Second Generation Cephalosporins

Microbiology:
In vitro tests demonstrate that the bactericidal action of the cephalosporins results from inhibition of cell-wall synthesis. Cefaclor 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.

> Aerobes, Gram-positive
Staphylococci, including coagulase-positive, coagulase-negative, and penicillinase-producing strains
Streptococcus pneumoniae
Streptococcus pyogenes (group A β-hemolytic streptococci)

>Aerobes, Gram-negative
Escherichia coli
Haemophilus influenzae, excluding beta-lactamase-negative ampicillin-resistant strains
Klebsiella spp.
Proteus mirabilis

The following in vitro data are available, but their clinical significance is unknown.

Cefaclor exhibits in vitro minimal inhibitory concentrations (MICs) of </=8 µg/mL against most (>/= 90%) strains of the following microorganisms; however, the safety and effectiveness of cefaclor in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled clinical trials.

>Aerobes, Gram-negative
Citrobacter diversus
Moraxella (Branhamella) catarrhalis
Neisseria gonorrhoeae

>Anaerobes, Gram-positive
Bacteroides spp. (excluding Bacteroides fragilis)
Peptococcus
Peptostreptococcus
Propionibacterium acnes

Note: Pseudomonas spp., Acinetobacter calcoaceticus and most strains of enterococci (Enterococcus faecalis, group D streptococci), Enterobacter spp., indole-positive Proteus, Morganella morganii (formerly Proteus morganii), Providencia rettgeri (formerly Proteus rettgeri), and Serratia spp. are resistant to cefaclor. When tested by in vitro methods, staphylococci exhibit cross-resistance between cefaclor and methicillin-type antibiotics.

INDICATIONS AND USAGE:
Cefaclor is indicated in the treatment of the following infections when caused by susceptible strains of the designated microorganisms:

Otitis media caused by Streptococcus pneumoniae, Haemophilus influenzae, staphylococci, and Streptococcus pyogenes

Note: β-lactamase-negative, ampicillin-resistant (BLNAR) strains of Haemophilus influenzae should be considered resistant to cefaclor despite apparent in vitro susceptibility of some BLNAR strains.

Lower respiratory tract infections, including pneumonia, caused by Streptococcus pneumoniae, Haemophilus influenzae, and Streptococcus pyogenes

Note: β-lactamase-negative, ampicillin-resistant (BLNAR) strains of Haemophilus influenzae should be considered resistant to cefaclor despite apparent in vitro susceptibility of some BLNAR strains.

Pharyngitis and Tonsillitis, caused by Streptococcus pyogenes

Note: Penicillin is the usual drug of choice in the treatment and prevention of streptococcal infections, including the prophylaxis of rheumatic fever. Cefaclor is generally effective in the eradication of streptococci from the nasopharynx; however, substantial data establishing the efficacy of cefaclor in the subsequent prevention of rheumatic fever are not available at present.

Urinary tract infections, including pyelonephritis and cystitis, caused by Escherichia coli, Proteus mirabilis, Klebsiella spp., and coagulase-negative staphylococci

Skin and skin structure infections caused by Staphylococcus aureus and Streptococcus pyogenes

Appropriate culture and susceptibility studies should be performed to determine susceptibility of the causative organism to cefaclor.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Cefaclor Capsule and other antibacterial drugs, Cefaclor Capsule 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 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.
DOSAGE AND ADMINISTRATION:
Cefaclor is administered orally.

Adults -- The usual adult dosage is 250 mg every 8 hours. For more severe infections (such as pneumonia) or those caused by less susceptible organisms, doses may be doubled.

Pediatric Patients -- The usual recommended daily dosage for pediatric patients is 20 mg/kg/day in divided doses every 8 hours. In more serious infections, otitis media, and infections caused by less susceptible organisms, 40 mg/kg/day are recommended, with a maximum dosage of 1 g/day.

	Cefaclor Suspension
	20 mg/kg/day
Weight	125 mg/5 mL	250 mg/5 mL
9 kg	1/2 tsp t.i.d.
18 kg	1 tsp t.i.d.	1/2 tsp t.i.d.
	40 mg/kg/day
9 kg	1 tsp t.i.d.	1/2 tsp t.i.d.
18 kg		1 tsp t.i.d.

 

B.I.D. Treatment Option - For the treatment of otitis media and pharyngitis, the total daily dosage may be divided and administered every 12 hours.

	Cefaclor Suspension
	20 mg/kg/day (Pharyngitis)
Weight	187 mg/5 mL	375 mg/5 mL
9 kg	1/2 tsp b.i.d.
18 kg	1 tsp b.i.d.	1/2 tsp b.i.d.
	40 mg/kg/day (Otitis Media)
9 kg	1 tsp b.i.d.	1/2 tsp b.i.d.
18 kg		1 tsp b.i.d.

Cefaclor may be administered in the presence of impaired renal function. Under such a condition, the dosage usually is unchanged.

In the treatment of β-hemolytic streptococcal infections, a therapeutic dosage of cefaclor should be administered for at least 10 days.

SOURCE:
Package insert data:

Microbiology:
The bactericidal action of cefotetan results from inhibition of cell wall synthesis. Cefotetan has in vitro activity against a wide range of aerobic and anaerobic gram-positive and gram-negative organisms. The methoxy group in the 7-alpha position provides cefotetan with a high degree of stability in the presence of beta-lactamases including both penicillinases and cephalosporinases of gram-negative bacteria.

Cefotetan has been shown to be active against most strains of the following organisms both in vitro and in clinical infections (see INDICATIONS AND USAGE).

>Gram-Negative Aerobes
Escherichia coli
Haemophilus influenzae (including ampicillin-resistant strains)
Klebsiella species (including K. pneumoniae)
Morganella morganii
Neisseria gonorrhoeae (nonpenicillinase-producing strains)
Proteus mirabilis
Proteus vulgaris
Providencia rettgeri
Serratia marcescens

NOTE: Approximately one-half of the usually clinically significant strains of Enterobacter species (eg, E. aerogenes and E. cloacae) are resistant to cefotetan. Most strains of Pseudomonas aeruginosa and Acinetobacter species are resistant to cefotetan.

