Cefoxitin

Cefoxitin is a prescription medication used to treat bacterial infections, including lung, urinary tract, abdomen, blood, skin, bone, joint, and gynecological infections. Cefoxitin belongs to a group of drugs called cephalosporin antibiotics, which work to stop the growth of bacteria in the body.

This medication is available in an injectable form to be given directly into a vein (IV) by a healthcare professional.

Common side effects of cefoxitin include irritation at the site of injection, rash, fever, and diarrhea.

Serious side effects have been reported with cefoxitin including:

• hypersensitivity (severe allergic reaction). Signs of a hypersensitivity reaction, which include the following:
  • chest pain
  • swelling of the face, eyes, lips, tongue, arms, or legs
  • difficulty breathing or swallowing
  • fainting
  • rash
• diarrhea. Diarrhea is a common problem caused by antibiotics, and it usually ends when the antibacterial is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as 2 or more months after having taken their last dose of the antibacterial. If diarrhea is severe or lasts more than 2 or 3 days, contact your doctor, as this may be a sign of an infection of the bowels.
• superinfection: Cefoxitin should not be used for extended periods. Prolonged use can lead to the growth of dangerous organisms that are resistant or unresponsive to this medication. Take cefoxitin for the duration prescribed by your doctor.

Do not take cefoxitin if you:

• are allergic to cefoxitin or to any of its ingredients
• are allergic to similar antibiotics (penicillins, cephalosporins)

Take cefoxitin exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The cefoxitin dose your doctor recommends will be based on:

• the condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication
• your kidney function
• your weight
• your age

The recommended dose range for cefoxitin in adults is 0.5 to 12 grams once a day or divided into daily doses (reason for use and kidney function).

The recommended dose range for cefoxitin in children is 30 mg/kg per day to 12 grams per day, typically divided into daily doses (depending on reason for use and kidney function).

Cefoxitin is in a group of drugs called cephalosporin (SEF a low spor in) antibiotics. It works by fighting bacteria in your body.

Cefoxitin is used to treat many kinds of bacterial infections, including severe or life-threatening forms.

Cefoxitin may also be used for purposes other than those listed in this medication guide.

You should not use this medication if you are allergic to cefoxitin or to similar antibiotics, such as cefdinir (Omnicef), cefprozil (Cefzil), cefuroxime (Ceftin), cephalexin (Keflex), and others.

Use the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.

Cefoxitin can harm your kidneys. This effect is increased when you also use certain other medicines, including: antivirals, chemotherapy, injected antibiotics, medicine for bowel disorders, medicine to prevent organ transplant rejection, injectable osteoporosis medication, and some pain or arthritis medicines (including aspirin, Tylenol, Advil, and Aleve).

Other drugs may interact with cefoxitin, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

Use cefoxitin as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as an infusion into a vein over a period of time.
• It may be given as a shot into a vein.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

Clinical Pharmacology

Following an intravenous dose of 1 gram, serum concentrations were 110 mcg/mL at 5 minutes, declining to less than 1 mcg/mL at 4 hours. The half-life after an intravenous dose is 41 to 59 minutes. Approximately 85 percent of Cefoxitin is excreted unchanged by the kidneys over a 6-hour period, resulting in high urinary concentrations. Probenecid slows tubular excretion and produces higher serum levels and increases the duration of measurable serum concentrations.

Cefoxitin passes into pleural and joint fluids and is detectable in antibacterial concentrations in bile.

In a published study of geriatric patients ranging in age from 64 to 88 years with normal renal function for their age (creatinine clearance ranging from 31.5 to 174.0 mL/min), the half-life for Cefoxitin ranged from 51 to 90 minutes, resulting in higher plasma concentrations than in younger adults. These changes were attributed to decreased renal function associated with the aging process.

Microbiology

Mechanism of Action

Cefoxitin is a bactericidal agent that acts by inhibition of bacterial cell wall synthesis. Cefoxitin 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 Cefoxitin is primarily through hydrolysis by beta-lactamase, alteration of penicillin-binding proteins (PBPs), and decrease permeability.

Cefoxitin 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:

Gram-positive bacteria

Staphylococcus aureus (methicillin-susceptible isolates only)

Staphylococcus epidermidis (methicillin-susceptible isolates only)

Streptococcus agalactiae

Streptococcus pneumoniae

Streptococcus pyogenes

Gram-negative bacteria

Escherichia coli

Haemophilus influenzae

Klebsiella spp.

