Trovan I.V.

TROVAN is indicated for the treatment of patients initiating therapy in in-patient health care facilities (i.e., hospitals and long term nursing care facilities) with serious, life- or limb-threatening infections caused by susceptible strains of the designated microorganisms in the conditions listed below. (See DOSAGE AND ADMINISTRATION .)

Nosocomial pneumonia caused by Escherichia coli , Pseudomonas aeruginosa , Haemophilus influenzae , or Staphylococcus aureus . As with other antimicrobials, where Pseudomonas aeruginosa is a documented or presumptive pathogen, combination therapy with either an aminoglycoside or aztreonam may be clinically indicated.

Community acquired pneumonia caused by Streptococcus pneumoniae , Haemophilus influenzae , Klebsiella pneumoniae , Staphylococcus aureus , Mycoplasma pneumoniae , Moraxella catarrhalis , Legionella pneumophila , or Chlamydia pneumoniae .

Complicated intra-abdominal infections, including post-surgical infections caused by Escherichia coli , Bacteroides fragilis , viridans group streptococci, Pseudomonas aeruginosa , Klebsiella pneumoniae , Peptostreptococcus species, or Prevotella species .

Gynecologic and pelvic infections including endomyometritis, parametritis, septic abortion and post-partum infections caused by Escherichia coli , Bacteroides fragilis , viridans group streptococci, Enterococcus faecalis , Streptococcus agalactiae , Peptostreptococcus species, Prevotella species, or Gardnerella vaginalis .

Complicated skin and skin structure infections, including diabetic foot infections, caused by Staphylococcus aureus , Streptococcus agalactiae , Pseudomonas aeruginosa , Enterococcus faecalis , Escherichia coli , or Proteus mirabilis . NOTE : TROVAN has not been studied in the treatment of osteomyelitis. (See WARNINGS .)

TROVAN is contraindicated in persons with a history of hypersensitivity to trovafloxacin, alatrofloxacin, quinolone antimicrobial agents or any other components of these products.

General:

Moderate to severe phototoxicity reactions have been observed in patients who are exposed to direct sunlight while receiving some drugs in this class. Therapy should be discontinued if phototoxicity (e.g., a skin eruption, etc.) occurs.

The safety and efficacy of TROVAN in patients with severe cirrhosis (Child-Pugh Class C) have not been studied.

Symptomatic pancreatitis has been reported on therapy. Clinicians should monitor pancreatic tests in patients who develop symptoms consistent with pancreatitis as clinically indicated.

Because a rapid or bolus intravenous injection may result in life-threatening hypotension, alatrofloxacin should only be administered by slow intravenous infusion over a period of 60 minutes. Profound hypotension has also been reported in patients receiving alatrofloxacin at the recommended rate of infusion. (See WARNINGS and DOSAGE AND ADMINISTRATION : Intravenous Administration .)

Information for Patients:

Patients should be advised:

