Chapter 6: Infectious

Diseases
Specific Diseases
Principles of Antiinfective Therapy Antibiotics
Drug Fever
Specific Antimicrobial Therapy Surgical
Considerations
Necrotizing Infections
Osteomyelitis
Septic Arthritis
Mycology
Viral Diseases
Rickettsial Diseases
Protozoan and Metazoan Infections
 INFECTIOUS DISEASE
Specific Diseases
1. VIRAL HEPATITIS: types A, B, non-A, non-B, C, E, and delta
a. Hepatitis B, non-A and non-B cause chronic liver disease that can lead to
cirrhosis

NOTE* ALL HEALTH CARE WORKERS SHOULD BE INOCULATED AGAINST THE

HBV- IT IS NOW AVAILABLE AS A 3 PART INOCULATION, FOLLOWING A
SIMPLE BLOOD TEST CHECKING FOR HEPATITIS B ANTIBODIES

b. Hepatitis A (Infectious hepatitis) is common and occurs by oral fecal

contamination or ingestion of contaminated food
c. Hepatitis A is usually diagnosed by finding IgG anti-HAV within 2-3 weeks of
illness, and the lgG anti-HAV thereafter
d. Hepatitis B may be associated with a chronic carrier state and chronic liver
disease, with IV drug abuse and homosexuality being common risk factors
( 10% of these patients are asymptomatic and become carriers, they can
transmit the virus to others who can get liver disease)
e. Hepatitis non-A and non-B account for 90% of transfusion related hepatitis
f. Drug
ACETAMINOPHEN, HALOTHANE, ALPHAMETHYLDOPA, ISONIAZID, induced
DIPHENYLHYDANTOIN AND PHENOTHIAZINE hepatitis
by the
following:
IT IS TREATED BY THE WITHDRAWAL OF THE DRUG
g. ACETAMINOPHEN is widely used and can cause irreversible liver damage
when more than 10 grams is ingested (can cause more damage in the
alcoholic or malnourished patient)
h. N-ACETYLCYSTEINE given p.o. within 24 hours of ingestion of
ACETAMINOPHEN enhances the liver's ability to clear the metabolites and
prevent toxicity

2. AIDS: HIV
a. HIV is one of a number of RNA retroviruses possessing a unique enzyme,
REVERSE TRANSCRIPTASE, which allows the virus to synthesize DNA from
RNA or synthesize DNA backwards; as RNA viruses they can make DNA that
may interfere or incorporate into the DNA of the host cell
b. TARGET-THE IMMUNE SYSTEM:
i. HIV infection follows viral recognition of certain molecular receptors (CD-4)
on the surface of human cells, both the T4 lymphocyte and on the
macrophages and monocytes (This is the key cell surface glycoprotein which
the AIDS virus recognizes and renders those cells carrying this marker
susceptible to infection). As a consequence the HIV infection can lead to
immunodeficiency
ii. With depression of the circulation of the T-helper lymphocyte population,
host response is impaired to a variety of potential pathogens: bacteria,
mycobacteria, viruses, fungi and helminths
iii. It is known that 40-50% of individuals infected with HIV and having less
than 400/mm circulating T-helper cells will develop the manifestations of AIDS
within 2 years, 80-85% will develop manifestations of AIDS if their T-helper
lymphocyte count is less than 200/mm
iv. Also associated with depression of the T-helper lymphocytes, the natural-
killer (NK) lymphocytes' function are also disrupted (these NK cells are
involved in immune surveillance against neoplasms and virusinfected cells)
v. Also associated with depression of the T-helper lymphocytes is depression
of immunoglobulin (antibody) producing B-lymphocyte, which ultimately leads
to the body's decreased responsiveness to vaccines
c. TARGET -THE CNS: HIV also targets the central nervous system leading to a
subacute encephalitis (AIDS encephalitis)
d. CLINICAL MANIFESTATIONS: A classification for the clinical spectrum of HIV
for adults has been proposed by the C.D.C.: thinking of the potential
consequences of the virus infection on a time line
i. GROUP I- Includes people manifesting acute HIV, transient and selflimited,
characterized by fever, rash, malaise, lymphadenopathy. Incubation period 4-
6 weeks after exposure (can be longer). The illness is characterized by
serologic conversion to HIV (+ anti-HIV antibody test)
ii. Group II- Asymptomatic infection with a positive serology and virus culture,
a positive serology but no manifestations of CNS disease (called a Latent
state)
iii. Group III- Persistent generalized lymphadenopathy, palpably enlarged
lymph nodes (> 1 cm) at 2 or more extra-inguinal sites persisting for more
than three months in the absence of any other cause: May have other
manifestations of the disease
iv. GROUP IV- Other diseases; individuals in this group have one or more
significant immunodeficiency or CNS disease, divided into 5 .subgroups
according to manifestations:
 Subgroup A: Constitutional disease (fever, weight loss)
 Subgroup B: Neurologic disease (progressive dementia, peripheral
neuropathy and myelopathy)
 Subgroup C: Infectious diseases (pneumonia, histoplasmosis, herpes
simplex, cryptococcosis, et. al.)
 Subgroup D: Secondary cancers ( Kaposi's sarcoma, non-Hodgkins
lymphoma)
 Subgroup E: Other diseases (chronic lymphoid interstitial pneumonitis)
e. CLINICAL MANIFESTATIONS BY ORGAN SYSTEMS:
i. General- fatigue, weight loss, fever and sweats
ii. Dermatologic- rashes (particularly fungal), seborrheic dermatitis, psoriasis,
nail changes and pigmented lesions
iii. Pulmonary- unexplained cough and shortness of breath
iv. Head/ENT- persistent sinus congestion, sore throat, discoloration of the
oral mucosa and tongue
v. Gl- diarrhea
vi. Neurological- headaches difficulty comprehending, behavioral changes,
numbness or tingling
f. TESTING: Seroconversion to a positive HIV antibody test may occur from 4-8
weeks following the acute illness (fever, fatigue, diarrhea, weight loss, night
sweats, and generalized lymphadenopathy).
i. The ELISA (enzyme-linked Immunosorbant Assay) is the primary screening
test to detect the antibody to HIV-1
ii. The Western Blot (Immunoblot) test is used to confirm the validity of the
ELISA test.
iii. A new detection test called the Polymerase Chain Reaction (PCR)
demonstrates amplified proviral DNA in lymphocytes, months to years before
antibody can be detected by ELISA or Western Blot technologies

