium under the freeze crystallization conditions. Therefore, it may be assumed that the transition from amorphous form to crystalline form is facilitated by the presence of a liquid phase. 

Unfortunately, MAC is resistant to the standard drugs used for tuberculosis, such as isoniazid and pyrazinamide. Multiple agents such as rifampin, rifabutin (ansamycin), clofazimine, imipenem, amikacin, ethambutol, ciprofloxacin, clarithromycin, and azithromycin have varying degrees of in vitro anti-MAC activity. Controversy formerly existed as to whether treatment for MAC is beneficial, but data indicate that an aggressive therapeutic approach decreases symptoms... 

Imipenem inhibits bacterial cell wall synthesis. Cilastatin prevents metabolism of imipenem, resulting in increased urinary recovery and decreased renal toxicity. They are indicated in the treatment of serious infections of the lower respiratory tract and urinary tract, intra-abdominal and gynecologic infections, bacterial septicemia, bone and joint infections, skin and skin structure infections, endocarditis, and polymicrobic infections due to susceptible microorganisms. 

Imipenem, a carbapanem (thienamycin class), beta-lactam antibiotic (750 mg IM q. 12 hours), is indicated in mild to moderate lower respiratory tract, skin and skin-structme, or gynecologic infections mild-to-moderate intra-abdominal infections in serious respiratory and urinary tract infections intra-abdominal, gynecologic, bone, joint, or skin infections bacterial septicemia or endocarditis. 

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