• to discontinue therapy and to inform their physician immediately if they develop symptoms suggestive of hepatic dysfunction including fatigue, anorexia, vomiting, abdominal pain, jaundice, dark urine or pale stool. (See WARNINGS .)
• to inform their physician if they develop symptoms suggestive of pancreatitis including abdominal pain and/or nausea and vomiting. (See PRECAUTIONS : General .)
• that TROVAN Tablets may be taken without regard to meals;
• that vitamins or minerals containing iron, aluminum- or magnesium-base antacids, antacids containing citric acid buffered with sodium citrate, or sucralfate or Videx , (Didanosine), chewable/buffered tablets or the pediatric powder for oral solution, should be taken at least 2 hours before or 2 hours after taking TROVAN tablets. (See PRECAUTIONS : Drug Interactions .);
• that TROVAN may cause lightheadedness and/or dizziness. Dizziness and/or lightheadedness was the most common adverse reaction reported, and for females under 45 years, it was reported significantly more frequently than in other groups. The incidence of dizziness may be substantially reduced if TROVAN Tablets are taken at bedtime or with food. Patients should know how they react to trovafloxacin before they operate an automobile or machinery or engage in activities requiring mental alertness and coordination. (See WARNINGS and ADVERSE REACTIONS .);
• to discontinue treatment and inform their physician if they experience pain, inflammation or rupture of a tendon, and to rest and refrain from exercise until the diagnosis of tendinitis or tendon rupture has been confidently excluded;
• that TROVAN may be associated with hypersensitivity reactions, even following the first dose, and to discontinue the drug at the first sign of a skin rash, hives or other skin reactions, difficulty in swallowing or breathing, any swelling suggesting angioedema (e.g., swelling of the lips, tongue, face, tightness of the throat, hoarseness), or other symptoms of an allergic reaction. (See WARNINGS and ADVERSE REACTIONS .);
• to avoid excessive sunlight or artificial ultraviolet light (e.g., tanning beds) while taking TROVAN and to discontinue therapy if phototoxicity (e.g., sunburn-like reaction or skin eruption) occurs.
• that convulsions have been reported in patients taking quinolones, including trovafloxacin, and to notify their physician before taking this drug if there is a history of this condition.

Drug Interactions:

Antacids, Sucralfate, and Iron: The absorption of oral trovafloxacin is significantly reduced by the concomitant administration of some antacids containing magnesium or aluminum, citric acid/sodium citrate (Bicitra ), as well as sucralfate and iron (ferrous ions). These agents as well as formulations containing divalent and trivalent cations such as Videx , (Didanosine), chewable/buffered tablets or the pediatric powder for oral solution, should be taken at least 2 hours before or 2 hours after oral trovafloxacin administration. (See CLINICAL PHARMACOLOGY .)

Morphine: Co-administration of intravenous morphine significantly reduces the absorption of oral trovafloxacin. Intravenous morphine should be administered at least 2 hours after oral TROVAN dosing in the fasted state and at least 4 hours after oral TROVAN is taken with food. Trovafloxacin administration had no effect on the pharmacokinetics of morphine or its metabolite, morphine-6-(beta)-glucuronide. (See CLINICAL PHARMACOLOGY .)

Warfarin: There have been reports during the post-marketing experience that trovafloxacin/alatrofloxacin enhance the effects of warfarin, including cases of bleeding. The mechanism for this reaction is unknown. Prothrombin time, International Normalized Ratio (INR) or other suitable anticoagulation tests should be closely monitored if trovafloxacin/alatrofloxacin is administered concomitantly with warfarin. Patients should also be monitored for evidence of bleeding.

Minor pharmacokinetic interactions without clinical significance have been observed with co-administration of TROVAN Tablets with caffeine, omeprazole and calcium carbonate. (See CLINICAL PHARMACOLOGY .)

No significant pharmacokinetic interactions with theophylline, cimetidine, digoxin, warfarin, or cyclosporine have been observed with TROVAN Tablets. (See CLINICAL PHARMACOLOGY .)

Alatrofloxacin should not be co-administered with any solution containing multivalent cations, e.g., magnesium, through the same intravenous line. (See DOSAGE AND ADMINISTRATION .)

Laboratory Test Interactions:

There are no reported laboratory test interactions.

Carcinogenesis, Mutagenesis, Impairment of Fertility:

Long term studies in animals to determine the carcinogenic potential of trovafloxacin or alatrofloxacin have not been conducted.

TROVAN did not shorten the time to development of UV-induced skin tumors in hairless albino (Skh-1) mice; thus, it was not photo co-carcinogenic in this model. These mice received oral trovafloxacin and concurrent irradiation with simulated sunlight 5 days per week for 40 weeks followed by a 12-week treatment-free observation period. The daily dose of UV radiation used in this study was approximately 30% of the minimal dose of UV radiation that would induce erythema in Caucasian humans. The median time to the development of skin tumors in the hairless mice (42-43 weeks) was similar in the vehicle control group and those given 10 or 30 mg/kg of trovafloxacin daily. At a dose level of 30 mg/kg/day, the mice had skin trovafloxacin concentrations of approximately 7 µg/g. Following multiple 200 mg daily doses of trovafloxacin, the amount in human skin is estimated to be about 3 µg/g, based upon plasma concentrations measured at this dose level.