3. SYPHILIS: a contagious systemic disease caused by the spirochete

Treponema pallidum, characterized by sequential stages and by years of
symptomless latency
a. Primary syphilis: the primary lesion or CHANCRE appears within 4 weeks of
infection and can be seen on the penis, anus, rectum, the vulva and cervix in
women, and also on the lips, tongue and buccal mucosa
b. Secondary syphilis: cutaneous rashes ( of the palms and soles-macules,
papules or pustules- ranging in color from pink to pale red) appear within 6-
12 weeks after infection and most are florid after 3-4 months. Some patients
exhibit lymph node enlargement. There are constitutional symptoms of
malaise, headache, anorexia, joint pain and nausea. At this stage some
develop syphilitic meningitis
c. Tertiary syphilis: can be divided into benign tertiary syphilis of the skin
bone and viscera, cardiovascular syphilis and neurosyphilis. The typical lesion
is a GUMMA (a chronic granulomatous reaction that leads to necrosis and
fibrosis), appearing most commonly just below the knee, the upper trunk, the
face and the scalp, but can occur anywhere in the body
d. Tests:
i. VDRL: (a flocculation test where a reagin antibody in the patient's serum
reacts visibly with CARDIOLIPIN, the antigen). Reported as REACTIVE, WEAKLY
REACTIVE, BORDERLINE OR NON-REACTIVE
ii. FTA-ABS: fluorescent treponemal antibody absorption, MORE SPECIFIC
THAN THE VDRL
iii. Darkfield Microscopy: demonstration of the spirochete taken from
exudates
iv. Other tests: For secondary and tertiary syphilis can include, biopsy of
lesions, echocardiography and radiology, EKG and CSF
e. Treatment: Penicillin (for all stages) with a serum level of .03 IU/mL for 6-8
days for infectious syphilis.

NOTE* Treat as follows: Benzathine penicillin 1.2 million units IM in each

buttock (primary) with two additional injections Q 2 weeks of above 4.
(secondary). Benzathine penicillin 2.4 million units IM Q 1 week X 3
weeks (benign tertiary)
GONORRHEA: Caused by Gram (-) diplococcus, Neisseria gonorrhea. Has
arthritic and dermatological manifestations (hemorrhagic bullae).
a. Diagnosis: You must use a special collection kit for a C & S that generates
carbon dioxide, called a Jembec plate. Otherwise you must take your
specimen and plate it immediately on chocolate agar, since the organism is
so fastidious. Treatment of uncomplicated urethral gonorrhea is via
Ceftriaxone, 250 mg IM X 1 plus Vibramycin 100 mg BID X 7 days (there are
also other alternatives

5. MENINGITIS: Most bacteria cause an ACUTE SEPTIC MENINGITIS, but TB

and syphilis cause SUBACUTE MENINGITIS. Viral infections cause ACUTE
ASEPTIC MENINGITIS, while fungal infections and malignancies cause
SUBACUTE ASEPTIC MENINGITIS
a. Acute Septic (Bacterial) Meningitis: 3 bacteria account for 80% of all cases,
NEISSERIA MENINGITIDIS, H. INFLUENZA AND STREP PNEUMOCOCCUS (H. flu
occurs in most children > 1 yr and S. pneumo most common cause in adults)
b. Signs and symptoms: A sore throat can precede fever, headache, stiff neck
and vomiting which characterize ACUTE MENINGITIS. Adults and children
become desperately ill within 24 hours
c. Diagnosis: Since acute bacterial meningitis, especially meningococcal, can
be lethal in hours, accurate diagnosis and treatment are urgent, therefore
any unexplained fever in infants between age 3 months and 2 years of age
warrants close monitoring and, if necessary, lumbar puncture. When bacterial
meningitis is suspected, antibiotics should not await the results of diagnostic
tests.

NOTE* A petechial or purpuric rash can occur in generalized septicemia.