>Gram-Positive Aerobes
Staphylococcus aureus (including penicillinase- and nonpenicillinase-producing strains)
Staphylococcus epidermidis
Streptococcus agalactiae (group B beta-hemolytic streptococcus)
Streptococcus pneumoniae
Streptococcus pyogenes

NOTE: Methicillin-resistant staphylococci are resistant to cephalosporins. Some strains of Staphylococcus epidermidis and most strains of enterococci, eg, Enterococcus faecalis (formerly Streptococcus faecalis) are resistant to cefotetan

>Anaerobes
Prevotella bivia (formerly Bacteroides bivius)
Prevotella disiens (formerly Bacteroides disiens)
Bacteroides fragilis
Prevotella melaninogenica (formerly Bacteroides melaninogenicus)
Bacteroides vulgatus
Fusobacterium species
Gram-positive bacilli (including Clostridium species)  NOTE: Most strains of C. difficile are resistant).
Peptococcus niger
Peptostreptococcus species

NOTE: Many strains of B. distasonis, B. ovatus and B. thetaiotaomicron are resistant to cefotetan in vitro. However, the therapeutic utility of cefotetan against these organisms cannot be accurately predicted on the basis of in vitro susceptibility tests alone.

The following in vitro data are available but their clinical significance is unknown. Cefotetan has been shown to be active in vitro against most strains of the following organisms:

>Gram-Negative Aerobes
Citrobacter species (including C. diversus and C. freundii)
Klebsiella oxytoca
Moraxella (Branhamella) catarrhalis
Neisseria gonorrhoeae (penicillinase-producing strains)
Salmonella species
Serratia species
Shigella species
Yersinia enterocolitica

>Anaerobes
Porphyromonas asaccharolytica (formerly Bacteroides asaccharolyticus)
Prevotella oralis (formerly Bacteroides oralis)
Bacteroides splanchnicus
Clostridium difficile
Propionibacterium species
Veillonella species

INDICATIONS AND USAGE:
To reduce the development of drug-resistant bacteria and maintain the effectiveness of CEFOTAN and other antibacterial drugs, CEFOTAN 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 information are available, they should be considered in selecting or modifying antimicrobial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Treatment
CEFOTAN is indicated for the therapeutic treatment of the following infections when caused by susceptible strains of the designated organisms:

Urinary Tract Infections caused by E. coli, Klebsiella spp (including K. pneumoniae), Proteus mirabilis and Proteus spp (which may include the organisms now called Proteus vulgaris, Providencia rettgeri, and Morganella morganii).

Lower Respiratory Tract Infections caused by Streptococcus pneumoniae, Staphylococcus aureus (penicillinase- and nonpenicillinase-producing strains), Haemophilus influenzae (including ampicillin-resistant strains), Klebsiella species (including K. pneumoniae), E. coli, Proteus mirabilis, and Serratia marcescens*.

Skin and Skin Structure Infections due to Staphylococcus aureus (penicillinase- and nonpenicillinase-producing strains), Staphylococcus epidermidis, Streptococcus pyogenes, Streptococcus species (excluding enterococci), Escherichia coli, Klebsiella pneumoniae, Peptococcus niger*, Peptostreptococcus species.

Gynecologic Infections caused by Staphylococcus aureus, (including penicillinase- and nonpenicillinase-producing strains), Staphylococcus epidermidis, Streptococcus species (excluding enterococci), Streptococcus agalactiae, E. coli, Proteus mirabilis, Neisseria gonorrhoeae, Bacteroides species (excluding B. distasonis, B. ovatus, B. thetaiotaomicron), Fusobacterium species*, and gram-positive anaerobic cocci (including Peptococcus niger and Peptostreptococcus species).

Cefotetan, like other cephalosporins, has no activity against

Chlamydia trachomatis. Therefore, when cephalosporins are used in the treatment of pelvic inflammatory disease, and C. trachomatis is one of the suspected pathogens, appropriate antichlamydial coverage should be added.

Intra-abdominal Infections caused by E. coli, Klebsiella species (including K. pneumoniae), Streptococcus species (excluding enterococci), Bacteroides species (excluding B. distasonis, B. ovatus, B. thetaiotaomicron) and Clostridium species*.

Bone and Joint Infections caused by Staphylococcus aureus.*

*Efficacy for this organism in this organ system was studied in fewer than ten infections.

Specimens for bacteriological examination should be obtained in order to isolate and identify causative organisms and to determine their susceptibilities to cefotetan. Therapy may be instituted before results of susceptibility studies are known; however, once these results become available, the antibiotic treatment should be adjusted accordingly.

In cases of confirmed or suspected gram-positive or gram-negative sepsis or in patients with other serious infections in which the causative organism has not been identified, it is possible to use CEFOTAN concomitantly with an aminoglycoside. Cefotetan combinations with aminoglycosides have been shown to be synergistic in vitro against many Enterobacteriaceae and also some other gram-negative bacteria. The dosage recommended in the labeling of both antibiotics may be given and depends on the severity of the infection and the patient's condition.

NOTE: Increases in serum creatinine have occurred when CEFOTAN was given alone. If CEFOTAN and an aminoglycoside are used concomitantly, renal function should be carefully monitored, because nephrotoxicity may be potentiated.

Prophylaxis
The preoperative administration of CEFOTAN may reduce the incidence of certain postoperative infections in patients undergoing surgical procedures that are classified as clean contaminated or potentially contaminated (eg, cesarean section, abdominal or vaginal hysterectomy, transurethral surgery, biliary tract surgery, and gastrointestinal surgery).

If there are signs and symptoms of infection, specimens for culture should be obtained for identification of the causative organism so that appropriate therapeutic measures may be initiated.

DOSAGE AND ADMINISTRATION:
The usual adult dosage is 1 or 2 grams of Cefotetan for Injection, USP administered intravenously or intramuscularly. Proper dosage and route of administration should be determined by the condition of the patient, severity of the infection, and susceptibility of the causative organism.

General Guidelines for Dosage of Cefotetan for Injection, USP
Type of Infection	Daily Dose	Frequency and Route
Urinary Tract	1 to 4 grams	500 mg every 12 hours IV or IM1 or 2 g every 24 hours IV or IM 1 or 2 g every 12 hours IV or IM
Skin & Skin Structure Mild - Moderatea Severe
	2 grams	2 g every 24 hours IV1 g every 12 hours IV or IM
	4 grams	2 g every 12 hours IV
Other Sites	2 to 4 grams	1 or 2 g every 12 hours IV or IM
Severe	4 grams	2 g every 12 hours IV
Life-Threatening	6 gramsb	3 g every 12 hours IV

a. Klebsiella pneumoniae skin and skin structure infections should be treated with 1 or 2 grams every 12 hours IV or IM.

b. Maximum daily dosage should not exceed 6 grams.

If Chlamydia trachomatis is a suspected pathogen in gynecologic infections, appropriate antichlamydial coverage should be added, since cefotetan has no activity against this organism.

Prophylaxis
To prevent postoperative infection in clean contaminated or potentially contaminated surgery in adults, the recommended dosage is 1 or 2 g of Cefotetan for Injection, USP administered once, intravenously, 30 to 60 minutes prior to surgery. In patients undergoing cesarean section, the dose should be administered as soon as the umbilical cord is clamped.