Trovafloxacin was not mutagenic in the Ames Salmonella reversion assay or CHO/HGPRT mammalian cell gene mutation assay and it was not clastogenic in mitogen-stimulated human lymphocytes or mouse bone marrow cells. A mouse micronucleus test conducted with alatrofloxacin was also negative. The positive response observed in the E. coli bacterial mutagenicity assay may be due to the inhibition of DNA gyrase by trovafloxacin.

Trovafloxacin and alatrofloxacin did not affect the fertility of male or female rats at oral and I.V. doses of 75 mg/kg/day and 50 mg/kg/day, respectively. These doses are 15 and 10 times the recommended maximum human dose based on mg/kg or approximately 2 times based on mg/m 2 . However, oral doses of trovafloxacin at 200 mg/kg/day (40 times the recommended maximum human dose based on mg/kg or about 6 times based on mg/m 2 ) were associated with increased preimplantation loss in rats.

Pregnancy: Teratogenic Effects. Pregnancy Category C:

An increase in skeletal variations was observed in rat fetuses after daily oral 75 mg/kg maternal doses of trovafloxacin (approximately 15 times the highest recommended human dose based on mg/kg or 2 times based upon body surface area) were administered during organogenesis. However, fetal skeletal variations were not observed in rats dosed orally with 15 mg/kg trovafloxacin. Evidence of fetotoxicity (increased perinatal mortality and decreased body weights) was also observed in rats at 75 mg/kg. Daily oral doses of trovafloxacin at 45 mg/kg (approximately 9 times the highest recommended human dose based on mg/kg or 2.7 times based upon body surface area) in the rabbit were not associated with an increased incidence of fetal skeletal variations or malformations.

An increase in skeletal variations and malformations was observed in rat fetuses after daily intravenous doses of alatrofloxacin at >/=20 mg/kg/day (approximately 4 times the highest recommended human dose based on mg/kg or 0.6 times based upon body surface area) were administered to dams during organogenesis. In the rabbit, an increase in fetal skeletal malformations was also observed when 20 mg/kg/day (approximately equal to the highest recommended human dose based upon body surface area) of alatrofloxacin was given intravenously during the period of organogenesis. Intravenous dosing of alatrofloxacin at 6.5 mg/kg in the rat or rabbit was not associated with an increased incidence of skeletal variations or malformations. Fetotoxicity and fetal skeletal malformations have been associated with other quinolones.

Oral doses of trovafloxacin >5mg/kg were associated with an increased gestation time in rats, and several dams at 75 mg/kg experienced uterine dystocia.

There are no adequate and well-controlled studies in pregnant women. TROVAN should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. (See WARNINGS .)

Nursing Mothers:

Trovafloxacin is excreted in human milk and was found in measurable concentrations in the breast milk of lactating subjects. (See CLINICAL PHARMACOLOGY , Distribution .)

Because of the potential for unknown effects from trovafloxacin in nursing infants from mothers taking trovafloxacin, a decision should be made either to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use:

The safety and effectiveness of trovafloxacin in pediatric patients and adolescents less than 18 years of age have not been established. Quinolones, including trovafloxacin, cause arthropathy and osteochondrosis in juvenile animals of several species. (See WARNINGS .)

Geriatric Use:

In multiple-dose clinical trials of trovafloxacin, 27% of patients were >/=65 years of age and 12% of patients were >/=75 years of age. The overall incidence of drug-related adverse reactions, including central nervous system and gastrointestinal side effects, was less in the >/=65 year group than the other age groups.