Check blood cultures, CT scan, lumbar puncture or any secretion or d.
serologic test looking for the bacteria or bacterial antigen
Treatment: Antibiotics as per culture and sensitivity, to continue 1 week after
fever subsides
e. Differential diagnosis: Subacute bacterial endocarditis (microbial infection
of the heart valves)

6. SUBACUTE BACTERIAL ENDOCARDITIS: A previous episode of infective

endocarditis, a history of rheumatic valvular disease, patients with congenital
heart lesions (Mitral valve prolapse + murmur) and prosthetic valves are high
risks for developing endocarditis infections. Therefore, should these patients
should be prophylaxed with antibiotics for clean podiatric surgery? According
to Warren Joseph, D.P.M., there are NO recommendations by A.H.A. for
prophylaxing in clean orthopedic surgery
a. Causative organism: Strep more common than Staph aureus
b. Signs and symptoms: Sudden. onset of fever, chills, weakness and often
times aching joints. Findings include petechiae of the oral mucosa and skin,
especially the trunk and painful fingertips and erythematous
lesions of the palms and soles (Janeway's lesions). The most common clinical
finding is a heart murmur
c. Diagnosis: Is by blood culture and echocardiogram (to see vegetations on
the valves). Obtain 6 different blood culture specimens at different fever
spikes
7. LYME DISEASE: This is a tick (Ixodes dammini) transmitted, spirochetal
(Borrelia burgdorferi) inflammatory disorder best recognized clinically by a
skin lesion, erythema chronicum migrans (Stage 1), red macule or papule
that expands often with a central clearing to as large as 50 cm.
Accompanying the skin lesion, or preceding it are malaise, fever, chills,
headache and stiff neck. Neurologic abnormalities (Stage 2) like Bell's palsy
and arthritis (Stage 3), especially the knees, can develop in patients within
weeks to months of the skin lesion.
a. Differential diagnosis: In children juvenile RA and adults Reiter's syndrome
and atypical RA
b. Treatment: In adults, tetracycline 250mg QID for 10-20 days and for
children and pregnant women, penicillin V 500 mg QID (early stage)

8. TETANUS: Tetanus is caused by an exotoxin (tetanospasmin) elaborated

by Clostridium tetani, a gram positive, anaerobic, bacillus. The toxin enters
the CNS along the peripheral motor nerves or may be blood borne to the
nervous tissue, and binds to the ganglioside membranes of nerve synapses.
Once fixed the toxin cannot be neutralized.
a. Signs and symptoms: Stiffness of the jaw, difficulty in swallowing,
restlessness, headache, fever, sore throat and later difficulty in opening jaws,
spasm of facial muscles with elevated eyebrows
b. Prognosis: Mortality is high in the young and old patient and drug abuser
c. Prophylaxis: At the time of injury, 0.5 mL of toxoid elicits a protective
antibody level in a previously immunized patient; this booster is not
necessary if is it known beyond doubt that the patient has received a booster
within the past 5 years. An inadequately immunized patient should be given
tetanus immune globulin (human) 250-500 u. IM depending upon the
wound potential. At the same time, the first of 3 0.5 mL doses of absorbed
tetanus toxoid should be given sub-cutaneously at another site.
The second and third doses are given at monthly intervals.

Tetanus Immunization Guidelines*

1. If the patient never immunized and the patient has a dirty wound:
a. TIG (tetanus immune globulin) 250 U IM and
b. dT (diptheria tetanus toxoid) IM
2. If immunized and the patient presents with a dirty wound
a. Give dT booster if the last booster was greater than 5 years in the past
3. Every adult should have dT boosters every 10 years

*Center for Disease Control recommendations

9. RABIES: Is an acute infectious disease of mammals, especially carnivores,

characterized by CNS irritation followed by paralysis and death. Rabid animals
transmit the infection by biting animals or humans. Rabies can also be
transmitted by exposure of a mucous membrane or fresh skin abrasion to
infected saliva.
a. Diagnosis: Examination of the infected animal's brain for Negri bodies, or
if the animal is healthy and when practical, observation of the animal by a
veterinarian for 10 days.
b. Prophylaxis: see guide to follow

POSTEXPOSURE ANTIRABIES GUIDE

Animal and Its Condition
SPECIES CONDITION AT TIME OF ATTACK TREATMENT OF EXPOSED HUMAN
Wild animal Regard as rabid unless RIG followed by HDCV
(skunk/fox) proven negative
Domestic dog/cat Healthy & available for None
observation
Escaped (Unknown) Consult with public health
officials
Rabid or suspected rabid RIG followed HDCV

NOTE* RIG= Human rabies immune globulin, gives passive immunization

HDCV= Human diploid cell virus, gives active immunization (Series of 5
IM deltoid area injections @ day 1,3,7,14 and 28)
c. Wound Care: The wound should be cleansed immediately and thoroughly
with a 20% solution of medicinal soft soap or 1 benzalklonium chloride. Deep
puncture wounds should be flushed not scrubbed, using a catheter and soapy
water (25 ga rubber angiocatheter needle on a large syringe). Do not
cauterize or suture the wound. For large defects, pack open. (This treatment
holds true for all bite wounds, except add Augmentin/tetracycline/Cipro to
cover prophylactically against sepsis)

PRINCIPLES OF ANTIINFECTIVE THERAPY

"The decision to institute antibacterial therapy requires a careful assessment
of the probability of infection; the likely cause of infection; the probable
susceptibilities of the infecting organism to the available antibiotic drugs; and
host factors likely to influence the presentation, clinical course, and outcome
of the infection. If infection is not currently present but the clinical
circumstances in the host suggest that the risk of infection is high,
PROPHYLACTIC antimicrobial therapy may be implemented. If infection is
suspected but not proved, EMPIRIC therapy designed to treat the most likely
pathogens is initiated, until an accurate diagnosis can be made. If the site
and causative organism are known then DEFINITIVE therapy can be
initiated".*

*Zier BG, Essentials of Internal Medicine in Clinical Podiatry, Philadelphia, Saunders, 1990, pg
327

