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Cefaclororal.comCefaclor for Oral Suspension, USP
Mechanism of Resistance
describe the susceptibility profile of nosocomial and community-acquired pathogens. These reports should Resistance to cefaclor is primarily through hydrolysis aid the physician in selecting an antibacterial drug for of beta-lactamases, alteration of penicillin-binding To reduce the development of drug-resistant bacteria proteins (PBPs) and decreased permeability. and maintain the effectiveness of Cefaclor for Oral Pseudomonas spp., Acinetobacter calcoaceticus and Dilution Techniques Suspension and other antibacterial drugs, Cefaclor most strains of Enterococci (Enterococcus faecalis, Quantitative methods are used to determine for Oral Suspension, USP, should be used only to group D streptococci), Enterobacter spp., indole- antimicrobial minimum inhibitory concentrations treat or prevent infections that are proven or strongly positive Proteus, Morganella morganii (formerly (MICs). These MICs provide estimates of the suspected to be caused by bacteria.
Proteus morganii), Providencia rettgeri (formerly Proteus rettgeri), and Serratia spp. are resistant susceptibility of bacteria to antimicrobial compounds. to cefaclor. Cefaclor is inactive against methicillin- The MICs should be determined using a standardized resistant staphylococci. β-lactamase-negative, method (broth, agar, or microdilution)1,3. The MIC ampicillin-resistant strains of H. influenzae should values should be interpreted according to criteria Cefaclor, USP, is a semisynthetic cephalosporin be considered resistant to cefaclor despite apparent provided in Table 1.
antibiotic for oral administration. It is chemically in vitro to this agent.
designated as 3-chloro-7-D-(2-phenylglycinamido)- Diffusion Techniques 3-cephem-4-carboxylic acid monohydrate. The chemical formula for cefaclor is C H ClN O S•H O Quantitative methods that require measurement of and the molecular weight is 385.82.
Cefaclor has been shown to be active against zone diameters also provide reproducible estimates most strains of the following microorganisms both of the susceptibility of bacteria to antimicrobial in vitro and in clinical infections as described in the compounds. The zone size provides an estimate INDICATIONS AND USAGE section.
of the susceptibility of bacteria to antimicrobial compounds. The zone size should be determined Gram-positive Bacteria using a standardized test method2,3. This procedure Staphylococcus aureus (methicillin susceptible only) uses paper disks impregnated with 30 mcg cefaclor to test the susceptibility of microorganisms to Coagulase negative staphylococci (methicillin cefaclor. The disc diffusion interpretive criteria are After mixing, each 5 mL of Cefaclor for Oral Suspension susceptible only) provided in Table 1.
will contain cefaclor monohydrate equivalent to Table 1: Susceptibility Test Interpretive Criteria for
125 mg (0.34 mmol), 250 mg (0.68 mmol), or 375 mg (1.0 mmol) anhydrous cefaclor. The suspensions Streptococcus pyogenes (group A β-hemolytic also contain methylcellulose, sodium lauryl sulfate, Minimal Inhibitory
sucrose, and xanthan gum, FD&C Red No. 40, Microorganisms1,2 Concentration Diameter
Gram-negative Bacteria The color of drug powder in the dry powder state is Escherichia coli Streptococcus white to off-white. After reconstitution, it turns to a Haemophilus influenzae (excluding <1 2 >4 -- -- -- red suspension.
negative, ampicillin-resistant strains) 1 Susceptibility of staphylococci to cefaclor may be deduced from testing only penicillin and either cefoxitin or oxacillin Proteus mirabilis 2 Susceptibility of Streptococcus pyogenes to cefaclor Cefaclor is well-absorbed after oral administration to may also be deduced from testing penicillin fasting subjects. Total absorption is the same whether The following in vitro data are available, but their
the drug is given with or without food; however, clinical significance is unknown. At least 90
A report of Susceptible indicates that antimicrobial when it is taken with food, the peak concentration percent of the following bacteria exhibit an in vitro is likely to inhibit growth of the pathogen if the achieved is 50% to 75% of that observed when minimum inhibitory concentrations (MICs) less than antimicrobial compound reaches the concentrations the drug is administered to fasting subjects and or equal to the susceptible breakpoint of cefaclor. at the site of infection necessary to inhibit growth of generally appears from three-fourths to 1 hour later. However, the safety and effectiveness of cefaclor the pathogen. A report of Intermediate indicates that Following administration of 250 mg, 500 mg, and in treating clinical infections due to these bacteria the result should be considered equivocal, and, if the 1 g doses to fasting subjects, average peak serum levels has not been established in adequate and well- microorganism is not fully susceptible to alternative, of approximately 7, 13, and 23 mcg/mL, respectively, controlled trials.