The recommended dosage for TROVAN for the treatment of serious, life- or limb-threatening infections is described in the table below. Doses of TROVAN are administered once every 24 hours. TROVAN should not usually be administered for more than 2 weeks. It should only be administered for longer than 2 weeks if the treating physician believes the benefits to the individual patients clearly outweigh the risks of such longer-term treatment. (See boxed WARNING .)

Oral doses should be administered at least 2 hours before or 2 hours after antacids containing magnesium or aluminum, as well as sucralfate, citric acid buffered with sodium citrate (e.g., Bicitra ), metal cations (e.g., ferrous sulfate) and Videx , (Didanosine), chewable/buffered tablets or the pediatric powder for oral solution.

Intravenous morphine should be administered at least 2 hours after oral TROVAN dosing in the fasted state and at least 4 hours after oral TROVAN is taken with food.

Patients whose therapy is started with TROVAN I.V. may be switched to TROVAN Tablets to complete the course of therapy, if deemed appropriate by the treating physician. In certain patients with serious and life- or limb-threatening infections as described in the INDICATIONS AND USAGE Section, TROVAN Tablets may be considered appropriate initial therapy, when the treating physician believes that the benefit of the product for the patient outweighs the potential risk.

TROVAN I.V. (alatrofloxacin mesylate injection) should only be administered by INTRAVENOUS infusion. It is not for intramuscular, intrathecal, intraperitoneal, or subcutaneous administration.

Single-use vials require dilution prior to administration. (See PREPARATION OF ALATROFLOXACIN MESYLATE INJECTION FOR ADMINISTRATION .)

NOTE: As with other antimicrobials, where Pseudomonas aeruginosa is a documented or presumptive pathogen, combination therapy with either an aminoglycoside or aztreonam may be clinically indicated.

IMPAIRED RENAL FUNCTION:   No adjustment in the dosage of TROVAN is necessary in patients with impaired renal function. Trovafloxacin is eliminated primarily by biliary excretion. Trovafloxacin is not efficiently removed from the body by hemodialysis.

CHRONIC HEPATIC DISEASE (cirrhosis):   The following table provides dosing guidelines for patients with mild or moderate cirrhosis (Child-Pugh Class A and B). There are no data in patients with severe cirrhosis (Child-Pugh Class C).

INTRAVENOUS ADMINISTRATION

AFTER DILUTION WITH AN APPROPRIATE DILUENT, TROVAN I.V. SHOULD BE ADMINISTERED BY INTRAVENOUS INFUSION OVER A PERIOD OF 60 MINUTES. CAUTION: RAPID OR BOLUS INTRAVENOUS INFUSION SHOULD BE AVOIDED. (See PRECAUTIONS .)

TROVAN I.V. is supplied in single-use vials containing a concentrated solution of alatrofloxacin mesylate in Water for Injection (equivalent of 200 mg or 300 mg as trovafloxacin). Each mL contains alatrofloxacin mesylate equivalent to 5 mg trovafloxacin. (See HOW SUPPLIED for container sizes.) THESE TROVAN I.V. SINGLE-USE VIALS MUST BE FURTHER DILUTED WITH AN APPROPRIATE SOLUTION PRIOR TO INTRAVENOUS ADMINISTRATION. This parenteral drug product should be inspected visually for discoloration and particulate matter prior to dilution and administration. Since no preservative or bacteriostatic agent is present in this product, aseptic technique must be used in preparation of the final parenteral solution.

PREPARATION OF ALATROFLOXACIN MESYLATE INJECTION FOR ADMINISTRATION

The intravenous dose should be prepared by aseptically withdrawing the appropriate volume of concentrate from the vials of TROVAN I.V. This should be diluted with a suitable intravenous solution to a final concentration of 1-2 mg/mL. (See Compatible Intravenous Solutions .) The resulting solution should be infused over a period of 60 minutes by direct infusion or through a Y-type intravenous infusion set which may already be in place.