1. INFECTION: is contamination above 105 bacteria per gram of tissue in

a healthy adult and as little as 102 in the presence of an artificial joint. A
developing coagulum begins to surround bacteria after 3 hours, protecting it
from antibiotic lavage and prophylactic antibiotic doses
 NOTE* Infection is a clinical diagnosis. It is not defined by some artificial lab
finding that most labs do not even do. Just because a contamination is
above 105 doesn't mean you cannot close an open wound. It is a clinical
evaluation, not a laboratory one. This numerical value (105) is only utilized
here as it has appeared on numerous board examinations

NOTE* There have been studies proving that 70% of all implants have slime
forming bacteria present in large numbers, yet there is no infection.
Therefore the value as mentioned 102 is only mentioned as a reference
point for the board examinations

a. Diagnosis: Is made by a combination of factors to include signs and

symptoms, prior therapy, medical history, allergies, social and travel history,
physical examination (includes vital signs) and laboratory diagnosis
i. Physical Findings: Warmth and erythema along the incision or wound with
possible exudates

NOTE* The 5 cardinal signs of infection are: RUBOR, TUMOR, DOLOR, CALOR,
and FUNCTIO LASEA

ii. Systemic signs consistent with fever > 100 degrees F or 37.7 C, with
lymphadenopathy, lymphangitis, shakes, chills and malaise

iii. Lab Studies- X-rays, Bilaterally (always serve as a base line for future
reference)

Gas in tissues indicates pathology (could also be H202 lavage, if utilized)

Osteomyelitis takes at least 10-14 days to show on x-ray
Bone scans/ Gallium scans/ Indium scans (IF OSTEO IS SUSPECTED)
CBC & Diff/ SMA 18-24/ ESR/ Urinalysis
Gram Stain (Blue/positive, Red/negative)
Aerobic/ anaerobic/ fungal/ acid fast cultures)
Blood cultures (when septicemia is suspected

NOTE* Anaerobic cultures should be obtained in the following circumstances:

Note* A lefta. shift
A putrid
is anodor from in
increase the wound
the number of immature PMN'S or band
b. A deep abscess, pain
cells. When the percentage of bands is greater without discharge
than 20 or when the
percentage of bands or segs together add up to 80, Gas
c. Significant tissue necrosis (gangrened. this formation
is considered a
e. Failure
shift to the left.NOTE* to recover
Infection,
Anaerobic pathogens
toxemia, bacteria in the
and hemorrhage aerobic
are very difficult culture
will cause a8shift
Gram
to culture evenstain
left. in the best of
f. The
Liver disease and failure
conditions. of the
megaloblastic infection
The 4 and
major to
iron respond
anaerobes
deficiency toanemias will cause anot active
antibiotics
are: that are
shift to theagainst
NOTE*
right anaerobes
A gram stain can be(most
a. Peptostreptococcus performed within 10 minutes and provides gross
common)
g.identification
Infection secondary
b. Peptococcusof the pathogen
to animal toorallow
human
for proper
bite selection of antibiotics. A
h.culture
Previousis most
therapy
c. Clostridium accurate
with amino
and alsoglycosides
checks the resistance of pathogens to the
i.antibiotics.
Black discoloration
However,
d. Bacteroides ofa blood
culture
containing
does not exudates
diagnose (mayan infection,
fluoresce that
red
is under
a
UV)
clinical finding.
 NOTE* For osteomyelitis, the most definitive diagnosis is by bone biopsy.
With an ascending cellulitis and no area of drainage, there is a less than
10% chance of obtaining a pathogen by injecting .5cc sterile saline
(without bacteriostatic agent) along the leading edge of the cellulitis and
reaspirating the solution back into the syringe and sending it for culture.
If septicemia is suspected, blood cultures should be ordered from 2
different sites at the start of a fever spike.
2. Indications for hospitalization:
a. Systemic manifestations (fever/shakes/chills, lymphangitis,
lymphadenopathy)
b. Debilitated host ( Diabetic, p.v.d., alcoholic, immuno-suppressive therapy,
burn patients)
c. Need for IV antibiotics (Resistant organism, risk of deep space infection,
deep space necrosis or wet gangrene)
d. Osteomyelitis (most times)
e. Need for extensive surgical debridement
f. Failure of outpatient therapy

3. Indications for consultations:

a. For medical management of systemic disease
b. Utilizing a toxic antibiotic
c. Gram negative septicemia
d. Patient on immuno-suppressive therapy
e. Patient with abnormal renal/hepatic function

4. Management of soft tissue post-op Infections:

a. Decide on hospital or outpatient therapy
b. Consider ID consult/ internal medicine consult/ vascular consult prn
c. Perform local wound care/release and remove sutures/ incision and
drainage as necessary
d. Send specimen for gram stain and aerobic/anaerobic/fungal/acid fast
cultures (as necessary)
e. Obtain other necessary lab studies
f. Begin antibiotics as per gram stain & clinical evaluation and judgement/
reevaluate as per C & S
g. Continue appropriate antibiotic at least 10 days (especially when treating
strep, to prevent post strep glomerulonephritis)

5. Preoperative antibiotics are indicated in the following

circumstances: Valvular disease (when indicated), surgery in the presence
of an artificial joint or the implantation of a new one, contamination,
prolonged procedure or extensive dissection, debilitated host and patients
with shunt
a. Consider using: Ancef 1 gm IV preoperatively (can also use postoperatively,
1 gram Q8H in 2 additional doses prn)
b. If penicillin allergic- then Vancomycin 500mg tot gm IV, or Clindamycin
300mg po pre-op
c. Prophylactic antibiotics in the diabetic: Postop infections in diabetics are
usually monomicrobial. Most common pathogens are Staph aureus, Staph epi,