clinically feasible drugs, the test should be repeated. were obtained within 30 to 60 minutes. Approximately This category implies possible clinical applicability 60% to 85% of the drug is excreted unchanged in Gram-negative Bacteria in body sites where the drug is physiologically the urine within 8 hours, the greater portion being concentrated or in situations where a high dosage of excreted within the first 2 hours. During this 8-hour drug can be used. This category also provides a buffer period, peak urine concentrations following the zone that prevents small uncontrolled technical factors 250 mg, 500 mg and 1 g doses were approximately from causing major discrepancies in interpretation. 600, 900 and 1,900 mcg/mL, respectively. The serum A report of Resistant indicates that the antimicrobial half-life in normal subjects is 0.6 to 0.9 hour. In Anaerobic Bacteria is not likely to inhibit growth of the pathogen if the patients with reduced renal function, the serum antimicrobial compound reaches the concentrations half-life of cefaclor is slightly prolonged. In those usually achievable at the infection site; other therapy with complete absence of renal function, the plasma should be selected.
half-life of the intact molecule is 2.3 to 2.8 hours. Excretion pathways in patients with markedly impaired renal function have not been determined. Standardized susceptibility test procedures require the Hemodialysis shortens the half-life by 25% to 30%.
use of laboratory controls to monitor and ensure the Susceptibility Test Methods
accuracy and precision of supplies and reagents used in the assay, and the techniques of the individuals Mechanism of Action
When available, the clinical microbiology laboratory performing the test.1,2,3 Standard cefaclor powder should provide the result of in vitro susceptibility should provide the following range of MIC values noted As with other cephalosporins, the bactericidal action of test results for antimicrobial drugs used in resident in Table 2. For the diffusion technique using the cefaclor results from inhibition of cell-wall synthesis.
hospitals to the physician as periodic reports that 30 mcg disk the criteria in Table 2 should be achieved.
3988 CefaclorPI-FNL.indd 1 Table 2: Acceptable Quality Control Ranges for
Positive direct Coombs' tests have been reported during treatment with the cephalosporin antibiotics. Cefaclor is contraindicated in patients with known It should be recognized that a positive Coombs' test Minimal Inhibitory Zone
allergy to the cephalosporin group of antibiotics.
may be due to the drug, e.g., in hematologic studies QC Strain
or in transfusion cross-matching procedures when antiglobulin tests are performed on the minor side or Escherichia coli in Coombs' testing of newborns whose mothers have BEFORE THERAPY WITH CEFACLOR IS INSTITUTED,
received cephalosporin antibiotics before parturition.
CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE
Haemophilus influenzae WHETHER THE PATIENT HAS HAD PREVIOUS
Cefaclor should be administered with caution in the HYPERSENSITIVITY REACTIONS TO CEFACLOR,
presence of markedly impaired renal function. Since Staphylococcus aureus CEPHALOSPORINS, PENICILLINS, OR OTHER
the half-life of cefaclor in anuria is 2.3 to 2.8 hours, DRUGS. IF THIS PRODUCT IS TO BE GIVEN
dosage adjustments for patients with moderate or TO PENICILLIN-SENSITIVE PATIENTS, CAUTION
severe renal impairment are usually not required. Staphylococcus aureus SHOULD BE EXERCISED BECAUSE CROSS-
Clinical experience with cefaclor under such HYPERSENSITIVITY AMONG β-LACTAM
conditions is limited; therefore, careful clinical Streptococcus ANTIBIOTICS HAS BEEN CLEARLY DOCUMENTED
observation and laboratory studies should be made.
pneumoniae AND MAY OCCUR IN UP TO 10% OF PATIENTS
As with other β-lactam antibiotics, the renal excretion WITH A HISTORY OF PENICILLIN ALLERGY.
of cefaclor is inhibited by probenecid.