For Intramuscular Use
Reconstitute with Sterile Water for Injection; Bacteriostatic Water for Injection; Sodium Chloride Injection 0.9%, USP; 0.5% Lidocaine HCl; or 1% Lidocaine HCl. Shake to dissolve and let stand until clear.

Vial Size	Amount of Diluent Added (mL)	Approximate Withdrawable Vol (mL)	Approximate Average Concentration (mg/mL)
1 gram	2	2.5	400
2 gram	3	4	500

Renal Dosing:

DOSAGE GUIDELINES FOR PATIENTS WITH IMPAIRED RENAL FUNCTION
Creatinine Clearance mL/min	Dose	Frequency
> 30	Usual Recommended Dosage*	Every 12 hours
10 to 30	Usual Recommended Dosage*	Every 24 hours
< 10	Usual Recommended Dosage*	Every 48 hours

* Dose determined by the type and severity of infection, and susceptibility of the causative organism.

Alternatively, the dosing interval may remain constant at 12 hour intervals, but the dose reduced to one-half the usual recommended dose for patients with a creatinine clearance of 10 to 30 mL/min, and one-quarter the usual recommended dose for patients with a creatinine clearance of less than 10 mL/min.

When only serum creatinine levels are available, creatinine clearance may be calculated from the following formula. The serum creatinine level should represent a steady state of renal function.

Males: Weight (kg) x (140 - age) / [72 x serum creatinine (mg/100 mL)]
Females: 0.85 x value for males

Cefotetan is dialyzable and it is recommended that for patients undergoing intermittent hemodialysis, one-quarter of the usual recommended dose be given every 24 hours on days between dialysis and one-half the usual recommended dose on the day of dialysis.

SOURCE:
Package insert data:

Microbiology:
The bactericidal action of cefoxitin results from inhibition of cell wall synthesis. Cefoxitin has in vitro activity against a wide range of gram-positive and gram-negative organisms. The methoxy group in the 7a position provides cefoxitin with a high degree of stability in the presence of beta-lactamases, both penicillinases and cephalosporinases, of gram-negative bacteria.

Cefoxitin 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-positive microorganisms
Staphylococcus aureus (including penicillinase-producing strains)
Staphylococcus epidermidis
Streptococcus agalactiae
Streptococcus pneumoniae
Streptococcus pyogenes

Staphylococci resistant to methicillin/oxacillin should be considered resistant to cefoxitin.
Most strains of enterococci, e.g., Enterococcus faecalis, are resistant.

Aerobic gram-negative microorganisms
Escherichia coli
Haemophilus influenzae
Klebsiella spp. (including K. pneumoniae)
Morganella morganii
Neisseria gonorrhoeae (including penicillinase-producing strains)
Proteus mirabilis
Proteus vulgaris
Providencia spp. (including Providencia rettgeri)

Anaerobic gram-positive microorganisms
Clostridium spp.
Peptococcus niger
Peptostreptococcus spp.

Anaerobic gram-negative microorganisms
Bacteroides distasonis
Bacteroides fragilis
Bacteroides ovatus
Bacteroides thetaiotaomicron
Bacteroides spp.

The following in vitro data are available, but their clinical significance is unknown.

Cefoxitin exhibits in vitro minimum inhibitory concentrations (MIC's) of 8 mcg/mL or less for aerobic microorganisms and 16 mcg/mL or less for anaerobic microorganisms against most (>/= 90%) strains of the following microorganisms; however, the safety and effectiveness of cefoxitin in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled clinical trials.

Aerobic gram-negative microorganisms
Eikenella corrodens (non-β-lactamase producers)
Klebsiella oxytoca

Anaerobic gram-positive microorganisms
Clostridium perfringens
Anaerobic gram-negative microorganisms
Prevotella bivia (formerly Bacteroides bivius)

Cefoxitin is inactive in vitro against most strains of Pseudomonas aeruginosa and enterococci and many strains of Enterobacter cloacae.

INDICATIONS AND USAGE:
Treatment
Cefoxitin for Injection, USP is indicated for the treatment of serious infections caused by susceptible strains of the designated microorganisms in the diseases listed below.

(1) Lower respiratory tract infections, including pneumonia and lung abscess, caused by Streptococcus pneumoniae, other streptococci (excluding enterococci, e.g., Enterococcus faecalis [formerly Streptococcus faecalis]), Staphylococcus aureus (including penicillinase-producing strains), Escherichia coli, Klebsiella species, Haemophilus influenzae, and Bacteroides species.
(2) Urinary tract infections caused by Escherichia coli, Klebsiella species, Proteus mirabilis, Morganella morganii, Proteus vulgaris and Providencia species (including P. rettgeri).
(3) Intra-abdominal infections, including peritonitis and intra-abdominal abscess, caused by Escherichia coli, Klebsiella species, Bacteroides species including Bacteroides fragilis, and Clostridium species.
(4) Gynecological infections, including endometritis, pelvic cellulitis, and pelvic inflammatory disease caused by Escherichia coli, Neisseria gonorrhoeae (including penicillinase-producing strains), Bacteroides species including B. fragilis, Clostridium species, Peptococcus niger, Peptostreptococcus species, and Streptococcus agalactiae. Cefoxitin for Injection, USP, like cephalosporins, has no activity against Chlamydia trachomatis. Therefore, when Cefoxitin for Injection, USP is used in the treatment of patients with pelvic inflammatory disease and C. trachomatis is one of the suspected pathogens, appropriate anti-chlamydial coverage should be added.
(5) Septicemia caused by Streptococcus pneumoniae, Staphylococcus aureus (including penicillinase-producing strains), Escherichia coli, Klebsiella species, and Bacteroides species including B. fragilis.
(6) Bone and joint infections caused by Staphylococcus aureus (including penicillinase-producing strains).
(7) Skin and skin structure infections caused by Staphylococcus aureus (including penicillinase-producing strains), Staphylococcus epidermidis, Streptococcus pyogenes and other streptococci (excluding enterococci e.g., Enterococcus faecalis [formerly Streptococcus faecalis]), Escherichia coli, Proteus mirabilis, Klebsiella species, Bacteroides species including B. fragilis, Clostridium species, Peptococcus niger, and Peptostreptococcus species.

Appropriate culture and susceptibility studies should be performed to determine the susceptibility of the causative organisms to Cefoxitin for Injection, USP. Therapy may be started while awaiting the results of these studies.