Organism Morphology
 Gram Positive: Staphylococcus Cocci in grape-like clusters
Streptococcus Cocci In chains
Clostridium Bacilli (rods) with a "racquet shape"
Corynebacterium Rods In "Chinese characters"
 Gram Negative: Neisseria Diplococcus (usually
Intracellular)
Note* The current literature states that there is no significant difference in
Pseudomonas Slightly
postoperative infection rates between one dose,curved rod three dose or one
two dose,
Haemophilus/Pasturella Coccold rods
week of prophylaxis
E. Coll/Shigella/Serratla/
Enterobacter/Bacteroldes Straight rods
Strep pyogenes and Pseudomonas.
Best drugs are 1st gen. cephalosporins, vancomycin or clindamycin in the
penicillin allergic patient
d. Antibiotics should be administered no less than 5 minutes before inflation
of the tourniquet and no more than one hour before surgery.

6. Identification of organisms by morphology (Gram stain):

Antibiotics

The best antibiotic is the one that has the narrowest spectrum, the safest,
the cheapest
1. The Penicillins
a. Penicillin G: Parent compound introduced in the 1940's
i. Good gram(+) and weak gram(-) coverage
ii. Fallen out of favor since many resistant strains (Staph 100% Beta
lactamase producing)
iii. 1 mg PenG= 1667 units
iv. Available as Aqueous (10-30 million u/day) and Procaine (600,000 u Q1 2h)
b. Penicillin VK:
i. Used in severe erysipelas and rheumatic fever prophylaxis
c. Methicillin:
i. For PCN-ase resistant organisms
ii. IV form only
iii. Can cause thrombophlebitis
d. Oxacillin/Dicloxicillin/Cloxacillin/Nafcillin: (PRP's)
i. PCN-ase resistant
ii. Good gram(+) coverage
iii. Oral form can cause diarrhea
iv. Requires frequent dosing, Q4-6 hours
e. Ampicillin: Increased gram(-)coverage
i. Not PCN-ase resistant
ii. Used with UTI, typhoid fever and salmonella infections
iii. Used pre-op for endocarditis prophylaxis
iv. Used in combination with aminoglycosides for gram(-) septicemia
f. Carbenicillin: The original anti-pseudomonal penicillin
i. Can be combined with aminoglycoside for pseudomonas infection
ii. Not used much now since has high sodium content, hepatotoxic,
neurotoxic and causes bleeding disorders
iii. Oral form: Geopen (UTI's only)
g. Ticarcillin: A 4th generation penicillin active against pseudomonas
i. 2-4 times more potent than carbenicillin vs pseudomonas
ii. Has increased anaerobic activity
h. Piperacillin: As above, gram(+) 9 (-) activity
i. Azlocillin: As above but superior to ticarcillin/piperacillin vs pseudomonas
aeruginosa
i. Neurotoxic/Hepatotoxic
j. Mezlocillin (Mezlin): A 4th generation penicillin with good gram(-) and
anaerobic activity
i. Can be used for Pseudomonas/B.fragilis

NOTE* The adverse effects of the penicillins can manifest as hypersensitivity,

hematologic, renal, hepatic, G.l., and C.N.S. reactions.
a. Hypersensitivity (approaches 10%):
Type 1: anaphylaxis, laryngeal edema, accelerated urticaria
Type 2: Coombs positive hemolytic anemia
Type 3: serum sickness; urticaria after 72 hours
Type 4: contact dermatitis usually after accidental exposure
b. Hematologic:
Neutropenia: nafcillin/carbenicillin
Platelet dysfunction: carbenicillin
c. Renal:
Interstitial nephritis/cystitis: methicillin
Electrolyte imbalance: ticarcillin/carbenicillin/ penicillin G
d. Hepatic
SGOT elevation: oxacillin
e. G.1.
N.V.D.: amoxicillin/ampicillin
f. C.N.S.
Seizures (rare): penicillin G

2. The Clavulanates
a. Amoxicillin/clavulanate (Augmentin): Adds clavulanic acid to ampicillin
which inactivates the beta-lactamase enzymes:
i. PCN-ase resistant
ii. Spectrum of activity increased vs gram (-) to include E.Coli & Klebsiella,
also good Staph and Bacteroides coverage
iii. The oral drug of choice for cat, dog and human bites
iv. Dosed at 250-500 Q 8h (for other than endocard prophylaxis)
b. Ticarcillin/clavulanate (Timentin): Has greater gram(-) coverage than any
4th gen. penicillin
i. Has good gram(+) coverage and covers anaerobes well (i.e. B. fragilis)
ii. Good drug for initial therapy for moderate diabetic foot infections
iii. Has high sodium load/use cautiously in hypertensive-renal pt's
iv. Dosed at 3.1 Q 6-8h (3gm ticarcillin + 100mg clavulanate)

3. The Sulbactams
a. Ampicillin/ sulbactam (Unasyn):
i. Similar to Timentin but has much lower sodium load
ii. Adds sulbactam, a beta-lactam inhibitor
iii. 99% coverage against B.fragilis/not good against
pseudomonas and good against enterococcus
iv. Dosed at 1.5-3g Q 4-6h.