Since the vials are for single use only, any unused portion should be discarded.

Since only limited data are available on the compatibility of alatrofloxacin intravenous injection with other intravenous substances, additives or other medications should not be added to TROVAN I.V. in single-use vials or infused simultaneously through the same intravenous line.

If the same intravenous line is used for sequential infusion of several different drugs, the line should be flushed before and after infusion of TROVAN I.V. with an infusion solution compatible with TROVAN I.V. and with any other drug(s) administered via this common line.

If TROVAN I.V. is to be given concomitantly with another drug, each drug should be given separately in accordance with the recommended dosage and route of administration for each drug.

The desired dosage of TROVAN I.V. may be prepared according to the following chart:

For example, to prepare a 200 mg dose at an infusion concentration of 2 mg/mL (as trovafloxacin), 40 mL of TROVAN I.V. is withdrawn from a vial and diluted with 60 mL of a compatible intravenous fluid to produce a total infusion solution volume of 100 mL.

Compatible Intravenous Solutions:

5% Dextrose Injection, USP

0.45% Sodium Chloride Injection, USP

5% Dextrose and 0.45% Sodium Chloride Injection, USP

5% Dextrose and 0.2% Sodium Chloride Injection, USP

Lactated Ringer's and 5% Dextrose Injection, USP

TROVAN I.V. should not be diluted with 0.9% Sodium Chloride Injection, USP (normal saline), alone or in combination with other diluents. A precipitate may form under these conditions. In addition, TROVAN I.V. should not be diluted with Lactated Ringer's, USP.

Normal saline, 0.9% Sodium Chloride Injection, USP can be used for flushing I.V. lines prior to or after administration of TROVAN I.V.

Stability of TROVAN I.V. as Supplied:

When stored under recommended conditions, TROVAN I.V., as supplied in 40 mL or 60 mL vials, is stable through the expiration date printed on the label.

Stability of TROVAN I.V. Following Dilution:

TROVAN I.V., when diluted with compatible intravenous solutions to concentrations of 0.5 to 2.0 mg/mL (as trovafloxacin), is physically and chemically stable for up to 7 days when refrigerated or up to 3 days at room temperature stored in glass bottles or plastic (PVC type) intravenous containers.

Trovan Tablets and Injection are being distributed only to hospitals and long term nursing care facilities for patients initiating therapy in these facilities.

Tablets

TROVAN (trovafloxacin mesylate) Tablets are available as blue, film-coated tablets. The 100 mg tablets are round and contain trovafloxacin mesylate equivalent to 100 mg trovafloxacin. The 200 mg tablets are modified oval-shaped and contain trovafloxacin mesylate equivalent to 200 mg trovafloxacin.

TROVAN Tablets are packaged and in unit dose blister strips in the following configurations:

100-mg tablets: color: blue; shape: round; debossing: "PFIZER" on one side and "378" on the other

Bottles of 30 (NDC 0049-3780-30)

Unit Dose/40 tablets (NDC 0049-3780-43)

200-mg tablets: color: blue; shape: modified oval; debossing: "PFIZER" on one side and "379" on the other

Bottles of 30 (NDC 0049-3790-30)

Unit Dose/40 tablets (NDC 0049-3790-43)

Storage

TROVAN Tablets should be stored at 15°C to 30°C (59°F to 86°F) in airtight containers (USP).

Injection

TROVAN is also available for intravenous administration as the prodrug, TROVAN I.V. (alatrofloxacin mesylate injection), in the following configurations:

Single-use vials containing a clear, colorless to pale-yellow concentrated solution of alatrofloxacin mesylate equivalent to 5 mg trovafloxacin/mL.