In randomized comparative studies, Cefoxitin for Injection, USP and cephalothin were comparably safe and effective in the management of infections caused by gram-positive cocci and gram-negative rods susceptible to the cephalosporins. Cefoxitin for Injection, USP has a high degree of stability in the presence of bacterial beta-lactamases, both penicillinases and cephalosporinases.

Many infections caused by aerobic and anaerobic gram-negative bacteria resistant to some cephalosporins respond to Cefoxitin for Injection, USP. Similarly, many infections caused by aerobic and anaerobic bacteria resistant to some penicillin antibiotics (ampicillin, carbenicillin, penicillin G) respond to treatment with Cefoxitin for Injection, USP. Many infections caused by mixtures of susceptible aerobic and anaerobic bacteria respond to treatment with Cefoxitin for Injection, USP.

Prevention
Cefoxitin for Injection, USP is indicated for the prophylaxis of infection in patients undergoing uncontaminated gastrointestinal surgery, vaginal hysterectomy, abdominal hysterectomy, or cesarean section.

If there are signs of infection, specimens for culture should be obtained for identification of the causative organism so that appropriate treatment may be instituted.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Cefoxitin for Injection, USP and other antibacterial drugs, Cefoxitin for Injection, USP 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 information is 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.

DOSAGE AND ADMINISTRATION:
TREATMENT
Adults
The usual adult dosage range is 1 gram to 2 grams every six to eight hours. Dosage should be determined by susceptibility of the causative organisms, severity of infection, and the condition of the patient (see Table 1 for dosage guidelines).

If C. trachomatis is a suspected pathogen, appropriate anti-chlamydial coverage should be added, because cefoxitin sodium has no activity against this organism.

MEFOXIN may be used in patients with reduced renal function with the following dosage adjustments:

In adults with renal insufficiency, an initial loading dose of 1 gram to 2 grams may be given. After a loading dose, the recommendations for maintenance dosage (Table 2) may be used as a guide.

When only the serum creatinine level is available, the following formula (based on sex, weight, and age of the patient) may be used to convert this value into creatinine clearance. The serum creatinine should represent a steady state of renal function.

Males = Weight (kg) x (140-age) / [72 x serum creatinine (mg/100 mL)]
Females = 0.85 x male value

In patients undergoing hemodialysis, the loading dose of 1 to 2 grams should be given after each hemodialysis, and the maintenance dose should be given as indicated in Table 2.

Antibiotic therapy for group A beta-hemolytic streptococcal infections should be maintained for at least 10 days to guard against the risk of rheumatic fever or glomerulonephritis. In staphylococcal and other infections involving a collection of pus, surgical drainage should be carried out where indicated.

Pediatric Patients
The recommended dosage in pediatric patients three months of age and older is 80 to 160 mg/kg of body weight per day divided into four to six equal doses. The higher dosages should be used for more severe or serious infections. The total daily dosage should not exceed 12 grams.

At this time no recommendation is made for pediatric patients from birth to three months of age.

In pediatric patients with renal insufficiency, the dosage and frequency of dosage should be modified consistent with the recommendations for adults (see Table 2).

PREVENTION
Effective prophylactic use depends on the time of administration. MEFOXIN usually should be given one-half to one hour before the operation, which is sufficient time to achieve effective levels in the wound during the procedure. Prophylactic administration should usually be stopped within 24 hours since continuing administration of any antibiotic increases the possibility of adverse reactions but, in the majority of surgical procedures, does not reduce the incidence of subsequent infection.

For prophylactic use in uncontaminated gastrointestinal surgery, vaginal hysterectomy, or abdominal hysterectomy, the following doses are recommended:

Adults:
2 grams administered intravenously just prior to surgery (approximately one-half to one hour before the initial incision) followed by 2 grams every 6 hours after the first dose for no more than 24 hours.

Pediatric Patients (3 months and older):

30 to 40 mg/kg doses may be given at the times designated above.

Cesarean section patients:
For patients undergoing cesarean section, either a single 2 gram dose administered intravenously as soon as the umbilical cord is clamped OR a 3-dose regimen consisting of 2 grams given intravenously as soon as the umbilical cord is clamped followed by 2 grams 4 and 8 hours after the initial dose is recommended.

Table 1: Guidelines for Dosage of MEFOXIN

Type of Infection	Daily Dosage	Frequency and Route
*Including patients in whom bacteremia is absent or unlikely.
Uncomplicated forms* of infections such as pneumonia, urinary tract infection, cutaneous infection	3-4 grams	1 gram every 6-8 hours IV
Moderately severe or severe infections	6-8 grams	1 gram every 4 hours or 2 grams every 6-8 hours IV
Infections commonly needing antibiotics in higher dosage (e.g., gas gangrene)	12 grams	2 grams every 4 hours or 3 grams every 6 hours IV

Renal Dosing: -----------------------------

Table 2: Maintenance Dosage of MEFOXIN in Adults with Reduced Renal Function

Renal Function	Creatinine Clearance (mL/min)	Dose (grams)	Frequency
Mild impairment	50-30	1-2	every 8-12 hours
Moderate impairment	29-10	1-2	every 12-24 hours
Severe impairment	9-5	0.5-1	every 12-24 hours
Essentially no function	<5	0.5-1	every 24-48 hours

 

Table 3: Preparation of Solution for Intravenous Administration

Strength	Amount of Diluent to be Added (mL)*	Approximate Withdrawable Volume (mL)	Approximate Average Concentration (mg/mL)
*Shake to dissolve and let stand until clear.
1 gram Vial	10	10.5	95
2 gram Vial	10 or 20	11.1 or 21.0	180 or 95
1 gram Infusion Bottle	50 or 100	50 or 100	20 or 10
2 gram Infusion Bottle	50 or 100	50 or 100	40 or 20
10 gram Bulk	43 or 93	49 or 98.5	200 or 100

SOURCE:
Package insert data:

INDICATIONS AND USAGE:
To reduce the development of drug-resistant bacteria and maintain the effectiveness of cefprozil and other antibacterial drugs, cefprozil 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 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. Cefprozil Tablets USP are indicated for the treatment of patients with mild to moderate infections caused by susceptible strains of the designated microorganisms in the conditions listed below:

UPPER RESPIRATORY TRACT
Pharyngitis/tonsillitis caused by Streptococcus pyogenes.

NOTE: The usual drug of choice in the treatment and prevention of streptococcal infections, including the prophylaxis of rheumatic fever, is penicillin given by the intramuscular route. Cefprozil is generally effective in the eradication of Streptococcus pyogenes from the nasopharynx; however, substantial data establishing the efficacy of cefprozil in the subsequent prevention of rheumatic fever are not available at present.