NOTE* Unasyn has better gram (+) coverage than Timentin, but weaker
gram (-) coverage 4.
The Tazobactams
a. Piperacillin/Tazobactam (Zosyn)
i. Similar to Timentin in coverage and spectrum
ii. Adds Tazobactum a Beta lactamase inhibitor
iii. Has greater activity than pipericillin
iv. Dosed @ 3.375 gm Q 6 hrs

5. The Cephalosporins
Semi-synthetic compounds derived from the mold, cephalosporum
acremonium. There is a cross reactivity with penicillin allergic patients from
5-20% depending upon the source. As a whole, these antibiotics
are well tolerated, non-toxic and broad spectrum. They are categorized in
generations, which define their spectrum.

As you go from first generation to third generation you INCREASE GRAM

NEGATIVE COVERAGE AND DECREASE GRAM POSITIVE COVERAGE. a.
1st generation:
i. Keflin (cephalothin), Keflex (cephalexin), Ancef (cefazolin), Cefadyl
(cephapirin), Anspor & Velocef (cephradine), Duricef (cephadroxil)
ii. ACTIVITY vs gram (+) cocci: S. aureus and epidermidis, Strep pyogenes and
pneumonia
iii. Activity vs gram (-): Proteus mirabilis, E. coil, Klebsiella pneumonia (PECK)
b. 2nd generation:
i. Mandol (cefamandole), Mefoxin (cefoxitin), Ceclor (cefaclor), Zinacef
(cefuroxime), Ceftin (cefuroxime axetil), Monocid (cefonicid), Cefotan
(cefotetan), Lorabid (loracarbef), Cefzil (cefprozil)
ii. ACTIVITY vs gram (+): is variable to Staph , still OK to Strep

NOTE* Zinacef® and Mandol® are better than 1st generation for Staph iii.
coverage
Activity vs gram (-): as with 1st generation (PECK) plus H. flu, Enterobacter &
Neisseria (HENPECK)
c. 3rd generation:
i. Claforan (cefotaxime), Cefobid (cefperazone), Cefizox (cefizoxime),
Rocephin (ceftriaxone), Fortaz (ceftazidime), Suprax (cefixime), Vantin
(cefprodoxime proxetil)
ii. ACTIVITY vs gram (+): variable to both Staph and Strep
iii. Activity vs gram (-): as with 2nd generation (HENPECK) plus Serratia,
Morganella, Providencia, Citrobacter and Pseudomonas

NOTE* ROCHEPHIN HAS THE LONGEST HALF LIFE OF ANY 3RD GENERATION
CEPHALOSPORIN, THEREFORE CAN BE DOSED AT ONCE A DAY.
FORTAZ and CEFOBID HAVE THE BEST ACTIVITY AGAINST PSEUDOMONAS.
METHICILLIN RESISTANT STAPH AS WELL AS GROUP D STREP
(ENTEROCOCCI) ARE RESISTANT TO ALL CEPHALOSPORINS

NOTE* Probenecid 500 mg QID blocks tubular secretion doubling the

antibiotic concentration
NOTE* The topof8penicillin
questionsand
andcephalosporins
answers about cephalosporins:
1. Are the 1st generation cephalosporins more effective against grampositive
organisms than 2nd or 3rd generation cephalosporins? The most commonly
used 1st generation cephalosporin is cefazolin. This drug is excellent against
group A streptococci, pneumococci but it less effective against these gram
positive organisms than some of the 2nd and 3rd generation cephalosporins.
3rd generation cefotaxime, ceftizoxime, and ceftrriaxone, are more active
against pneumococci and some hemolytic and non hemolytic streptococci
than the first generation cephalosporins. These 3rd generation
cephalosporins inhibit resistant streptococcus pneumoniae as compared to
1st and 2nd generation cephalosporins.
 2. Why do cephalosporins not inhibit enterococci? Enterococci to not bind to
cephalosporins adequately. Enterococci produce a f-lactamase which makes
a cult wall to enter. Enterococcal superinfection is more common after
cefriaxone or 2nd generation cefuroxime.
3. What is the best way to administer Rocephin? A 2g. dose exceeds the
ability of the drug to bind to protein, therefore, more drug reaches the
tissues during a single 2g. dose than 1g. dose given in two doses.
4. Which of the cephalosporins are effective against Pseudomonas
aeruginosa? Ceftazidime has the highest activity of all the cephalosporins.
Also cefoperazone has activity against many P. aeruginosa but must be given
on a 6 hour interval.
5. Can cephalosporins be used in patients who are allergic to penicillin?
Cephalosporins may be administered to patients who have hat only
cutaneous reactions to penicillin. Anyone who has hat anaphylaxis to
penicillin should be skin tested with the breakdown products of penicillin
prior to any cephalosporin administration, ant if no wheal or flare it would be
safe to administer. Most reactions occurred during the 1960's when
penicillins ant cephalosporin were packaged in the same plant, which
probably caused cross contamination. It is also possible to be allergic to
cephalosporin ant not to penicillins.
6. Can children with osteomyelitis be treated with oral cephalexin?
Cephalexin has excellent absorption ant may be used to treat
Staphylococcus aureus osteomyelitis in children. Cephalexin produces very
high blood levels ant is well tolerated by children, Studies show that 4-6
weeks of this therapy is as effective as parenteral therapy.
7. Which cephalosporins inhibit anaerobes? Clinical studies show that
ceftizoxime ant ceftoxitin are both equally effective against anaerobes which
cause human infections. Those cephalosporins totally ineffective against
anaerobes are ceftriaxone ant ceftazidime.
8. What would be the 1st choice for meningitis at present? When dealing with
Neisseria meningitis in the U.S., penicillin is still effective. If the meningitis is
caused by H. influenza or by S. pneumoniae, the choice of therapy would be
cefotaxime or ceftriaxone. In the newborn cefotaxime combined with an
amino glycoside toes not cause the alteration in gut flora that ceftriaxone
toes. For S. marrewscens ant Acinobacter, ceftizoxime is the 3rd generation
cephalosporin of choice. Ceftazidime is useful in treating meningitis caused
by P. aeruginosa.