IF AN ALLERGIC REACTION TO CEFACLOR OCCURS,
INDICATIONS AND USAGE
DISCONTINUE THE DRUG. SERIOUS ACUTE HYPER-
Antibiotics, including cephalosporins, should be prescribed with caution in individuals with a history Cefaclor is indicated in the treatment of the following SENSITIVITY REACTIONS MAY REQUIRE TREATMENT
of gastrointestinal disease, particularly colitis.
infections when caused by susceptible strains of the WITH EPINEPHRINE AND OTHER EMERGENCY
MEASURES, INCLUDING OXYGEN, INTRAVENOUS
Information for Patients
FLUIDS, INTRAVENOUS ANTIHISTAMINES,
Otitis media caused by Streptococcus pneumoniae, CORTICOSTEROIDS, PRESSOR AMINES, AND
Patients should be counseled that antibacterial drugs Haemophilus influenzae, staphylococci, and AIRWAY MANAGEMENT, AS CLINICALLY INDICATED.
including Cefaclor for Oral Suspension should only be used to treat bacterial infections. They do not Antibiotics, including cefaclor, should be administered Note: β-lactamase-negative, ampicillin-resistant
treat viral infections (e.g., the common cold). When cautiously to any patient who has demonstrated some (BLNAR) strains of Haemophilus influenzae should Cefaclor for Oral Suspension is prescribed to treat form of allergy, particularly to drugs.
be considered resistant to cefaclor despite apparent a bacterial infection, patients should be told that in vitro susceptibility of some BLNAR strains.
Clostridium difficile associated diarrhea (CDAD) has
although it is common to feel better early in the course of therapy, the medication should be taken Lower respiratory tract infections, including been reported with use of nearly all antibacterial
exactly as directed. Skipping dose or not completing pneumonia, caused by Streptococcus pneumoniae, agents, including Cefaclor for Oral Suspension,
the full course of therapy may (1) decrease the Haemophilus influenzae, and Streptococcus pyogenes USP, and may range in severity from mild diarrhea
to fatal colitis. Treatment with antibacterial
effectiveness of the immediate treatment and Note: β-lactamase-negative, ampicillin-resistant
agents alters the normal flora of the colon
(2) increase the likelihood that bacteria will develop (BLNAR) strains of Haemophilus influenzae should leading to overgrowth of C. difficile.
resistance and will not be treatable by Cefaclor be considered resistant to cefaclor despite apparent for Oral Suspension or other antibacterial drugs in vitro susceptibility of some BLNAR strains.
C. difficile produces toxins A and B which
in the future.
contribute to the development of CDAD.
Pharyngitis and Tonsillitis, caused by Streptococcus Hypertoxin-producing strains of C. difficile cause
Diarrhea is a common problem caused by antibiotics increased morbidity and mortality, as these
which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, Note: Penicillin is the usual drug of choice in the
infections can be refractory to antimicrobial
patients can develop watery and bloody stools (with treatment and prevention of streptococcal infections, therapy and may require colectomy. CDAD must
or without stomach cramps and fever) even as late including the prophylaxis of rheumatic fever. be considered in all patients who present with
as two or more months after having taken the last Cefaclor is generally effective in the eradication diarrhea following antibiotic use. Careful medical
dose of the antibiotic. If this occurs, patients should of streptococci from the nasopharynx; however, history is necessary since CDAD has been
contact their physician as soon as possible.
substantial data establishing the efficacy of cefaclor reported to occur over two months after the
in the subsequent prevention of rheumatic fever are administration of antibacterial agents.
Drug/Laboratory Test Interactions
not available at present.
If CDAD is suspected or confirmed, ongoing
Patients receiving cefaclor may show a false-positive Urinary tract infections, including pyelonephritis and antibiotic use not directed against C. difficile may
reaction for glucose in the urine with tests that use cystitis, caused by Escherichia coli, Proteus mirabilis, need to be discontinued. Appropriate fluid and
Benedict's and Fehling's solutions and also with Klebsiella spp., and coagulase-negative staphylococci electrolyte management, protein supplementation,
Skin and skin structure infections caused by antibiotic treatment of C. difficile, and surgical
There have been reports of increased anticoagulant Staphylococcus aureus and Streptococcus pyogenes evaluation should be instituted as clinically
effect when cefaclor and oral anticoagulants were Appropriate culture and susceptibility studies should be performed to determine susceptibility of the causative organism to cefaclor.
