Chapter 4d Podiatric Infectious Diseases

4.4

Podiatric Infectious Diseases

Mark Kosinski, DPM

Assessment of the Patient with Infection In addition to performing the requisite history, review of systems and physical examination, it may be helpful include the following questions and observations when assessing a patient with infection.

History • When did the infection begin? Where and how was it acquired ? Distinguish between community and nosocomial (hospital acquired) infections. Past Treatment • What previous treatment if any, has the patient received? Has the patient been taking antibiotics?

Drug Allergies/Sensitivities • Does the have an allergy to penicillin or another antimicrobial agent? What form did the allergy take? Was it an anaphylactic reaction or delayed hypersensitivity ? How long ago did it occur and with what drug?

Review of Systems • Inquire about the presence of fever, chills, nausea, vomiting, diarrhea, weakness, malaise, and diaphoresis

Past Medical History • Including diabetes, HIV, IVDA, tuberculosis, STD’s , sickle cell anemia, renal or hepatic disease, and risk factors for infective endocarditis

Medications • Is the patient currently receiving antibiotic therapy or taking any medication which could affect immune response or mask the signs of infection (e.g., corticosteroids, cyclosporine)

Past Surgical History • Does the patient have implanted biomaterials, prosthetic joints, heart valves or shunts that might become secondarily infected ? Has the patient recently been hospitalized, putting them at risk for MRSA?

Social History • Ask about travel, jobs and pets Physical Examination Vital Signs • Include oral temperature, blood pressure, pulse and respiration Area of Chief Complaint • Note the presence and extent of cellulitis, lymphangitis, and regional lymphadenopathy (inguinal and popliteal). Note the odor and appearance of exudate and the extent and depth of the wound or ulcer. Lab Tests • Appropriate lab tests for a patient with infection include a CBC with differential, renal and hepatic function tests, ESR, blood glucose with glycosylated hemoglobin, urinalysis, X-rays, wound cultures and Gram’s stain. Consultations • Consult other medical services (eg., infectious diseases, internal medicine, vascular surgery) as needed

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Five Basic Principles of Antibiotic Selection and Empiric Treatment 1. Your antibiotic choice should be governed by the organisms you expect to find in a given situation 2. Distinguish between community and hospital acquired infections 3. Use an antibiotic with proven efficacy to the suspected or known organism(s) 4. Change or continue antibiotics based on culture results as soon as possible. Avoid prolonged empiric therapy 5. When sensitivities are known, choose the narrowest spectrum agent with the highest efficacy and the lowest toxicity

Odor, Color and Appearance as Clues to the Infecting Organism • • • • • • • •

Yellow pus S. aureus (coagulase positive Staph.) White pus S. epidermidis (coagulase negative Staph.) Green pus/exudate P. aeruginosa Dishwater pus Strep. group A (necrotizing fasciitis) Draining sinuses /granules* Actinomyces, Nocardia Fruity odor P. aeruginosa Foul, fetid odor Anaerobes (B.fragilis in diabetic foot) Wood’s Light flourescence – Coral red C. minitissimum – Green P. aeruginosa – Red Bacteroides melaninogenicus – Yellow Pityriasis versicolor * ‘sulfur granules’ are composed of colonies of Actinomyces or Nocardia surrounded by inflammatory cells. Distinguish actinomycosis from nocardiosis by culture and biopsy.

When you hear • • • • • • • • • • • • •

Paronychia Diabetic foot infection Sickle cell disease OM Puncture wound OM Post –op infection Post –op infection (implant) Human bites Cat bites Dog bites Burn wounds (acute) Burn wounds (chronic) IVDA Florists/Rose bushes • Fish tanks, pools • Salt / brackish water • Superficial Impetigo • Bullous Impetigo • Erysipelas • Web spaces • Scaulded Skin Syndrome

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Think S. aureus Polymicrobial (Staph., Strep.,B. fragilis) Salmonella P. aeruginosa S. aureus (MSSA/MRSA) S. aureus (MSSA/MRSA), S. epidermidis Eikenella corrodens. HIV, syphillis, hepatitis Pasturella multocida, Bartonella henselae DF-2 (Capnocytophaga canimorsus) nitially sterile, then S. aureus P. aeruginosa MRSA, P.aeruginosa, human oral flora (Eikenella corrodens) Sporothrix schenkii Mycobacterium marinum Vibrio vulnificus Group A Beta hemolytic Streptococci (Strep. Pyogenes) S. aureus Group A Beta hemolytic Streptococci (Strep. Pyogenes) Occasionally streptococci group C and G T. mentagrophytes, T. rubrum, C. minitissimum, Gram negative bacteria (e.g., pseudomonas, klebsiella, proteus) S. aureus