6. Other Beta-Lactams:
a. Imipenem/Cilastatin (Primaxin): Is an extremely potent antibiotic with the
broadest spectrum of an available beta lactam including anaerobic coverage/
most expensive antibiotic on the market. Cilastatin is added to prevent renal
hydrolysis (destruction of imipenem)
i. May be the drug of choice in severe/limb threatening diabetic infections ( as
initial therapy) other than clinda/genta/ampi
ii. Major therapeutic use for Gram (+) cocci and aerobic gram (-) bacilli
iii. A 3% cross sensitivity with penicillin allergic patients
Dosed at 0.5-1 gram Q 6h IV up to 4gm/day
b. Azreonam (Azactam): Is ONLY effective against gram (-) aerobes, including
P. aeruginosa
i. Can be combined with clindamycin in penicillin allergic patients when
gram(+)and anaerobes are suspected

7. Quinolones:
a. Ciprofloxacin (Cipro):
i. Its main benefit is it's p.o. gram (-) coverage
ii. Can be used for methicillin resistant staph but should be combined with
rifampin (300 mg BID) in the treatment of these infections
iii. Contraindicated in its use with children as it can cause cartilage
degeneration
iv. Can be combined with clindamycin (Cleocin) or metronidazole (Flagyl) in
the treatment of diabetic foot infections
v. Oral therapy for osteomyelitis when caused by Pseudomonas
vi. Rarely a first line antibiotic
b. Ofloxacin (Floxin):
i. As with the above, but with better gram (+) coverage
ii. Dosed for soft-tissue infections at 400 mg Q 12 h

8. Aminoglycosides:
a. Streptomycin: (used in treatment of TB)
b. Kanamycin (used as an irrigant)
c. Gentamycin: used with methylmethacrylacte beads (PMMA) for
osteomyelitis and in triple antibiotic therapy for serious infections
d. Potentially ototoxic in patients with renal problems

NOTE* Gentamycin is a good drug for use with PMMA because of its good
water solubility, heat stability, and broad antibacterial spectrum. Most
studies have fabricated PMMA beads utilizing 1-2 g of antibiotic powder
to 40-60 g of PMMA
d. Tobramycin (less ototoxic than gentamycin)
e. Amikacin (reserved for serious infections against aminoglycoside resistant
organisms)
f. As a group these antibiotics have well documented toxicities
(ototoxicity/hepatotoxicity). g. They are essentially anti-gram negative
agents, but do have gram positive coverage. When using these antibiotics it
is beneficial to, have an ID consult and you should perform peak/trough
serum levels as well as creatinine clearance and BUN tests (if BUN elevated
increase time span between doses or lower the dose)
NOTE* Aminoglycosides (gentamycin/tobramycin) must be monitored to keep
the peak level just below 10 micrograms/ml and the trough level below 2
micrograms/ml and Amikacin peak at 20-30 µ/ml and trough less than 10
µ/ml. The peak should be drawn within 30 minutes after infusion of the drug
and the trough level should be determined by drawing another blood sample
15 minutes prior to the next dose. The calculated dose of aminoglycosides
should be given Q 12 or 24 h (never Q 8)

NOTE* Two techniques can be used to change the dose of amnoglycosides

when inappropriate levels are found:
a. Raise or lower the amount of the dose
b. Increase or decrease the time interval
So…. if the peak is high and trough is normal: decrease the amount
if the peak is low and the trough normal: increase the amount
if the peak is normal and trough high: increase the time interval
if the peak is high and trough high: decrease the dose/increase
the time*
Joseph WS Handbook of Lower Extremity Infections, Churchill Livingstone, N.Y., 1990, pg. 182

9. Other antibiotics:
a. Vancomycin:
i. Indicated in penicillin allergic patients or those patients needing coverage
against gram (+) organisms, including methicillin resistant Staph
ii. It is possibly nephrotoxic and should be monitored carefully
iii. Red neck syndrome occurs if infused too quickly (not an allergy)/severe
hypotension can result
iv. Oral form is for pseudomembranous colitis only

NOTE* Peaks and troughs for vancomycin can be done. The peak is 20-30,
and the trough is <10

b. Clindamycin:
i. It is used extensively for anaerobic infections and in the penicillin allergic
patient for gram (+) coverage
ii. Can cause pseudomembraneous colitis
c. Tetracycline:
i. A broad spectrum antibiotic used for rocky mountain spotted fever,
Lyme disease, and H. pylori infection
ii. To be avoided in children and pregnant/ nursing mothers (brown
teeth)
d: Metronidazole (Flagyl):
i. An amebicidal drug also with excellent anaerobic coverage
ii. Can be combined with Cipro for more complete coverage
e. Erythromycin, clarithromycin (Biaxin), azithromycin (Zithromax)
Drug Fever
Fever is considered to be drug induced if no other infections or noninfectious
cause is present on the basis of clinical or laboratory evidence, if there is no
known underlying disease or condition, if the temperature elevation is
temporarily associated with the administration of a "sensitizing" medication
and if the fever disappears within 72 hours of discontinuation of the
medication.

The most reliable diagnostic clue is a relative bradycardia or

PULSE/TEMPERATURE DISSOCIATION in patients with 102 degrees F or above.
This pulse/temperature dissociation is unreliable in neonates, patients on
cardiac medications and patients with systemic diseases
accompanied by bradycardia. The treatment is to discontinue the causative
agent and avoid antipyretics.