Carcinogenesis, Mutagenesis, Impairment of
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Cefaclor for Oral Studies have not been performed to determine Prescribing cefaclor in the absence of a proven or Suspension and other antibacterial drugs, Cefaclor potential for carcinogenicity, mutagenicity, or strongly suspected bacterial infection or a prophylactic for Oral Suspension should be used only to treat or impairment of fertility.
indication is unlikely to provide benefit to the patient prevent infections that are proven or strongly and increase the risk of the development of suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, Teratogenic Effects: Pregnancy Category B. they should be considered in selecting or modifying Prolonged use of cefaclor may result in the overgrowth Reproduction studies have been performed in antibacterial therapy. In the absence of such data, of nonsusceptible organisms. Careful observation of mice and rats at doses up to 12 times the human local epidemiology and susceptibility patterns may the patient is essential. If superinfection occurs during dose and in ferrets given 3 times the maximum contribute to the empiric selection of therapy.
therapy, appropriate measures should be taken.
human dose and have revealed no harm to the fetus 3988 CefaclorPI-FNL.indd 2 due to cefaclor. There are, however, no adequate focused trial to 2 in 8,346 (0.024%) in overall Cephalosporin-class Adverse Reactions
and well-controlled studies in pregnant women. clinical trials (with an incidence in pediatric patients Because animal reproduction studies are not always in clinical trials of 0.055%) to 1 in 38,000 (0.003%) In addition to the adverse reactions listed above that predictive of human response, this drug should be in spontaneous event reports. Signs and symptoms have been observed in patients treated with cefaclor, used during pregnancy only if clearly needed.
usually occur a few days after initiation of therapy the following adverse reactions and altered laboratory and subside within a few days after cessation tests have been reported for cephalosporin-class Labor and Delivery
of therapy; occasionally these reactions have antibiotics: fever, abdominal pain, superinfection, renal dysfunction, toxic nephropathy, hemorrhage, The effect of cefaclor on labor and delivery is unknown.
resulted in hospitalization, usually of short duration (median hospitalization = 2 to 3 days, based on false-positive test for urinary glucose, elevated postmarketing surveillance studies). In those bilirubin, elevated LDH, and pancytopenia.
requiring hospitalization, the symptoms have ranged Several cephalosporins have been implicated Small amounts of cefaclor have been detected in from mild to severe at the time of admission with in triggering seizures, particularly in patients with mother's milk following administration of single more of the severe reactions occurring in pediatric renal impairment when the dosage was not reduced. 500 mg doses. Average levels were 0.18, 0.20, 0.21, patients. Antihistamines and glucocorticoids appear If seizures associated with drug therapy occur, and 0.16 mcg/mL at 2, 3, 4, and 5 hours, respectively. to enhance resolution of the signs and symptoms. the drug should be discontinued. Anticonvulsant Trace amounts were detected at 1 hour. The effect No serious sequelae have been reported.
therapy can be given if clinically indicated (see on nursing infants is not known. Caution should DOSAGE AND ADMINISTRATION and OVERDOSAGE
be exercised when cefaclor is administered to a More severe hypersensitivity reactions, including nursing woman.
Stevens-Johnson syndrome, toxic epidermal necrolysis, and anaphylaxis have been reported To report SUSPECTED ADVERSE REACTIONS, contact rarely. Anaphylactoid events may be manifested FSC Laboratories, Inc. at 1-866-764-7822 or FDA at Safety and effectiveness of this product for use by solitary symptoms, including angioedema, 1-800-FDA-1088 or www.fda.gov/medwatch.
in infants less than 1 month of age have not been asthenia, edema (including face and limbs), dyspnea, paresthesias, syncope, hypotension, or vasodilatation. Anaphylaxis may be more common in patients with Signs and Symptoms -- The toxic symptoms following a history of penicillin allergy.
an overdose of cefaclor may include nausea, vomiting, Of the 3,703 patients in clinical studies of cefaclor, epigastric distress, and diarrhea. The severity of the Rarely, hypersensitivity symptoms may persist for 594 (16.0%) were 65 and older. No overall differences epigastric distress and the diarrhea are dose-related. several months.
in safety or effectiveness were observed between If other symptoms are present, it is probable that these subjects and younger subjects.
