AZACTAM- aztreonam injection, powder, for solution
E.R. Squibb Sons, L.L.C.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of AZACTAM? and other antibacterial drugs, AZACTAM should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.
DESCRIPTION
AZACTAM? (aztreonam for injection, USP) contains the active ingredient aztreonam, monobactam. It was originally isolated from Chromobacterium violaceum. It is synthetic bactericidal antibiotic.
The monobactams, having unique monocyclic beta-lactam nucleus, are structurally different from other beta-lactam antibiotics (eg, penicillins, cephalosporins, cephamycins). The sulfonic acid substituent in the 1-position of the ring activates the beta-lactam moiety; an aminothiazolyl oxime side chain in the 3-position and methyl group in the 4-position confer the specific antibacterial spectrum and beta-lactamase stability.
Aztreonam is designated chemically as (Z)-2-[[[(2-amino-4-thiazolyl)[[(2S,3S)-2-methyl-4-oxo-1-sulfo-3-azetidinyl]carbamoyl]methylene]amino]oxy]-2-methylpropionic acid
C13 H17 N5 O8 S2 MW 435.44
AZACTAM is sterile, nonpyrogenic, sodium-free, white powder containing approximately 780 mg arginine per gram of aztreonam. Following constitution, the product is for intramuscular or intravenous use. Aqueous solutions of the product have pH in the range of 4.5 to 7.5.
Microbiology
Mechanism of Action
Aztreonam is bactericidal agent that acts by inhibition of bacterial cell wall synthesis. Aztreonam has activity in the presence of some beta-lactamases, both penicillinases and cephalosporinases, of Gram-negative and Gram-positive bacteria.
Mechanism of Resistance
Resistance to aztreonam is primarily through hydrolysis by beta-lactamase, alteration of penicillin-binding proteins (PBPs), and decreased permeability.
Interaction with Other Antimicrobials
Aztreonam and aminoglycosides have been shown to be synergistic in vitro against most strains of P. aeruginosa many strains of Enterobacteriaceae, and other Gram-negative aerobic bacilli.
Aztreonam has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section.
Aerobic Gram-negative microorganisms:
Citrobacter
species
Enterobacter
species
Escherichia coli
Haemophilus influenzae
(including ampicillin-resistant and other penicillinase-producing strains)
Klebsiella oxytoca
Klebsiella pneumoniae
Proteus mirabilis
Pseudomonas aeruginosa
Serratia
species
The following in vitro data are available, but their clinical significance is unknown. At least 90% of the following microorganisms exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for aztreonam. However, the efficacy of aztreonam in treating clinical infections due to these microorganisms has not been established in adequate and well-controlled clinical trials.
Aerobic Gram-negative microorganisms:
Aeromonas hydrophila
Morganella morganii
Neisseria gonorrhoeae
(including penicillinase-producing strains)
Pasteurella multocida
Proteus vulgaris
Providencia stuartii
Providencia rettgeri
Yersinia enterocolitica
Aztreonam and aminoglycosides have been shown to be synergistic in vitro against most strains of P. aeruginosa many strains of Enterobacteriaceae, and other Gram-negative aerobic bacilli.
Alterations of the anaerobic intestinal flora by broad-spectrum antibiotics may decrease colonization resistance, thus permitting overgrowth of potential pathogens, eg, Candida and Clostridium species. Aztreonam has little effect on the anaerobic intestinal microflora in in vitro studies. Clostridium difficile and its cytotoxin were not found in animal models following administration of aztreonam
INDICATIONS AND USAGE
To reduce the development of drug-resistant bacteria and maintain the effectiveness of AZACTAM (aztreonam for injection, USP) and other antibacterial drugs, AZACTAM should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility info. 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.
AZACTAM is indicated for the treatment of the following infections caused by susceptible Gram-negative microorganisms:
Urinary Tract Infections (complicated and uncomplicated), including pyelonephritis and cystitis (initial and recurrent) caused by Escherichia coli Klebsiella pneumoniae Proteus mirabilis Pseudomonas aeruginosa Enterobacter cloacae Klebsiella oxytoca *, Citrobacter species*, and Serratia marcescens *.
Lower Respiratory Tract Infections including pneumonia and bronchitis caused by Escherichia coli Klebsiella pneumoniae Pseudomonas aeruginosa Haemophilus influenzae Proteus mirabilis Enterobacter species, and Serratia marcescens *.