Otitis Media caused by Streptococcus pneumoniae, Haemophilus influenzae (including beta-lactamase-producing strains), and Moraxella (Branhamella) catarrhalis (including beta-lactamase-producing strains). (See CLINICAL STUDIES.)

NOTE: In the treatment of otitis media due to beta-lactamase producing organisms, cefprozil had bacteriologic eradication rates somewhat lower than those observed with a product containing a specific beta-lactamase inhibitor. In considering the use of cefprozil, lower overall eradication rates should be balanced against the susceptibility patterns of the common microbes in a given geographic area and the increased potential for toxicity with products containing beta-lactamase inhibitors.

Acute Sinusitis caused by Streptococcus pneumoniae, Haemophilus influenzae (including beta-lactamase-producing strains), and Moraxella (Branhamella) catarrhalis (including beta-lactamase-producing strains).

LOWER RESPIRATORY TRACT
Secondary Bacterial Infection of Acute Bronchitis and Acute Bacterial Exacerbation of Chronic Bronchitis caused by Streptococcus pneumoniae, Haemophilus influenzae (including beta-lactamase-producing strains), and Moraxella (Branhamella) catarrhalis (including beta-lactamase-producing strains).

SKIN AND SKIN STRUCTURE
Uncomplicated Skin and Skin-Structure Infections caused by Staphylococcus aureus (including penicillinase-producing strains) and Streptococcus pyogenes. Abscesses usually require surgical drainage.

DOSAGE AND ADMINISTRATION:
Cefprozil Tablets USP are administered orally.

Population/Infection	Dosage (mg)	Duration (days)
ADULTS (13 years and older)
UPPER RESPIRATORY TRACT
Pharyngitis/Tonsillitis	500 q 24h	10 a
Acute Sinusitis	250 q 12h or	10
(For moderate to severe infections, the higher dose should be used)	500 q 12h
LOWER RESPIRATORY TRACT
Secondary Bacterial Infection of Acute Bronchitis and Acute Bacterial Exacerbation of Chronic Bronchitis	500 q 12h	10
SKIN AND SKIN STRUCTURE
Uncomplicated Skin and Skin Structure Infections	250 q 12h or 500 q 24h or   500 q 12h	10
CHILDREN (2 years to 12 years)
UPPER RESPIRATORY TRACT b
Pharyngitis/Tonsillitis	7.5 mg/kg q 12h	10 a
SKIN AND SKIN STRUCTURE b
Uncomplicated Skin and Skin Structure Infections	20 mg/kg q 24h	10
INFANTS & CHILDREN (6 months to 12 years)
UPPER RESPIRATORY TRACT b
Otitis Media	15 mg/kg q 12h	10
(See INDICATIONS AND USAGE)
Acute Sinusitis	7.5 mg/kg q 12h	10
(For moderate to severe infections, the higher dose should be used)	or 15 mg/kg q 12h

a. In the treatment of infections due to Streptococcus pyogenes, cefprozil should be administered for at least 10 days.
b. Not to exceed recommended adult doses

Renal Dosing:
Cefprozil may be administered to patients with impaired renal function. The following dosage schedule should be used.

Creatinine Clearance (mL/min)	Dosage(mg)	Dosing Interval
30 to 120	standard	standard
0 to 29*	50% of standard	standard

*Cefprozil is in part removed by hemodialysis; therefore, cefprozil should be administered after the completion of hemodialysis.

SOURCE:
Package insert data:

Microbiology:
Cefuroxime has in vitro activity against a wide range of gram-positive and gram-negative organisms, and it is highly stable in the presence of beta-lactamases of certain gram-negative bacteria. The bactericidal action of cefuroxime results from inhibition of cell-wall synthesis.

Cefuroxime is usually active against the following organisms in vitro:

Aerobes, Gram-positive: Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, and Streptococcus pyogenes (and other streptococci).

NOTE: Most strains of enterococci, e.g., Enterococcus faecalis (formerly Streptococcus faecalis), are resistant to cefuroxime. Methicillin-resistant staphylococci and Listeria monocytogenes are resistant to cefuroxime.

Aerobes, Gram-negative: Citrobacter spp., Enterobacter spp., Escherichia coli, Haemophilus influenzae (including ampicillin-resistant strains), Haemophilus parainfluenzae, Klebsiella spp., (including Klebsiella pneumoniae), Moraxella (Branhamella) catarrhalis (including ampicillin- and cephalothin-resistant strains), Morganella morganii (formerly Proteus morganii), Neisseria gonorrhoeae (including penicillinase- and non–penicillinase-producing strains), Neisseria meningitidis, Proteus mirabilis, Providencia rettgeri (formerly Proteus rettgeri), Salmonella spp., and Shigella spp.

NOTE: Some strains of Morganella morganii, Enterobacter cloacae, and Citrobacter spp. have been shown by in vitro tests to be resistant to cefuroxime and other cephalosporins. Pseudomonas and Campylobacter spp., Legionella spp., Acinetobacter calcoaceticus, and most strains of Serratia spp. and Proteus vulgaris are resistant to most first- and second-generation cephalosporins.

Anaerobes: Gram-positive and gram-negative cocci (including Peptococcus and Peptostreptococcus spp.), gram-positive bacilli (including Clostridium spp.), and gram-negative bacilli (including Bacteroides and Fusobacterium spp.).

NOTE: Clostridium difficile and most strains of Bacteroides fragilis are resistant to cefuroxime.

INDICATIONS AND USAGE:
To reduce the development of drug-resistant bacteria and maintain the effectiveness of cefuroxime and other antibacterial drugs, cefuroxime 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 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.

Cefuroxime for injection is indicated for the treatment of patients with infections caused by susceptible strains of the designated organisms in the following diseases:

• Lower Respiratory Tract Infections, including pneumonia, caused by Streptococcus pneumoniae, Haemophilus influenzae (including ampicillin-resistant strains), Klebsiella spp., Staphylococcus aureus (penicillinase- and non–penicillinase-producing strains), Streptococcus pyogenes, and Escherichia coli.
• Urinary Tract Infections caused by Escherichia coli and Klebsiella spp.
• Skin and Skin-Structure Infections caused by Staphylococcus aureus (penicillinase- and non-penicillinase-producing strains), Streptococcus pyogenes, Escherichia coli, Klebsiella spp., and Enterobacter spp.
• Septicemia caused by Staphylococcus aureus (penicillinase- and non-penicillinase-producing strains), Streptococcus pneumoniae, Escherichia coli, Haemophilus influenzae (including ampicillin-resistant strains), and Klebsiella spp.
• Meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae (including ampicillin-resistant strains), Neisseria meningitidis, and Staphylococcus aureus (penicillinase- and non–penicillinase-producing strains).
• Gonorrhea: Uncomplicated and disseminated gonococcal infections due to Neisseria gonorrhoeae (penicillinase- and non–penicillinase-producing strains) in both males and females.
• Bone and Joint Infections caused by Staphylococcus aureus (penicillinase- and non–penicillinase-producing strains).