Gastrointestinal symptoms occur in about 2.5% of they are secondary to an underlying disease state, an patients and include diarrhea (1 in 70).
allergic reaction, or the effects of other intoxication.
Other reported clinical experience has not identified differences in responses between the elderly and Treatment -- To obtain up-to-date information about Onset of pseudomembranous colitis symptoms younger patients, but greater sensitivity of some the treatment of overdose, a good resource is your may occur during or after antibiotic treatment older individuals cannot be ruled out.
certified Regional Poison Control Center. Telephone (see WARNINGS). Nausea and vomiting have been
numbers of certified poison control centers are listed This drug is known to be substantially excreted by reported rarely. As with some penicillins and some in the Physicians' Desk Reference (PDR). In managing the kidney (see CLINICAL PHARMACOLOGY), and the
other cephalosporins, transient hepatitis and overdosage, consider the possibility of multiple drug risk of toxic reactions to this drug may be greater in cholestatic jaundice have been reported rarely.
overdoses, interaction among drugs, and unusual patients with impaired renal function. Because elderly Other effects considered related to therapy included drug kinetics in your patient.
patients are more likely to have decreased renal eosinophilia (1 in 50 patients), genital pruritus, function, care should be taken in dose selection, Unless 5 times the normal dose of cefaclor has been moniliasis or vaginitis (about 1 in 50 patients), and it may be useful to monitor renal function (see ingested, gastrointestinal decontamination will not and, rarely, thrombocytopenia or reversible DOSAGE AND ADMINISTRATION).
Protect the patient's airway and support ventilation Causal Relationship Uncertain - and perfusion. Meticulously monitor and maintain, within acceptable limits, the patient's vital signs, Adverse effects considered to be related to therapy CNS -- Rarely, reversible hyperactivity, agitation, blood gases, serum electrolytes, etc. Absorption with cefaclor are listed below: nervousness, insomnia, confusion, hypertonia, of drugs from the gastrointestinal tract may be dizziness, hallucinations, and somnolence have decreased by giving activated charcoal, which, in Hypersensitivity reactions have been reported in been reported.
many cases, is more effective than emesis or lavage; about 1.5% of patients and include morbilliform consider charcoal instead of or in addition to gastric eruptions (1 in 100). Pruritus, urticaria, and positive Transitory abnormalities in clinical laboratory test emptying. Repeated doses of charcoal over time Coombs' tests each occur in less than 1 in 200 patients.
results have been reported. Although they were of may hasten elimination of some drugs that have uncertain etiology, they are listed below to serve as Cases of serum-sickness-like reactions have
been absorbed. Safeguard the patient's airway when alerting information for the physician.
been reported with the use of cefaclor. These are employing gastric emptying or charcoal.
characterized by findings of erythema multiforme, Hepatic -- Slight elevations of AST, ALT, or alkaline Forced diuresis, peritoneal dialysis, hemodialysis, or rashes, and other skin manifestations accompanied phosphatase values (1 in 40).
charcoal hemoperfusion have not been established by arthritis/arthralgia, with or without fever, and as beneficial for an overdose of cefaclor.
differ from classic serum sickness in that there Hematopoietic -- As has also been reported with is infrequently associated lymphadenopathy and other β-lactam antibiotics, transient lymphocytosis, DOSAGE AND ADMINISTRATION
proteinuria, no circulating immune complexes, and leukopenia, and, rarely, hemolytic anemia, aplastic no evidence to date of sequelae of the reaction. Cefaclor is administered orally.
anemia, agranulocytosis, and reversible neutropenia Occasionally, solitary symptoms may occur, but do of possible clinical significance.