Empiric Therapy Empiric Therapy for Diabetic Foot Infections Your empiric antibiotic(s) should cover S. aureus, Group B Strep and in more serious infections, Gram negative bacteria and anaerobes (B. fragilis). It is therefore useful to choose an antibiotic based on the severity of infection

Mild Infection: • • • •

Local cellulitis (< 2 cm) No proximal spread No systemic S & S Normal labs

Contrary to previous belief that ALL diabetic infections were polymicrobial; these (mild infections) frequently are not. Cover for: • Staphylococcus aureus (MSSA/MRSA) • Increasing community-acquired MRSA • Group B Streptococcus Drugs used to kill S. aureus will almost always kill Strep.

MRSA • •

TMP/SMX Minocycline

MSSA • • • •

Cephalosporins (cephalexin, cefdinir) Amoxicillin/clavulanate Levofloxacin Clindamycin

Moderate to Severe Infection • Significant cellulitis (> 2 cm) – Gas • Proximal spread - lymphangitis • Constitutional S & S • Laboratory changes – Elevated WBC, left shift Although moderate to severe infections are commonly polymicrobial, S.aureus and Strep still predominate.

Organisms Found in Moderate to Severe Diabetic Infections: • • • • • • •

Staphylococcus aureus (MSSA/MRSA) Group B Streptococcus Gram-negatives Pseudomonas still uncommon as a “pathogen” Anaerobes B. fragillis Peptococcus, Peptostreptococcus

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Some Antibiotic Choices to Treat Moderate to Severe Infections: • b-lactamase inhibitor compounds – Ampicillin/sulbactam – Ticarcillin/clavulanate – Piperacillin/tazobactam • Imipenem/cilistatin, ertapenem • Clindamycin + a gram-negative agent

For MRSA • Linezolid ( plus gram negative agent + anaerobic agent) • Vancomycin ( plus gram negative agent + anaerobic agent)

Empiric Therapy for Mammalian Bite Wounds • Ampicillin/sulbactam (Unasyn). • Amoxicillin/ clavulante (Augmentin). • Ciprofloxacin/Clindamycin (Cipro/Cleocin) * *for pcn allergic patients

Empiric Therapy for Post-Operative Wound Infections S. aureus is the most commonly isolated organism in post operative wound infections. In addition, S. epidermidis is a common organism in post operative infections involving implants.

MRSA • TMP/SMX • Minocycline • For more sever infections, vancomycin or linezolid

MSSA • • • •

Cephalosporins (cefazolin, cephalexin, cefdinir) Amoxicillin/clavulanate Levofloxacin Clindamycin

Antibiotic Therapy for Methicillin Resistant Staph. aureus (MRSA) Differentiate Community Acquired MRSA (CA-MRSA) from Hospital Acquired MRSA (MA-MRSA) In general, CA-MRSA retains susceptibility to TMP/SMX and Tetracycline. HA-MRSA is resistant to TMP/SMX and tetracycline and like CA-MRSA is sensitive to vancomycin and linezolid. What both CA-MRSA and HA-MRSA have in common is the mec-A gene, making them resistant to all betalactam drugs.

MRSA Risk Factors • Patients in acute care and nursing facilities. • Individuals who have undergone previous antibiotic therapy • Those in proximity to patients infected or colonized with MRSA Patients with CA-MRSA may have no known risk factors.

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Antimicrobial Therapy for MRSA • • • • •

Vancomycin Tetracycline (minocycline/doxycycline) TMP/SMX Quinupristin/Dalfopristin Linezolid

Vancomycin (Vancocin) • • • • • •

Drug of Choice (DOC) for MRSA Use parenterally for systemic infections. Use orally for C. difficile colitis Concomitant use with an aminoglycoside can lead to additive nephrotoxicity Monitor serum concentration (peak and trough levels) and renal function (serum creatinine) Hemodialysis removes little or no vancomycin. Use 1g Q7-10 days in functionally anephric adults If red-man/red neck (anaphylactoid) reaction occurs, infuse slowly(over 60 minutes ) and pre-medicate with Benedryl. Administration of vancomycin 500mg q6h as opposed to 1g q12h will also minimize reaction • Poor bone penetration. Combine with rifampin for additive effect

Trimethoprim/Sulfamethoxazole (TMP/SMX) (Bactrim/Septra) • • • •

Do not use in patients with an allergy to sulfa drugs Most common adverse effect is skin rash which may limit its use Hematologic adverse reactions and bone marrow toxicity / neutropenia have also been reported Commonly used in the treatment of urinary tract infections and by patients with HIV disease for Pneumocystis carinii pneumonia (PCP) prophylaxis • Combine with Rifampin for additive effect.

Quinupristin/Dalfopristin (Synercid): • Active against MRSA/VRE. • Parenteral only. • Use within 30 minutes of reconstitution to prevent crystallization.

Linezolid (Zyvox) • • • •

Active against MRSA/VRE. Oral and parenteral forms available. High bioavailability after oral administration . In terms of blood levels; 600mg BID P.O. = 600mg BID I.V.

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TMP/SMX

Azithromycin

Ciprofloxacin

Clindamycin

Dicloxacillin

Cephalexin

Generic

500mg Q12h 875mg Q12h

1 DS Q12h

500mg day 1 then 250mg day 2-5

500mg Q12h 750mg Q12h

150mg-450mg Q6h

500mg Q6h

250mg-500mg Q6h

Usual Dose

Augmentin

Bactrim

Zithromax

Cipro

Cleocin

Dynapen

Keflex

Trade Name

(-)

(-)

(+)

(-)

(-)

(-/+)

(-)

(-)

MRSA

(-)

(+)

(+)

(+)

(+/-)

(+)

(+)

(+)

Gram +

(-)

(+)

(+)

(- )

(+)

(-)

(-)

(+)

Gram -

(-)

(-)

(-)

(-)

(+)

(-)

(-)

(-)

P. aeruginosa

(+)

(+)

(-)

(-)

(-)

(+)

(-)

(-)

Anaerobes

Oral Antibiotics

Amoxicillin/ Clav

Flagyl

(-) no activity

500mg Q8H

(+/-) fair

Metronidazole

(+) good

The above tables are intended only as a study guide and are based on podiatrically relevant pathogens within a given class. Definitive antibiotic therapy should be based on culture results and MIC’s.

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Vancocin Unipen

Unasyn Timentin

1g Q12 H

500mg - 1.5mg Q4-6H

1g Q8H

3g Q6H

3.1g Q6H

Vancomycin

Nafcillin

Aztreonem

Ampicillin/ Sulbactam

Ticarcillin/ Clavulanate

Maxipime

500mg Q6H

2g Q12H

Imipenem/ Cilistatin

Cefipime

(+) good

(-)

(-)

(-)

(-)

(-)

(-)

(-)

(+)

(-)

(-)

(+)

(+)

(+) (+)

(-)

(-) (except C. perfringens(+ /-))

(+)

(+)

(+)

(+)

(-) (-)

(-)

(-)

(-) (except C. difficile (+))

(+)

(-)

Anaerobes

(+)

(-)

(-)

(-)

(-)

P. aerugoinosa

(+)

(+)

(+)

(+)

(-)

(-)

(-)

(+)

Gram Negative

(-) no activity

(+/-)

(+)

(+)

(+)

(+)

(-)

(+)

(+)

(+)

(+)

Gram Positive

(+/-) fair

MRSA

The above tables are intended only as a study guide and are based on podiatrically relevant pathogens within a given class. Definitive antibiotic therapy should be based on culture results and MIC’s.

Primaxin

3.375g Q6H

Piperacillin/ Tazobactam Zosyn

Azactam

Cleocin

150 mg - 900mg Q6-8 H

Clindamycin

Ancef

Trade Name

1g Q6-8H

Usual Dose

Cefazolin

Generic

Parental Antibiotics

Antibiotic Caveats and Facts Ticarcillin/ Clavulanate • High sodium load (avoid in patients with CHF).

Imipenem/Cilistatin • Associated with dose-related seizures (use with caution in patients with seizure history). Cross reativity in patients with anaphylaxis to penicillin

Quinolones • Associated with tendinitis and tendon rupture. Studies involving the use of ciprofloxacin in children with cyctic fibrosis have shown that quinolones can be used with relative safety in this age group • Ciprofloxacin: Most active quinolone against P. aeruginosa • Levofloxacin : More active against gram positive aerobic cocci than ciprofloxacin

Clindamycin • Associated with C. difficile colitis. Active against Gram positive aerobes and anaerobes. Combine with a quinolone for gram negative coverage

Metronidazole • Has no aerobic coverage (do not use it as single agent therapy in foot infections) • Metronidazole has been shown to be more active against B. fragilis bloodstream isolates than clindamycin. Mild disulfuram reaction. Drug of choice for C. difficile colitis

Rifampin • An anti-tuberculous drug with activity against S. aureus. Rifampin should not be used alone since rapid resistance can develop. Use in combination with vancomycin for MRSA. May impart an orange color to the urine and cause a pink staining of soft contact lenses. May interfere with activity of oral contraceptives

Aminoglycosides • Nephrotoxic and ototoxic. Monitor serum levels with peaks and troughs. Try not to use for diabetic patients. There are better, albeit more expensive ways to cover gram negatives (e.g., quinolones, aztreonam)

Piperacillin/Tazobactam • Not recommended for monotherapy of P.aeruginosa at 3.375g q6h. (Med Lett Drugs Ther 1994 Nov 25;36(936):110). Many strains of P. aerugionsa have become resistant to the anti-pseudomonal penicillins by virtue of their hyperproduction of beta-lactamase

Cefepime • Fourth generation cephalosporin. Good activity against P.aeruginosa

Bactrim • Good bioavailability after oral administration. Can cause neutropenia. No anaerobic coverage

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Antibiotic Selection in Pregnant Patients / FDA Risk Categories Base your antibiotic choice on the FDA assigned risk category. Choose the drug from the safest category that will cover the infecting organism. A= safest / D= least safe.

FDA Category A NONE

FDA Category B • • • • • • •

penicillins, cephalosporins clindamycin aztreonam meropenem erythromycin/azithromycin metronidazole terbinifine

FDA Category C • • • • • •

imipenem/cilistatin quinolones trimethoprim/sulfamethoxazole vancomycin rifampin itraconazole

FDA Category D • aminoglycosides • tetracyclines

Ordering Lab Tests CBC/ Differential Acute infection is characterized by an elevated WBC count (absolute leukocytosis), as well as a shift to the left (increased number of immature or “band” cells)

Renal Function Tests • Evaluate renal function and dose adjust antibiotics accordingly – BUN – largely dependant on the hydration status of the patient and therefore of limited use. – Serum Creatinine - a more sensitive indicator of renal function than BUN. Serum creatinine may not accurately reflect the patient’s renal function in the elderly who may have decreased creatinine production. Creatinine clearance is a better measure. – Creatinine Clearance – most useful for antibiotic dose adjustment. Can either be had via a 24 hour urine collection or derived using the patient’s serum creatinine and the equation of Cockroft and Gault

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Estimating creatinine clearance using serum creatinine Modified equation of Cockroft and Gault Intended for ages 18-110, serum creatinine 0.6-7 mg/dl NOTE: This is the more popularly used version of the Cockroft-Gault formula at present. See literature for supporting data (e.g., Hutson P et al. Carboplatin Dosing in Obese Patients. Proc Am Soc Clin Oncol 2000, abstract 725). Ccr = (140-age) (weight in kg) For females multiply result by 0.85 72 X serum creatinine (1kg = 2.2 lbs) Note: the following antibiotics do not need dose adjustment for patients with renal impairment: amphoterecin B, azithromycin, ceftriaxone, clindamycin, nafcillin, trovafloxacin

ESR Non-specific. Although elevated in any inflammatory process, a patient with a non-healing foot ulcer and a significantly elevated ESR is suspicious for underlying osteomyelitis.

Wound, Bone and Blood Cultures Order aerobic, anaerobic, acid-fast and fungal cultures where clinically indicated.

Principles of Wound Cultures • Prep wound site to remove surface bacteria • Take a deep culture. Avoid contact with surrounding skin • Include tissue if possible (pus is a sub-optimal culture source since it contains mainly WBC’s and phagocytized bacteria) • Use proper transport media with respect to the organism being cultured • Rapid transport to lab

Principles of Bone Cultures With the possible exception of S. aureus, sinus tract cultures are rarely helpful in establishing the causative organism in osteomyelitis. The diagnosis of osteomyelitis rests with the isolation of the organism from bone • Sinus tract cultures are unreliable in predicting the infecting organism in bone • Bone biopsy is diagnostic • If possible, approach bone through uninfected tissue • Send bone for microscopic diagnosis. • Send bone for Gram’s stain • Order aerobic and anaerobic cultures • If clinically indicated, also order acid fast and fungal cultures and stains

Principles of Blood Cultures • Draw 2 sets 15 minutes apart (from different sites) If an organism grows from only one bottle, suspect contamination. • Drawing blood cultures on a fever spike may be of benefit

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Ordering Stains Results of cultures and MIC’s can take days (bacterial) to weeks (fungal and mycobacterial) to return. Ordering the appropriate stain/smear can provide a clue to the infecting organism in the interim. • Bacteria Gram’s stain KOH prep., PAS stain • Fungi • Mycobacteria Acid fast stain • Virus Tzanck smear

Gram’s Stain Terminology relates to appearance • Staphlococcus = cluster of berries • Streptococcus = twisted chain of berries

A Gram’s Stain That Reveals

Would be

Gram positive cocci in clusters Gram positive cocci in chains

Staphlococcus Streptcoccus

Coagulase Positive vs. Coagulase Negative Staph • Coagulase positive (invasive) • Coagulase negative (non-invasive)

Staph aureus Staph. epidermidis

Soft Tissue Infections Necrotizing Fasciitis Infection characterized by rapidly progressing necrosis and edema of subcutaneous fat and fascia. • Patient is acutely ill with fever, tachycardia and leukocytosis with bandemia • Extremity is initially hot, erythematous, edematous and exquisitely tender • Edema is hard and non-pitting and may extend beyond erythema • Skin becomes dusky with vesicles and bullae filled with deep purple fluid • Process spreads rapidly along subcutaneous tissue and undermines superficial fascia producing cutaneous anesthesia and eventually skin gangrene and slough • Grey, stringy, subcutaneous fascia, liquefaction necrosis and the presence of a thin, watery, foul smelling exudate (dishwater pus) are characteristic • Rapid progression may result in loss of limb or death • Bacteriology varies widely. No single organism is pathogneumonic. Aerobic and anaerobic bacteria have been identified including Streptococci group A, Clostridia spp. and Bacteroides spp. • Treatment is directed toward aggressive surgical debridement, broad spectrum antibiotics and stabilization of the patient medically

Common Cutaneous Viral Infections Herpes Zoster (Shingles) • Painful vesicles on an erythematous base in a dermatomal distribution. Etiology: reactivation of Varicella Zoster (chickenpox) virus (VZV). More common in elderly and immunocompromised patients. Herpes simplex (HSV) • Painful vesicles or pustules on an erythematous base, but no dermatomal distribution as in Herpes Zoster. HSV-1 typically affects above the waist, HSV-2 typically below Molluscum Contagiosum • Painless 3-6mm pearly papules with central umbilication. Etiology: Molluscum contagiosum virus (poxvirus). Spread by person to person contact

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Verruca • Etiology: Human Papilloma Virus (HPV). Distinguishing features include the presence of punctate black dots (thrombosed capillaries) and interruption of skin lines

Joint Infections Infectious Arthritis Any warm, swollen joint should be considered infected until proven otherwise. Antibiotic therapy should be guided by the patient’s age, the results of the synovial fluid analysis, culture and Gram’s stain.

Commonly Isolated Organisms • • • • •

Infants and young children (2-3 hours) • The immunocompromised patient To be effective, a prophylactic regimen must satisfy two criteria. First, the antibiotic must be active against the pathogen most likely to be encountered in a given situation and second, peak serum concentrations should be achieved at the time of inoculation. S. aureus is the most commonly isolated organism in post operative wound infections. For orthopedic procedures therefore, cefazolin (Ancef) has proven effective. In settings where MRSA is an important pathogen, vancomycin (Vancocin) should be used.