5 mg/mL, 40 mL, 200 mg

Unit dose package (NDC 0049-3890-28)

5 mg/mL, 60 mL, 300 mg

Unit dose package (NDC 0049-3900-28)

Storage

TROVAN I.V. should be stored at 15°C to 30°C (59°F to 86°F). Protect From Light. Do Not Freeze.

PRODUCT PHOTO(S):

ANIMAL PHARMACOLOGY

Quinolones have been shown to cause arthropathy in immature animals.

Arthropathy and chondrodysplasia were observed in immature animals given trovafloxacin. (See WARNINGS .)

At doses from 10 to 15 times the human dose based on mg/kg or approximately 3 to 5 times based on mg/m 2 , trovafloxacin has been shown to cause arthropathy in immature rats and dogs. In addition, these drugs are associated with an increased incidence of chondrodysplasia in rats compared to controls. There is no evidence of arthropathies in fully mature rats and dogs at doses from 40 or 10 times the human dose based on mg/kg or approximately 5 times based on mg/m 2 for a 6 month exposure period.

Unlike some other members of the quinolone class, crystalluria and ocular toxicity were not observed in chronic safety studies with rats or dogs with either trovafloxacin or its prodrug, alatrofloxacin.

Quinolones have been reported to have proconvulsant activity that is exacerbated with concomitant use of non-steroidal anti-inflammatory drugs (NSAIDS). Neither trovafloxacin administered orally at 500 mg/kg, nor alatrofloxacin administered intravenously at 75 mg/kg, showed an increase in measures of seizure activity in mice at doses when used in combination with the active metabolite of the NSAID, fenbufen.

As with other members of the quinolone class, trovafloxacin at doses 5 to 10 times the human dose based on mg/kg or 1 to 5 times the human dose based on mg/m 2 produces testicular degeneration in rats and dogs dosed for 6 months.

At a dose of trovafloxacin 10 times the highest human dose based on mg/kg or approximately 5 times based on mg/m 2 , elevated liver enzyme levels which correlated with centrilobular hepatocellular vacuolar degeneration and necrosis were observed in dogs in a 6 month study. A subsequent study demonstrated reversibility of these effects when trovafloxacin was discontinued.

Hospitalized Community Acquired Pneumonia

Adult patients with clinically and radiologically documented community acquired pneumonia, requiring hospitalization and initial intravenous therapy, participated in two randomized, multicenter, double-blind, double-dummy trials. The first trial compared intravenous alatrofloxacin (200 mg once daily for 2 to 7 days) followed by oral trovafloxacin (200 mg once daily) for a total of 7 to 14 days of therapy to intravenous ciprofloxacin (400 mg BID) plus ampicillin (500 mg QID) for 2 to 7 days followed by oral ciprofloxacin (500 mg BID) plus amoxicillin (500 mg TID) for a total of 7 to 14 days of therapy. The second study compared intravenous alatrofloxacin (200 mg once daily for 2 to 7 days) followed by oral trovafloxacin (200 mg once daily) for a total of 7 to 14 days of therapy to intravenous ceftriaxone (1000 mg once daily for 2 to 7 days) followed by oral cefpodoxime (400 mg BID) for 7 to 14 days of total therapy with optional blinded erythromycin added to the ceftriaxone/cefpodoxime arm if an atypical pneumonia was suspected.

The clinical success rate (cure + improvement with no need for further antibiotic therapy) at the End of Treatment was 90% (311/346) and 90% (325/363) for TROVAN and the comparator agents, respectively. The clinical success rate at the End of Study (Day 30) was 86% (256/299) and 85% (283/334) for TROVAN and the comparator agents, respectively. All cause mortality (Day 1-35) was 2.45% (10/408) on TROVAN and 5.45% (23/422) on the comparator agents.

The following outcomes are the clinical success rates for the clinically evaluable patient groups by pathogen in these two studies:

Of the above patients with clinical failure at end of treatment or study, only one alatrofloxacin patient ( H. influenzae + S. pneumoniae ) and one ceftriaxone + erythromycin patient ( Legionella ) had a microbiologically confirmed persistent pathogen at the time of failure with no emergence of resistance in either study.