Morganella morganii

Neisseria gonorrhoeae

Proteus mirabilis

Proteus vulgaris

Providencia spp.

Anaerobic bacteria

Clostridium spp.

Peptococcus niger

Peptostreptococcus spp.

Bacteroides spp.

The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following microorganism exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for Cefoxitin. However, the efficacy of Cefoxitin in treating clinical infections due to these microorganisms has not been established in adequate and well-controlled clinical trials.

Gram-negative bacteria

Eikenella corrodens (non-β-lactamase producers)

Anaerobic bacteria

Clostridium perfringens

Prevotella bivia

Susceptibility Test Methods

When available, the clinical microbiology laboratory should provide the results of in vitro susceptibility test results for antimicrobial drug products used in resident hospitals 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 an antibacterial drug product for treatment.

Dilution Techniques

Quantitative methods are used to determine antimicrobial minimal inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized test method1,3. The MIC values should be interpreted according to the criteria provided in Table 1.

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 method2,3. This procedure uses paper disks impregnated with 30 mcg Cefoxitin to test the susceptibility of microorganisms to Cefoxitin. The disk diffusion interpretive criteria are provided in Table 1.

Table 1. Susceptibility Test Interpretive Criteria for Cefoxitin2,4

a The clinical effectiveness of Cefoxitin for treating organisms that produce intermediate results

is unknown2.

b Values derived using either Brucella blood or Wilkins Chalgren agar are considered equivalent. Values for agar and broth microdilution are considered equivalent4.

A report of Susceptible indicates that the antimicrobial is likely to inhibit growth of the pathogen if the antimicrobial compound reaches the concentration at the infection site necessary to inhibit growth of the pathogen. 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 high dosage of drug can be used. This category also provides a buffer zone which 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 reaches the concentrations usually achievable at the infection site; other therapy should be selected.

Quality Control

Standardized susceptibility test procedures require the use of laboratory controls to monitor and ensure the accuracy and precision of the supplies and reagents used in the assay, and the techniques of the individual performing the test1,2,3,4. Standard Cefoxitin powder should provide the following range of MIC values noted in Table 2. For the diffusion technique using the 30 mcg disk, the criteria in Table 1 should be achieved.

Table 2. Acceptable Quality Control Ranges for Cefoxitin

BEFORE THERAPY WITH Cefoxitin FOR INJECTION IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO Cefoxitin, CEPHALOSPORINS, PENICILLINS, OR OTHER DRUGS. THIS PRODUCT SHOULD BE GIVEN WITH CAUTION TO PENICILLIN-SENSITIVE PATIENTS. ANTIBIOTICS SHOULD BE ADMINISTERED WITH CAUTION TO ANY PATIENT WHO HAS DEMONSTRATED SOME FORM OF ALLERGY, PARTICULARLY TO DRUGS. IF AN ALLERGIC REACTION TO Cefoxitin FOR INJECTION OCCURS, DISCONTINUE THE DRUG. SERIOUS HYPERSENSITIVITY REACTIONS MAY REQUIRE EPINEPHRINE AND OTHER EMERGENCY MEASURES.

Clostridium difficile associated diarrhea (CDAD) has been reported with the use of nearly all antibacterial agents, including Cefoxitin, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD.

Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

Cefoxitin for Injection, USP is a dry white to off-white powder supplied in conventional vials containing Cefoxitin sodium as follows:

The container closure is not made with natural rubber latex.

Special storage instructions

Cefoxitin for Injection, USP in the dry state should be stored between 2º to 25ºC (36º to 77ºF). Avoid exposure to temperatures above 50ºC. The dry material as well as solutions tend to darken, depending on storage conditions; product potency, however, is not adversely affected.

NDC 44567-245-85

Cefoxitin for Injection, USP

1 gram per vial

For Intravenous Use

Rx only

• Mefoxin [DSC]

• Antibiotic, Cephalosporin (Second Generation)

Monitor renal function periodically when used in combination with other nephrotoxic drugs; prothrombin time. Observe for signs and symptoms of anaphylaxis during first dose.