Clinical microbiological studies in skin and skin-structure infections frequently reveal the growth of susceptible strains of both aerobic and anaerobic organisms. Cefuroxime has been used successfully in these mixed infections in which several organisms have been isolated.

In certain cases of confirmed or suspected gram-positive or gram-negative sepsis or in patients with other serious infections in which the causative organism has not been identified, cefuroxime may be used concomitantly with an aminoglycoside (see PRECAUTIONS). The recommended doses of both antibiotics may be given depending on the severity of the infection and the patient's condition.

Prevention: The preoperative prophylactic administration of cefuroxime may prevent the growth of susceptible disease-causing bacteria and thereby may reduce the incidence of certain postoperative infections in patients undergoing surgical procedures (e.g., vaginal hysterectomy) that are classified as clean-contaminated or potentially contaminated procedures. Effective prophylactic use of antibiotics in surgery depends on the time of administration. Cefuroxime should usually be given one-half to 1 hour before the operation to allow sufficient time to achieve effective antibiotic concentrations in the wound tissues during the procedure. The dose should be repeated intraoperatively if the surgical procedure is lengthy.

Prophylactic administration is usually not required after the surgical procedure ends and should be stopped within 24 hours. In the majority of surgical procedures, continuing prophylactic administration of any antibiotic does not reduce the incidence of subsequent infections but will increase the possibility of adverse reactions and the development of bacterial resistance.

The perioperative use of cefuroxime has also been effective during open heart surgery for surgical patients in whom infections at the operative site would present a serious risk. For these patients it is recommended that therapy with cefuroxime be continued for at least 48 hours after the surgical procedure ends. If an infection is present, specimens for culture should be obtained for the identification of the causative organism, and appropriate antimicrobial therapy should be instituted.

DOSAGE AND ADMINISTRATION:
Dosage: Adults: The usual adult dosage range for cefuroxime is 750 mg to 1.5 grams every 8 hours, usually for 5 to 10 days. In uncomplicated urinary tract infections, skin and skin-structure infections, disseminated gonococcal infections, and uncomplicated pneumonia, a 750 mg dose every 8 hours is recommended. In severe or complicated infections, a 1.5 gram dose every 8 hours is recommended.

In bone and joint infections, a 1.5 gram dose every 8 hours is recommended. In clinical trials, surgical intervention was performed when indicated as an adjunct to therapy with cefuroxime. A course of oral antibiotics was administered when appropriate following the completion of parenteral administration of cefuroxime.

In life-threatening infections or infections due to less susceptible organisms, 1.5 grams every 6 hours may be required. In bacterial meningitis, the dosage should not exceed 3 grams every 8 hours. The recommended dosage for uncomplicated gonococcal infection is 1.5 grams given intramuscularly as a single dose at 2 different sites together with 1 gram of oral probenecid. For preventive use for clean-contaminated or potentially contaminated surgical procedures, a 1.5 gram dose administered intravenously just before surgery (approximately one-half to 1 hour before the initial incision) is recommended. Thereafter, give 750 mg intravenously or intramuscularly every 8 hours when the procedure is prolonged.

For preventive use during open heart surgery, a 1.5 gram dose administered intravenously at the induction of anesthesia and every 12 hours thereafter for a total of 6 grams is recommended.

Renal Dosing:
A reduced dosage must be employed when renal function is impaired. Dosage should be determined by the degree of renal impairment and the susceptibility of the causative organism

Creatinine Clearance (mL/min)	Dose	Frequency
* Since cefuroxime is dialyzable, patients on hemodialysis should be given a further dose at the end of the dialysis.
> 20	750 mg to 1.5 grams	q8h
10 - 20	750 mg	q12h
< 10	750 mg	q24h*

When only serum creatinine is available, the following formula (based on sex, weight, and age of the patient) may be used to convert this value into creatinine clearance. The serum creatinine should represent a steady state of renal function.

Males: Weight (kg) x (140 - age) / [72 x serum creatinine (mg/100 mL)]
Females: 0.85 x value for males

NOTE: As with antibiotic therapy in general, administration of cefuroxime should be continued for a minimum of 48 to 72 hours after the patient becomes asymptomatic or after evidence of bacterial eradication has been obtained; a minimum of 10 days of treatment is recommended in infections caused by Streptococcus pyogenes in order to guard against the risk of rheumatic fever or glomerulonephritis; frequent bacteriologic and clinical appraisal is necessary during therapy of chronic urinary tract infection and may be required for several months after therapy has been completed; persistent infections may require treatment for several weeks; and doses smaller than those indicated above should not be used. In staphylococcal and other infections involving a collection of pus, surgical drainage should be carried out where indicated.

Pediatric Patients Above 3 Months of Age: Administration of 50 to 100 mg/kg per day in equally divided doses every 6 to 8 hours has been successful for most infections susceptible to cefuroxime. The higher dosage of 100 mg/kg per day (not to exceed the maximum adult dosage) should be used for the more severe or serious infections.

In bone and joint infections, 150 mg/kg per day (not to exceed the maximum adult dosage) is recommended in equally divided doses every 8 hours. In clinical trials, a course of oral antibiotics was administered to pediatric patients following the completion of parenteral administration of cefuroxime.

In cases of bacterial meningitis, a larger dosage of cefuroxime is recommended, 200 to 240 mg/kg per day intravenously in divided doses every 6 to 8 hours.

In pediatric patients with renal insufficiency, the frequency of dosing should be modified consistent with the recommendations for adults.

SOURCE:
Package insert data:

INDICATIONS AND USAGE:
NOTE: CEFTIN TABLETS AND CEFTIN FOR ORAL SUSPENSION ARE NOT BIOEQUIVALENT AND ARE NOT SUBSTITUTABLE ON A MILLIGRAM-PER-MILLIGRAM BASIS.

CEFTIN Tablets

CEFTIN Tablets are indicated for the treatment of patients with mild to moderate infections caused by susceptible strains of the designated microorganisms in the conditions listed below:

1.Pharyngitis/Tonsillitis caused by Streptococcus pyogenes.

NOTE: The usual drug of choice in the treatment and prevention of streptococcal infections, including the prophylaxis of rheumatic fever, is penicillin given by the intramuscular route. CEFTIN Tablets are generally effective in the eradication of streptococci from the nasopharynx; however, substantial data establishing the efficacy of cefuroxime in the subsequent prevention of rheumatic fever are not available. Please also note that in all clinical trials, all isolates had to be sensitive to both penicillin and cefuroxime. There are no data from adequate and well-controlled trials to demonstrate the effectiveness of cefuroxime in the treatment of penicillin-resistant strains of Streptococcus pyogenes.