Nosocomial Pneumonia

Adult patients with clinically and radiologically documented nosocomial pneumonia participated in a randomized, multicenter, double-blind, double-dummy trial comparing intravenous alatrofloxacin (300 mg once daily for 2 to 7 days) followed by oral trovafloxacin (200 mg once daily) for a total of 7 to 14 days of therapy to intravenous ciprofloxacin (400 mg BID) for 2 to 7 days followed by oral ciprofloxacin (750 mg BID) for a total of 7 to 14 days of therapy with optional blinded clindamycin or metronidazole added to the ciprofloxacin arm if an anaerobic pneumonia was suspected. In subjects with documented Pseudomonas infection or methicillin-resistant S. aureus , aztreonam or vancomycin, respectively, could have been added to either treatment regimen.

The clinical success rate (cure + improvement with no need for further antibiotic therapy) at the End of Treatment was 77% (68/88) and 78% (79/101) for TROVAN and ciprofloxacin, respectively. The clinical success rate at the End of Study (Day 30) was 69% (50/72) and 68% (54/79) for TROVAN and ciprofloxacin, respectively.

The following outcomes are the clinical success rates for the clinically evaluable patient groups by pathogen:

Of the above patients with clinical failure at end of treatment or study, 2 alatrofloxacin patients ( S. aureus , P. aeruginosa ) and 4 ciprofloxacin patients (all P. aeruginosa ) had a microbiologically confirmed persistent pathogen at the time of failure. Three of the 4 ciprofloxacin patients with clinical failure and persistence had emergence of resistance with none on alatrofloxacin.

Complicated Intra-Abdominal Infections

Patients hospitalized with clinically documented, complicated intra-abdominal infections, including post-surgical infections, participated in a randomized, double-blind, multicenter trial comparing intravenous alatrofloxacin (300 mg once daily) followed by oral trovafloxacin (200 mg once daily) to intravenous imipenem/cilastatin (1g q8h) followed by oral amoxicillin/clavulanic acid (500 mg TID) for a maximum of 14 days of therapy. The clinical success rate (cure + improvement) at the End of Treatment was 88% (136/155) and 86% (122/142) for alatrofloxacin->trovafloxacin and imipenem/cilastatin->amoxicillin/clavulanic acid, respectively. The clinical success rate at the End of Study (Day 30) was 83% (129/156) and 84% (127/152) for alatrofloxacin->trovafloxacin and imipenem/cilastatin-> amoxicillin/clavulanic acid, respectively.

The following are the clinical success rates for the clinically evaluable patient groups by pathogen:

Of patients with a baseline pathogen and a clinical response of failure at the End of Study, 9 of 26 on TROVAN and 10 of 21 on imipenem/cilastatin had microbiologically-confirmed persistence of the baseline pathogen with no emergence of resistance in either group.

REFERENCES:

1. National Committee for Clinical Laboratory Standards, Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically--Fourth Edition; Approved Standard, NCCLS Document M7-A4, Vol. 17, No. 2, NCCLS, Wayne, PA, January, 1997.
2. National Committee for Clinical Laboratory Standards. Performance Standards for Antimicrobial Disk Susceptibility Tests--Sixth Edition; Approved Standard, NCCLS Document M2-A6, Vol. 17, No. 1, NCCLS, Wayne, PA, January, 1997.
3. National Committee for Clinical Laboratory Standards. Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria--Fourth Edition; Approved Standard, NCCLS Document M11-A4, Vol. 17, No. 22, NCCLS, Wayne, PA, December, 1997.

Rx only                                                        © 2000 Pfizer Inc

U.S. Patent No. 5,164,402

TROVAN is manufactured and distributed by:

Pfizer Roerig

Division of Pfizer Inc, NY, NY 10017

70-5328-00-6                                                 Revised April 2000