Septicemia caused by Escherichia coli Klebsiella pneumoniae Pseudomonas aeruginosa Proteus mirabilis *, Serratia marcescens *, and Enterobacter species.
Skin and Skin-Structure Infections including those associated with postoperative wounds, ulcers, and burns, caused by Escherichia coli Proteus mirabilis Serratia marcescens Enterobacter species, Pseudomonas aeruginosa Klebsiella pneumoniae and Citrobacter species*.
Intra-abdominal Infections including peritonitis caused by Escherichia coli Klebsiella species including K. pneumoniae Enterobacter species including E. cloacae *, Pseudomonas aeruginosa Citrobacter species* including C. freundii *, and Serratia species* including S. marcescens *.
Gynecologic Infections including endometritis and pelvic cellulitis caused by Escherichia coli Klebsiella pneumoniae *, Enterobacter species* including E. cloacae *, and Proteus mirabilis *.
AZACTAM is indicated for adjunctive therapy to surgery in the management of infections caused by susceptible organisms, including abscesses, infections complicating hollow viscus perforations, cutaneous infections, and infections of serous surfaces. AZACTAM is effective against most of the commonly encountered Gram-negative aerobic pathogens seen in general surgery.
Concurrent Therapy
Concurrent initial therapy with other antimicrobial agents and AZACTAM is recommended before the causative organism(s) is known in seriously ill patients who are also at risk of having an infection due to Gram-positive aerobic pathogens. If anaerobic organisms are also suspected as etiologic agents, therapy should be initiated using an anti-anaerobic agent concurrently with AZACTAM (see DOSAGE AND ADMINISTRATION). Certain antibiotics (eg, cefoxitin, imipenem) may induce high levels of beta-lactamase in vitro in some Gram-negative aerobes such as Enterobacter and Pseudomonas species, resulting in antagonism to many beta-lactam antibiotics including aztreonam. These in vitro findings suggest that such beta-lactamase-inducing antibiotics not be used concurrently with aztreonam. Following identification and susceptibility testing of the causative organism(s), appropriate antibiotic therapy should be continued.
DOSAGE AND ADMINISTRATION
Dosage in Adult Patients
AZACTAM may be administered intravenously or by intramuscular injection. Dosage and route of administration should be determined by susceptibility of the causative organisms, severity and site of infection, and the condition of the patient.
Type of Infection
Dose
Frequency(hours)
* Maximum recommended dose is g per day.
Urinary tract infections
500 mg or g
8 or 12
Moderately severe systemic infections
1 or g
8 or 12
Severe systemic or life-threatening infections
2 g
6 or 8
Because of the serious nature of infections due to Pseudomonas aeruginosa dosage of g every six or eight hours is recommended, at least upon initiation of therapy, in systemic infections caused by this organism.
The intravenous route is recommended for patients requiring single doses greater than g or those with bacterial septicemia, localized parenchymal abscess (eg, intra-abdominal abscess), peritonitis, or other severe systemic or life-threatening infections.
The duration of therapy depends on the severity of infection. Generally, AZACTAM should be continued for at least 48 hours after the patient becomes asymptomatic or evidence of bacterial eradication has been obtained. Persistent infections may require treatment for several weeks. Doses smaller than those indicated should not be used.
Renal Impairment in Adult Patients
Prolonged serum levels of aztreonam may occur in patients with transient or persistent renal insufficiency. Therefore, the dosage of AZACTAM should be halved in patients with estimated creatinine clearances between 10 and 30 mL/min/1.73 m2 after an initial loading dose of or g.
When only the serum creatinine concentration is available, the following formula (based on sex, weight, and age of the patient) may be used to approximate the creatinine clearance (Clcr). The serum creatinine should represent steady state of renal function.
weight (kg) (140?age)
Males: Clcr ??????????????? 72 serum creatinine (mg/dL)
Females: 0.85 above value
In patients with severe renal failure (creatinine clearance less than 10 mL/min/1.73 m2), such as those supported by hemodialysis, the usual dose of 500 mg, g, or g should be given initially. The maintenance dose should be one-fourth of the usual initial dose given at the usual fixed interval of 6, 8, or 12 hours. For serious or life-threatening infections, in addition to the maintenance doses, one-eighth of the initial dose should be given after each hemodialysis session.