Adults -- The usual adult dosage is 250 mg every not represent a serum-sickness-like reaction. While
8 hours. For more severe infections (such as further investigation is ongoing, serum-sickness-like
There have been rare reports of increased prothrombin pneumonia) or those caused by less susceptible reactions appear to be due to hypersensitivity and time with or without clinical bleeding in patients organisms, doses may be doubled.
more often occur during or following a second (or receiving cefaclor and Coumadin® concomitantly.
subsequent) course of therapy with cefaclor. Such Pediatric Patients -- The usual recommended daily reactions have been reported more frequently in Renal -- Slight elevations in BUN or serum creatinine dosage for pediatric patients is 20 mg/kg/day pediatric patients than in adults with an overall (less than 1 in 500) or abnormal urinalysis (less than in divided doses every 8 hours. In more serious occurrence ranging from 1 in 200 (0.5%) in one infections, otitis media, and infections caused by 3988 CefaclorPI-FNL.indd 3 less susceptible organisms, 40 mg/kg/day are HOW SUPPLIED
recommended, with a maximum dosage of 1 g/day.
Cefaclor Oral Suspension, USP, is supplied in bottles with child-resistant caps as: 125 mg/5 mL strawberry flavor: Cefaclor for Oral Suspension, USP
NDC 13551-125-01 (150 mL size) 20 mg/kg/day
250 mg/5 mL strawberry flavor NDC 13551-250-01 (150 mL size) 1/2 tsp t.i.d.
375 mg/5 mL strawberry flavor 1/2 tsp t.i.d.
NDC 13551-375-01 (100 mL size) 40 mg/kg/day
After mixing, store in a refrigerator. Shake well before 1/2 tsp t.i.d.
using. Keep tightly closed. The mixture may be kept for 14 days without significant loss of potency. 1 tsp t.i.d.
Discard unused portion after 14 days.
Store dry powder at 20° to 25°C (68° to 77°F). [See B.I.D. Treatment Option — For the treatment of otitis USP Controlled Room Temperature].
media and pharyngitis, the total daily dosage may be divided and administered every 12 hours.
1. Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial Susceptibility Cefaclor for Oral Suspension, USP
Tests for Bacteria that Grow Aerobically; Approved Standard - Tenth Edition. CLSI 20 mg/kg/day
document M07-A10, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2015.
1/2 tsp b.i.d.
2. Clinical and Laboratory Standards Institute (CLSI). 40 mg/kg/day
Performance Standards for Antimicrobial Disk Diffusion Susceptibility Tests; Approved Standard – Twelfth Edition. CLSI document M02-A12, 1/2 tsp b.i.d.
Clinical and Laboratory Standards Institute, 1 tsp b.i.d.
950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2015.
Cefaclor may be administered in the presence of 3. Clinical and Laboratory Standards Institute impaired renal function. Under such a condition, (CLSI). Performance Standards for Antimicrobial the dosage usually is unchanged (see PRECAUTIONS).
Susceptibility Testing; Twenty-fifth Informational In the treatment of Supplement. CLSI document M100-S25. Clinical β-hemolytic streptococcal infections, a therapeutic dosage of cefaclor should and Laboratory Standards Institute, 950 West be administered for at least 10 days.
Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2015.
Directions for Mixing:
Add appropriate water volume as indicated in the Yung Shin Pharmaceutical Ind. Co., Ltd. following table in two portions to dry mixture in the Tachia, Taichung 43769, TAIWAN bottle. Shake well after each addition.
Each 5 mL (approximately one teaspoonful) will then FSC Laboratories, Inc. contain Cefaclor, USP, monohydrate equivalent to Charlotte, NC 28210 125 mg, 250 mg or 375 mg anhydrous cefaclor, respectively, as shown in the following table.
Revised: 09/15 13551125-1A Oversize bottle provides extra space for shaking.
Cefaclor for Oral Suspension, USP
125 mg/5 mL
250 mg/5 mL
375 mg/5 mL
3988 CefaclorPI-FNL.indd 4
13th Australasian Vertebrate Keven Drew Wellington, New Zealand 2-6 May 2005 Hosted by Manaaki Whenua Landcare Research PO Box 69, Lincoln 8152, New Zealand. www.landcareresearch.co.nz A PRACTICAL BAIT MARKER FOR BRUSHTAIL POSSUMS – WHISKER MARKING BY RHODAMINE B Penny Fisher and Louis Tremblay