2. Acute Bacterial Otitis Media caused by Streptococcus pneumoniae, Haemophilusinfluenzae(including beta-lactamase-producing strains), Moraxellacatarrhalis (including beta-lactamase-producing strains), or Streptococcus pyogenes.

3. Acute Bacterial Maxillary Sinusitis caused by Streptococcus pneumoniaeorHaemophilusinfluenzae (non-beta-lactamase-producing strains only) (see CLINICAL STUDIES).

NOTE: In view of the insufficient numbers of isolates of beta-lactamase-producing strains of Haemophilusinfluenzae and Moraxellacatarrhalis that were obtained from clinical trials with CEFTIN Tablets for patients with acute bacterial maxillary sinusitis, it was not possible to adequately evaluate the effectiveness of CEFTIN Tablets for sinus infections known, suspected, or considered potentially to be caused by beta-lactamase-producing Haemophilusinfluenzae or Moraxellacatarrhalis.

4. Acute Bacterial Exacerbations of Chronic Bronchitis and Secondary Bacterial Infections of Acute Bronchitis caused by Streptococcus pneumoniae, Haemophilusinfluenzae(beta-lactamase negative strains), or Haemophilusparainfluenzae (beta-lactamase negative strains) (see DOSAGE AND ADMINISTRATION and CLINICAL STUDIES).

5. Uncomplicated Skin and Skin-Structure Infections caused by Staphylococcus aureus (including beta-lactamase-producing strains) or Streptococcus pyogenes.

6. Uncomplicated Urinary Tract Infections caused by Escherichia coli or Klebsiellapneumoniae.

7. Uncomplicated Gonorrhea, urethral and endocervical, caused by penicillinase-producing and non-penicillinase-producing strains of Neisseriagonorrhoeae and uncomplicated gonorrhea, rectal, in females, caused by non-penicillinase-producing strains of Neisseriagonorrhoeae.

8. Early Lyme Disease (erythemamigrans) caused by Borreliaburgdorferi.

CEFTIN for Oral Suspension

CEFTIN for Oral Suspension is indicated for the treatment of pediatric patients 3 months to 12 years of age with mild to moderate infections caused by susceptible strains of the designated microorganisms in the conditions listed below. The safety and effectiveness of CEFTIN for Oral Suspension in the treatment of infections other than those specifically listed below have not been established either by adequate and well-controlled trials or by pharmacokinetic data with which to determine an effective and safe dosing regimen.

1. Pharyngitis/Tonsillitis caused by Streptococcus pyogenes.

NOTE: The usual drug of choice in the treatment and prevention of streptococcal infections, including the prophylaxis of rheumatic fever, is penicillin given by the intramuscular route. CEFTIN for Oral Suspension is generally effective in the eradication of streptococci from the nasopharynx; however, substantial data establishing the efficacy of cefuroxime in the subsequent prevention of rheumatic fever are not available. Please also note that in all clinical trials, all isolates had to be sensitive to both penicillin and cefuroxime. There are no data from adequate and well-controlled trials to demonstrate the effectiveness of cefuroxime in the treatment of penicillin-resistant strains of Streptococcus pyogenes.

2. Acute Bacterial Otitis Media caused by Streptococcus pneumoniae, Haemophilusinfluenzae(including beta-lactamase-producing strains), Moraxellacatarrhalis (including beta-lactamase-producing strains), or Streptococcus pyogenes.

3. Impetigo caused by Staphylococcus aureus (including beta-lactamase-producing strains) or Streptococcus pyogenes.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of CEFTIN and other antibacterial drugs, CEFTIN 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 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.

DOSAGE AND ADMINISTRATION:
CEFTIN Tablets (May be administered without regard to meals.)

Population/Infection	Dosage	Duration (days)
Adolescents and Adults (13 years and older)
Pharyngitis/tonsillitis	250 mg b.i.d.	10
Acute bacterial maxillary sinusitis	250 mg b.i.d.	10
Acute bacterial exacerbations of chronic bronchitis	250 or 500 mg b.i.d.	10a
Secondary bacterial infections of acute bronchitis	250 or 500 mg b.i.d.	5-10
Uncomplicated skin and skin-structure infections	250 or 500 mg b.i.d.	10
Uncomplicated urinary tract infections	250 mg b.i.d.	7-10
Uncomplicated gonorrhea	1,000 mg once	single dose
Early Lyme disease	500 mg b.i.d.	20
Pediatric Patients (who can swallow tablets whole)
Acute otitis media	250 mg b.i.d.	10
Acute bacterial maxillary sinusitis	250 mg b.i.d.	10

a. The safety and effectiveness of CEFTIN administered for less than 10 days in patients with acute exacerbations of chronic bronchitis have not been established.

CEFTIN for Oral Suspension
CEFTIN for Oral Suspension may be administered to pediatric patients ranging in age from 3 months to 12 years
(Must be administered with food. Shake well each time before using.)

Population/Infection	Dosage	Daily Maximum Dose	Duration (days)
Pediatric Patients (3 months to 12 years)
Pharyngitis/tonsillitis	20 mg/kg/day divided b.i.d.	500 mg	10
Acute otitis media	30 mg/kg/day divided b.i.d.	1,000 mg	10
Acute bacterial maxillary sinusitis	30 mg/kg/day divided b.i.d.	1,000 mg	10
Impetigo	30 mg/kg/day divided b.i.d.	1,000 mg	10

Renal Dosing:
The safety and efficacy of cefuroxime axetil in patients with renal failure have not been established. Since cefuroxime is renally eliminated, its half-life will be prolonged in patients with renal failure.

HOW SUPPLIED:

CEFTIN Tablets
CEFTIN Tablets, 250 mg of cefuroxime (as cefuroxime axetil), are white, capsule-shaped, film-coated tablets engraved with "GX ES7" on one side and blank on the other side as follows:

20 Tablets/Bottle NDC 0173-0387-00
CEFTIN Tablets, 500 mg of cefuroxime (as cefuroxime axetil), are white, capsule-shaped, film-coated tablets engraved with "GX EG2" on one side and blank on the other side as follows:

20 Tablets/Bottle NDC 0173-0394-00
Store the tablets between 15° and 30°C (59° and 86°F). Replace cap securely after each opening.