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience diarrhea. Have patient report immediately to prescriber signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), signs of myasthenia gravis (muscle weakness, difficulty chewing, difficulty swallowing, difficulty breathing, droopy eyelids, vision changes, blurred vision, or double vision), bruising, bleeding, severe loss of strength and energy, chills, pharyngitis, seizures, injection site irritation, flushing, shortness of breath, severe dizziness, passing out, dark urine, jaundice, or signs of Clostridium difficile (C. diff)-associated diarrhea (abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools) (rare) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

Lower respiratory tract infections (including pneumonia and lung abscess), urinary tract infections, intraabdominal infections (including peritonitis and intraabdominal abscess), gynecological infections (including endometritis, pelvic cellulitis, and pelvic inflammatory disease), septicemia, bone and joint infections, and skin and skin structure infections:
Uncomplicated infections (bacteremia is absent or unlikely): 1 g IV every 6 to 8 hours
Moderately severe or severe infections: 1 g IV every 4 hours or 2 g IV every 6 to 8 hours
Severe, life-threatening infections: 2 g IV every 4 hours or 3 g IV every 6 hours

Lower respiratory tract infections (including pneumonia and lung abscess), urinary tract infections, intraabdominal infections (including peritonitis and intraabdominal abscess), gynecological infections (including endometritis, pelvic cellulitis, and pelvic inflammatory disease), septicemia, bone and joint infections, and skin and skin structure infections:
Uncomplicated infections (bacteremia is absent or unlikely): 1 g IV every 6 to 8 hours
Moderately severe or severe infections: 1 g IV every 4 hours or 2 g IV every 6 to 8 hours
Severe, life-threatening infections: 2 g IV every 4 hours or 3 g IV every 6 hours

1 to 2 g IV as soon as the umbilical cord is clamped and may be followed by 1 to 2 g IV 4 and 8 hours after the initial dose

(Not approved by FDA)

CDC recommendations:
Uncomplicated infections of the cervix, urethra, or rectum: 2 g IM as a single dose with probenecid 1 g orally as a single dose

This regimen with probenecid is recommended if ceftriaxone is not an option.

Doxycycline therapy for 7 days (if not pregnant) or single dose azithromycin is also recommended to treat possible concurrent chlamydial infection.

The patient's sexual partner(s) should also be evaluated/treated.

Lower respiratory tract infections (including pneumonia and lung abscess), urinary tract infections, intraabdominal infections (including peritonitis and intraabdominal abscess), gynecological infections (including endometritis, pelvic cellulitis, and pelvic inflammatory disease), septicemia, bone and joint infections, and skin and skin structure infections:
3 months or older: 80 to 160 mg/kg/day IV divided in 4 to 6 equal doses
Maximum dose: 12 g/day

3 months or older: 80 to 160 mg/kg/day IV divided in 4 to 6 equal doses
Maximum dose: 12 g/day

CDC recommendations for adolescents:
Mild-to-moderately severe infections:
When parenteral regimen is used: 2 g IV every 6 hours plus oral or IV doxycycline

Parenteral therapy should be continued for at least 24 hours after clinical improvement is demonstrated. Oral therapy with doxycycline should then be continued to complete 14 days of treatment.

When oral regimen is used: 2 g IM as a single dose with probenecid 1 g orally as a single dose plus oral doxycycline (with or without oral metronidazole) for 14 days

The patient's sexual partner(s) should also be evaluated/treated.

Hemodialysis:
Adults:
Loading dose: 1 to 2 g IV after each hemodialysis

Maintenance dose:
CrCl 30 to 50 mL/min: 1 to 2 g IV every 8 to 12 hours
CrCl 10 to 29 mL/min: 1 to 2 g IV every 12 to 24 hours
CrCl 5 to 9 mL/min: 0.5 to 1 g IV every 12 to 24 hours
CrCl less than 5 mL/min: 0.5 to 1 g IV every 24 to 48 hours

Pediatric patients with renal insufficiency: The dosage and dosage frequency should be adjusted consistent with the recommendations for adults.

The duration of cefoxitin therapy depends on the type of infection. Antibiotic therapy for group A beta-hemolytic streptococcal infections should be continued for at least 10 days. In staphylococcal and other infections involving a collection of pus, surgical drainage is recommended where indicated.

If Chlamydia trachomatis is a suspected pathogen, appropriate antichlamydial coverage should be added, because cefoxitin has no activity against this organism.

To reduce the development of drug-resistant organisms, antibiotics should only be used for prophylaxis or treatment of infections that are proven or strongly suspected to be due to bacteria. Culture and susceptibility information should be considered when selecting treatment or, if no data are available, local epidemiology and susceptibility patterns may be considered when selecting empiric therapy. Patients should be advised to avoid missing doses and to complete the entire course of therapy.

Substance Name

Cefoxitin

CAS Registry Number

35607-66-0

Drug Class

Antiinfective Agents

Antibacterial Agents

Cephalosporins