Trauma The severity of the fracture is the major determining factor as to whether or not infection will occur. Infection following fracture varies with the degree of injury • Grade I fracture • Grade II fracture • Grade III Fracture

0 - 9% 1% - 12% 9% - 55%

In the case of open fractures the length of antibiotic administration is proportional to the severity of the infection. • Prophylactic antibiotics for Type 1 and II fracture is maximally effective if given for no more than 24 hours after surgery. • For type III fractures continuation of antibiotics for 48 hours appears warranted assuming adequate soft tissue coverage after surgery. • The length of antibiotic administration should be extended if there appear to be signs and symptoms of infection. Although statistically S. aureus is the most common infecting organism in traumatic fractures, one must be cognizant of organisms which inhabit the environment in which the trauma was sustained . Antibiotic choices should be made accordingly. When instituting antibiotic prophylaxis for patients with distant prosthetic joints who undergo incision and drainage of infected tissue, base antibiotic selection on preoperative Gram’s stain and culture results or the anticipated organism. It is not necessary to use antibiotic prophylaxis to protect distant prosthetic joints who are undergoing clean orthopedic surgery, since bacteremia is unlikely to occur.

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Lower Extremity Surgery and Patients with HIV Regardless of their CD4 lymphocyte count, HIV-infected patients undergoing surgery have not been demonstrated to have a greater than usual rate of complication or a greater than usual rate of post-operative wound infection. T-cell mediated immunity is severely impaired in HIV infected patients, which is reflected by an increase in the number of intracellular pathogens such as viruses and non-pyogenic organisms as well as some extra-cellular organisms such as fungi and Pneumocystis, for which T-cell mediated immunity is the primary defense. Neutrophil mediated immunity on the other hand remains largely intact in HIV-infected patients. Infections for which the body’s primary defense is the T-cell mediated immunity (TB, parasites, mycobacteria) are thus more common in the HIV infected population. However, those infections for which the primary defense is the white blood cell or neutrophil (pyogenic bacteria such as Staph and Strep) are not significantly more common in non-neutropenic HIV patients. • Recommendations for perioperative surgical prophylaxis remain identical for HIV positive and HIV negative patients • The choice of antibiotic and dosage for a given infection is identical whether a patient is HIV positive or HIV negative and regardless of CD4 lymphocyte count • The use of markers such as viral load and CD4 lymphocyte count as an arbitrary qualification for surgery (e.g., CD4 “cutoff ” lines as a criterion) is both unwarranted and unsubstantiated in the literature

Common Causes of CD4 Lymphocytopenia (CD4 Count Less Than 300) • • • • • • • • •

Human immunodeficiency virus infection Mycobacterium tuberculosis infection Granulomatous disease (e.g., sarcoid) Malignancy Acute viral infection Immunosuppressive medication (corticosteroids, cyclophosphamide, cyclosporine) Pregnancy Malnutrition Aging

CD4 Counts at which Opportunistic Infections Occur

< 200/mm3 • • • • •

Extrapulmonary tuberculosis Toxoplasmosis Cryptococcosis Histoplasmosis Coccidiomycosis

4 /day. Diagnosis is by C. difficile toxin titers (from stool sample). Definitive diagnosis is by colonoscopy (visualizing the pseudomembranes on the bowel wall). Treatment of C. difficile colitis: • Orally administered Metronidazole. Parenteral metronidazole can also be used if patients cannot use oral route • Orally administered vancomycin (for patients fail metronidazole therapy) Vancomycin is poorly absorbed from the gastrointestinal tract resulting in high intraluminal concentrations. Nephrotoxicity from orally administered vancomycin can occur.

Tetanus • Symptoms of tetanus usually appear within of 3-21 days after inoculation but can occur between 1 day to several months • Localized tetanus- muscle spasm and rigidity begin local to the area of injury. May progress to generalized form • Generalized tetanus- muscle spasm begins with masseter and spreads to affect entire body • Clostridium tetani is an obligate anaerobe. Treat with metronidazole 500mg q6h or 1g q12h IV • Diazepam can be used to control muscle spasms.

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Prevention of Tetanus • Categorize wound as being either low or high risk • If wound is tetanus prone, begin prophylaxis Clean (Low Risk) • Clean incised wound • Superficial graze • Scald Tetanus Prone (High Risk)

• Wounds neglected > 24 hours • Any wound with one or more of the following: – Contact with soil, manure, compost – Puncture type wound – Gunshot wound – Infected wound

Open fracture Large amount of devitalized tissue Animal or human bite Foreign bodies

History of tetanus Immunization (doses)

Clean, minor wounds Td (Adult) TIG*

All other wounds Td (Adult) TIG

Uncertain or