CEFTIN for Oral Suspension
CEFTIN for Oral Suspension is provided as dry, white to off-white, tutti-frutti-flavored powder. When reconstituted as directed, CEFTIN for Oral Suspension provides the equivalent of 125 mg or 250 mg of cefuroxime (as cefuroxime axetil) per 5 mL of suspension. It is supplied in amber glass bottles as follows:

125 mg/5 mL:
100-mL Suspension NDC 0173-0740-00

250 mg/5 mL:
50-mL Suspension NDC 0173-0741-10
100-mL Suspension NDC 0173-0741-00

Before reconstitution, store dry powder between 2° and 30°C (36° and 86°F).

After reconstitution, immediately store suspension between 2° and 8°C (36° and 46°F), in a refrigerator. DISCARD AFTER 10 DAYS.

SOURCE:
Package insert data:

INDICATIONS AND USAGE:
Lorabid is indicated in the treatment of patients with mild to moderate infections caused by susceptible strains of the designated microorganisms in the conditions listed below. (As recommended dosages, durations of therapy, and applicable patient populations vary among these infections, please see DOSAGE AND ADMINISTRATION for specific recommendations.)

Lower Respiratory Tract
Secondary Bacterial Infection of Acute Bronchitis caused by S. pneumoniae, H. influenzae (includingbeta-lactamase-producing strains), or M. catarrhalis (including beta-lactamase-producing strains).

Acute Bacterial Exacerbations of Chronic Bronchitis caused by S. pneumoniae, H. influenzae (includingbeta-lactamase-producing strains), or M. catarrhalis (including beta-lactamase-producing strains).

Pneumonia caused by S. pneumoniae or H. influenzae (non-beta-lactamase-producing strains only). Data are insufficient at this time to establish efficacy in patients with pneumonia caused by beta-lactamase-producing strains of H. influenzae.

Upper Respiratory Tract
Otitis Media † caused by S. pneumonia, H. influenzae (including beta-lactamase-producing strains), M. catarrhalis (including beta-lactamase-producing strains), or S. pyogenes.

Acute Maxillary Sinusitis† caused by S. pneumoniae, H. influenzae (non-beta-lactamase-producing strains only), or M. catarrhalis (includingbeta-lactamase-producing strains). Data are insufficient at this time to establish efficacy in patients with acute maxillary sinusitis caused by beta-lactamase-producing strains of H. influenzae.

† NOTE: In a patient population with significant numbers of beta-lactamase-producing organisms, loracarbef's clinical cure and bacteriological eradication rates were somewhat less than those observed with a product containing a beta-lactamase inhibtor. Lorabid's decreased potential for toxicity compared to products containing beta-lactamase inhibitors along with the susceptibility patterns of the common microbes in a given geographic area should be taken into account when considering the use of an antimicrobial.

Pharyngitis and Tonsillitis caused by S. pyogenes. (The usual drug of choice in the treatment and prevention of streptococcal infections, including the prophylaxis of rheumatic fever, is penicillin administered by the intramuscular route. Lorabid is generally effective in the eradication of S. pyogenes from the nasopharynx; however, data establishing the efficacy of Lorabid in the subsequent prevention of rheumatic fever are not available at present.)

Skin and Skin Structure
Uncomplicated Skin and Skin Structure Infections caused by S. aureus (including penicillinase-producing strains) or S. pyogenes. Abscesses should be surgically drained as clinically indicated.

Urinary Tract
Uncomplicated Urinary Tract Infections (cystitis) caused by E.coli or S. saprophyticus*.

NOTE: In considering the use of Lorabid in the treatment of cystitis, Lorabid's lower bacterial eradication rates and lower potential for toxicity should be weighed against the increased eradication rates and increased potential for toxicity demonstrated by some other classes of approved agents (see CLINICAL STUDIES section).

Uncomplicated Pyelonephritis caused by E. coli.

*Although treatment of infections due to this organism in this organ system demonstrated a clinically acceptable overall outcome, efficacy was studied in fewer than 10 infections.

Culture and susceptibility testing should be performed when appropriate to determine the causative organism and its susceptibility to loracarbef. Therapy may be started while awaiting the results of these studies. Once these results become available, antimicrobial therapy should be adjusted accordingly.

DOSAGE AND ADMINISTRATION:
Lorabid is administered orally either at least 1 hour prior to eating or at least 2 hours after eating. The recommended dosages, durations of treatment, and applicable patient populations are described in the following chart:

	DOSAGE	Duration
POPULATION/INFECTION	(mg)	(days)
ADULTS (13 years and older)
Lower Respiratory Tract
Secondary Bacterial Infection of Acute Bronchitis	200–400 q12h	7
Acute Bacterial Exacerbation of Chronic Bronchitis	400 q12h	7
Pneumonia	400 q12h	14
Upper Respiratory Tract
Pharyngitis/Tonsillitis	200 q12h	10a
Sinusitis	400 q12h	10
Skin and Skin Structure
Uncomplicated Skin and Skin Structure Infections	200 q12h	7
Urinary Tract
Uncomplicated cystitis	200 q24h	7
Uncomplicated pyelonephritis	400 q12h	14
PEDIATRIC PATIENTS (6 months to 12 years)
Upper Respiratory Tract
Acute Otitis Mediab	30 mg/kg/day in	10
	divided doses q12h
Acute maxillary sinusitis	30 mg/kg/day in	10
	divided doses q12h
Pharyngitis/Tonsillitis	15 mg/kg/day in	10a
	divided doses q12h
Skin and Skin Structure
Impetigo	15 mg/kg/day in	7
	divided doses q12h

a. In the treatment of infections due to S. pyogenes, Lorabid should be administered for at least 10 days.

b. Otitis media should be treated with the suspension. Clinical studies of otitis media were conducted with the suspension formulation only. The suspension is more rapidly absorbed than the capsules, resulting in higher peak plasma concentrations when administered at the same dose. Therefore, the capsule should not be substituted for the suspension in the treatment of otitis media.

Renal Dosing:
Lorabid may be administered to patients with impaired renal function. The usual dose and schedule may be employed in patients with creatinine clearance levels of 50 mL/min or greater. Patients with creatinine clearance between 10 and 49 mL/min may be given half of the recommended dose at the usual dosage interval, or the normal recommended dose at twice the usual dosage interval. Patients with creatinine clearance levels less than 10 mL/min may be treated with the recommended dose given every 3 to 5 days; patients on hemodialysis should receive another dose following dialysis.

When only the serum creatinine is available, the following formula (based on sex, weight, and age of the patient) may be used to convert this value into creatinine clearance (CLcr, mL/min). The equation assumes the patient's renal function is stable.

Males =  [(weight in kg) x (140 - age)]  / [(72) x serum creatinine (mg/100 mL)]
Females = (0.85) x (above value)

SOURCE:
Package insert data: