bacteria. when culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. in the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. indications

erial agents, including penicillin g, and may range in severity from mild to life-threatening. therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents. treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. studies indicate that a toxin produced by clostridium difficile is one primary cause of “antibiotic-associated colitis”. after the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. in moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation and treatment with an antibacterial drug effective against c. difficile.

d renal impairment. for most acute infections, treatment should be continued for at least 48 to 72 hours after the patient becomes asymptomatic. antibiotic therapy for group a β-hemolytic streptococcal infections should be maintained for at least 10 days to reduce the risk of rheumatic fever. parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. preparation of solution solutions of penicillin should be prepared as follows: loosen powder. hold vial horizontally and rotate it while slowly directing the stream of diluent against the wall of the vial. shake vial vigorously after all the diluent has been added. depending on the route of administration, use sterile water for injection, usp or sterile isotonic sodium chloride solution for parenteral use. note: penicillins are rapidly inactivated in the presence of carbohydrate solutions at alkaline ph. reconstitution the following table shows the amount of solvent required for solution of various concentrations: when the required volume of solvent is greater than the capacity of the vial, the penicillin can be dissolved by first injecting only a portion of the solvent into the vial, then withdrawing the resultant solution and combining it with the remainder of the solvent in a larger sterile container. penicillin g potassium for injection, usp is highly water soluble. it may be dissolved in small amounts of water for injection, or sterile isotonic sodium chloride solution for parenteral use. all solutions should be stored in a refrigerator. when refrigerated, penicillin solutions may be stored for seven days without significant loss of potency. buffered penicillin g potassium for injection may be given intramuscularly or by continuous intravenous drip for dosages of 500,000, 1,000,000 or 5,000,000 units. it is also suitable for intrapleural, intraarticular, and other local installations. the 20,000,000 unit (20 million unit) dosage may be administered by intravenous infusion only. (1) intramuscular injection: keep total volume of injection small. the intramuscular route is the preferred route of administration. solutions containing up to 100,000 units of penicillin per ml of diluent may be used with a minimum of discomfort. greater concentration of penicillin g per ml is physically possible and may be employed where therapy demands. when large doses are required, it may be advisable to administer aqueous solutions of penicillin by means of continuous intravenous drip. (2) continuous intravenous drip: determine the volume of fluid and rate of its administration required by the patient in a 24-hour period in the usual manner for fluid therapy, and add the appropriate daily dosage of penicillin to this fluid. for example, if an adult patient requires 2 liters of fluid in 24 hours and a daily dosage of 10 million units of penicillin, add 5 million units of 1 liter and adjust the rate of flow so the liter will be infused in 12 hours. (3) intrapleural or other local infusion: if fluid is aspirated, give infusion in a volume equal to 1/4 or 1/2 the amount of fluid aspirated, otherwise, prepare as for an intramuscular injection. (4) intrathecal use: the intrathecal use of penicillin in meningitis must be highly individualized. it should be employed only with full consideration of the possible irritating effects of penicillin when used by this route. the preferred route of therapy in bacterial meningitides is intravenous, supplemented by intramuscular injection. dosage dosage 2 dosage 3

penicillin may have occurred via trace amounts present in milk or vaccines. two types of allergic reactions to penicillin are noted clinically – immediate and delayed. immediate reactions usually occur within 20 minutes of administration and range in severity from urticaria and pruritus to angloneurotic edema, laryngospasm, bronchospasm, hypotension, vascular collapse and death (see warnings ). such immediate anaphylactic reactions are very rare and usually occur after parenteral therapy, but a few cases of anaphylaxis have been reported following oral therapy. another type of immediate reaction, an accelerated reaction, may occur between 20 minutes and 48 hours after administration and may include urticaria, pruritus, fever and, occasionally, laryngeal edema. delayed reactions to penicillin therapy usually occur within 1 to 2 weeks after initiation of therapy. manifestations include serum sickness-like symptoms, i.e., fever, malaise, urticaria, myalgia, arthralgia, abdominal pain and various skin rashes, ranging from maculopapular eruptions to exfoliative dermatitis. contact dermatitis has been observed in individuals who prepare penicillin solutions. gastrointestinal system pseudomembranous colitis has been reported with the onset occurring during or after penicillin g treatment. nausea, vomiting, stomatitis, black or hairy tongue, and other symptoms of gastrointestinal irritation may occur, especially during oral therapy. hematologic system reactions include neutropenia, which resolves after penicillin therapy is discontinued; coombspositive hemolytic anemia, an uncommon reaction, occurs in patients treated with intravenous penicillin g in doses greater than 10 million units/day and who have previously received large doses of the drug; and with large doses of penicillin, a bleeding diathesis, can occur secondary to platelet dysfunction. metabolic buffered penicillin g potassium for injection, usp (1 million units contains 0.3 meq of sodium and 1.68 meq of potassium) may cause serious and even fatal electrolyte disturbances, i.e., hyperkalemia, when given intravenously in large doses. nervous system neurotoxic reactions including hyperreflexia, myoclonic twitches, seizures and coma have been reported following the administration of massive intravenous doses, and are more likely in patients with impaired renal function. urogenital system renal tubular damage and interstitial nephritis have been associated with large intravenous doses of penicillin g. manifestations of this reaction may include fever, rash, eosinophilia, proteinuria, eosinophiluria, hematuria and a rise in serum urea nitrogen. discontinuation of penicillin g results in resolution in the majority of patients. local reactions phlebitis and thrombophlebitis may occur with intravenous administration.

s is predominantly via the kidney. the renal clearance, which is extremely rapid, is the result of glomerular filtration and active tubular transport, with the latter route predominating. urinary recovery is reported to be 58 to 85% of the administered dose. renal clearance of penicillin is delayed in premature infants, neonates and in the elderly due to decreased renal function. the serum half-life of penicillin g correlates inversely with age and clearance of creatinine and ranges from 3.2 hours in infants 0 to 6 days of age to 1.4 hours in infants 14 days of age or older. nonrenal clearance includes hepatic metabolism and, to a lesser extent, biliary excretion. the latter routes become more important with renal impairment. probenecid blocks the renal tubular secretion of penicillin. therefore, the concurrent administration of probenecid prolongs the elimination of penicillin g and, consequently, increases the serum concentrations. penicillin g is distributed to most areas of the body including lung, liver, kidney, muscle, bone and placenta. in the presence of inflammation, levels of penicillin in abscesses, middle ear, pleural, peritoneal and synovial fluids are sufficient to inhibit most susceptible bacteria. penetration into the eye, brain, cerebrospinal fluid (csf) or prostate is poor in the absence of inflammation. with inflamed meninges, the penetration of penicillin g into the csf improves, such that the csf/serum ratio is 2 to 6%. inflammation also enhances its penetration into the pericardial fluid. penicillin g is actively secreted into the bile resulting in levels at least 10 times those achieved simultaneously in serum. penicillin g penetrates poorly into human polymorphonuclear leukocytes. in the presence of impaired renal function, the β-phase serum half-life of penicillin g is prolonged. β-phase serum half-lives of one to two hours were observed in azotemic patients with serum creatinine concentrations <3 mg/100 ml and ranged as high as 20 hours in anuric patients. a linear relationship, including the lowest range of renal function, is found between the serum elimination rate constant and renal function as measured by creatinine clearance. in patients with altered renal function, the presence of hepatic insufficiency further alters the elimination of penicillin g. in one study, the serum half-lives in two anuric patients (excreting <400 ml urine/day) were 7.2 and 10.1 hours. a totally anuric patient with terminal hepatic cirrhosis had a penicillin half-life of 30.5 hours, while another patient with anuria and liver disease had a serum half-life of 16.4 hours. the dosage of penicillin g should be reduced in patients with severe renal impairment, with additional modifications when hepatic disease accompanies the renal impairment. hemodialysis has been shown to reduce penicillin g serum levels. microbiology penicillin g is bactericidal against penicillin-susceptible microorganisms during the stage of active multiplication. it acts by inhibiting biosynthesis of cell-wall mucopeptide. it is not active against the penicillinase-producing bacteria, which include many strains of staphylococci. penicillin g is highly active in vitro against staphylococci (except penicillinase-producing strains), streptococci (groups a, b, c, g, h, l and m), pneumococci and nelsseria meningitidis. other organisms susceptible in vitro to penicillin g are nelsseria gonorrhoeae, corynebacterium diphtheriae, bacillus anthracis, clostridia, actinomyces species, spirillum minus, streptobacillus monillformis, listeria monocytogenes, and leptospira; treponema pallidum is extremely susceptible. some species of gram-negative bacilli were previously considered susceptible to very high intravenous doses of penicillin g (up to 80 million units/day) including some strains of escherichia coli, proteus mirabilis, salmonella, shigella, enterobacter aerogenes (formerly aerobacter aerogenes) and alcaligenes faecalis. penicillin g is no longer considered a drug of choice for infections caused by these organisms. susceptibility testing diffusion techniques the use of antibiotic disk susceptibility test methods which measure zone diameter give an accurate estimation of antibiotic susceptibility. one such standard procedure1 which has been recommended for use with disks to test susceptibility of organisms to penicillin g uses the 10 unit (u) penicillin disk. interpretation involves the correlation of the diameters obtained in the disk test with the minimum inhibitory concentration (mic) for penicillin g. reports from the laboratory giving results of the standard single-disk susceptibility test with a 10 u penicillin disk should be interpreted according to the following criteria: a report of “susceptible” indicates that the pathogen is likely to be inhibited by generally achievable blood levels. a report of “moderately susceptible” suggests that the organism would be susceptible if high dosage is used or if the infection is confined to tissue and fluids (e.g., urine) in which high antibiotic levels are obtained. a report of “resistant” indicates that achievable concentrations are unlikely to be inhibitory and other therapy should be selected. standardized procedures require the use of laboratory control organisms. the 10 u penicillin g disk should give the following zone diameters: dilution techniques when using a standardized dilution method2 (broth, agar, microdilution) or equivalent an organism may be considered susceptible if the minimum inhibitory concentration (mic) values are interpreted according to the following table: mic test results should be interpreted according to the concentration of penicillin g that can be attained in blood (serum), tissue, and body fluids. as with standard diffusion techniques, dilution methods require the use of laboratory control organisms. standard penicillin g powder should provide the following mic values: for anaerobic bacteria the mic of penicillin g can be determined by agar or broth dilution (including microdilution) techniques3. clinical 1 clinical 2 clinical 3 clinical 4

potency.