Specific Antimicrobial Therapy

1. Gram (+) cocci (Penicillinase resistant): When a gram stain report is
received and initial therapy is to be started prior to receiving a C & S the
following should be considered due to the increasing number of beta-
lactamase organisms: Dicloxicillin 500 mg qid p.o., Nafcillin 1 gm IV Q6h,
Ancef 1 gm IV Q8h, Duricef 500mg bid, Timentin 3.1 gm Q6h IV and Unasyn
1.5-3.0 gm Q6h IV

2. Gram (+) cocci + penicillin allergy: Vancomycin 500mg or 1 gm Q6 and

Q1 2 H IV or Clindamycin 300 Q 6h po, Erythromycin 500 mg Q6h po

3. Methicillin (nafcillin/oxacillin) resistant gram (+) Staph: Vancomycin

500 mg Q 6h IV or 1 gm Q12h, Cipro 500 Q 12h po + Rifampin 300 mg Q1 2h
po (Rifampin synergizes the anti-gram (+) effect of Cipro when in
combination with it), Minocycline, Trimethoprim/sulfa

4. Gram (-): When a gram stain is received and initial therapy is to be started
prior to a C & S the following should be considered: Cipro 750 mg Q1 2h,
Azactam 1 gm Q8h IV, Gentamicin 3-5 mg/kg _IV following a loading dose,
Timentin and Fortaz 1-2 gms Q8h IV, Zosyn (tazobactam/piperacillin) 3.375
gm Q6 IV

5. Anaerobic coverage: Flagyl 500 mg Q8h po, Clindamycin 600-800 mg

Q8h IV or 300 mg bid-tid po, Primaxin, Timentin, and Unasyn

6. Antipseudomonal coverage: 4th generation penicillin (in combination

with another antibiotic), Fortaz 1-2 gm Q 8h, Azactam 1 gm Q8h, Gentamycin
3-5 mg/kg IV following a loading dose, Cipro 750 mg Q 12h

7. Antifungal coverage: Diflucan 100 mg od, Amphotericin B (very severe

side effects), Ketoconazole (Nizoral), Griseofulvin, and Sporanox 100mg
8. Antihelminthic Coverage: Thiabendazole (Mintezole) for cutaneous larva
migrans and hook worms, and Gamma Benzene Hexachloride (Kwell) for
parasitic skin infestations caused by scabies.

9. Pregnancy: Antibiotics that are probably safe to use are aztreonam,

cephalosporins, erythromycins (not estolate), and penicillins. However,
conversely, the antibiotics that are definitely not safe are the tetracyclines
and metronidazole. Always check with a patient's physician before giving
antibiotic to a pregnant women

NOTE* When administering antibiotics to females on birth control pills, you

must advise them that the activity of these medications are reduced and
that
they must utilize some other form of birth control during the time the
antibiotics are utilized.
P.S. Document that you said this in your chart

Note* MIC is measured in microgram per milliliter, the amount of antibiotic

needed to inhibit a specific organism and each organism will have its own
MIC to a given antibiotic
Note* The dosage for children is calculated based on age and body weight
according to Young's Rule, Clark's Rule and Cowling's Rule (see
anesthesia section)

Note* Adjusting the dosage of antibiotics in patients with compromised renal

function is based on a calculation called the Estimated clearance of
Creatinine (ml/mm) is as follows:
ECC (men)= (140-age) X weight (kg)
Creatinine concentration (mg/dl) X 72
ECC (women)= ECC (men)x 0.9

Surgical Considerations
Probably the single most important factor in the control of a postoperative
infection is local care of the wound. Unless all areas of abscess formation and
pus are drained and devitalized tissue excised the adjunctive therapy of moist
dressings, antibiotics etc., will be of little value. The exception to this is a
rapidly ascending cellulitis without areas of abscess formation in which
surgical debridement would be of no value.
1. Outline of General Surgical Principles: try not to use tourniquets, try
using regional anesthesia and not local anesthesia which can spread the
infection:
a. Sterile skin prep of foot
b: If a post-op infection, release all skin sutures
c. Explore the extent and depth of the infection, breaking up any loculations if
present, not extending into uninvolved areas
d. If the infection has gone below the subcutaneous layer explore and remove
any deep sutures or necrotic tissue, opening the wound to the deepest
portion of the infection
e. If the infection penetrated the joint capsule, the capsule must be opened, if
an implant is used it must be removed, the bone and cartilage must be
carefully inspected to determine the involvement
f. If an infection extends proximal and distal to a joint both the proximal
phalanx and metatarsal neck must be explored
g. If osteotomies have been done external fixation devices should be
removed
h. Once the extent of the infection is determined all devitalized soft tissue
and bone must be removed
i. Samples of deeper tissue and bone, if excised, should be submitted to
pathology for microscopic .examination as well as to microbiology for culture
and sensitivity tests
j. All implant material when removed should be sent to microbiology for
culture and sensitivity tests in order to isolate organisms which may be firmly
attached to the device and not found within the soft tissues k. The wound
should then be copiously lavaged with large volumes of 1% Betadine solution
followed by sterile saline or Ringer's lactate
l. The wound should be packed open with 1/4 or 1/2 inch iodoform gauze for
hemostasis and drainage and covered with gauze soaked in sterile saline or
Ringers lactate. When this dries it acts as a mechanical debriding agent
m. Immobilize and elevate the extremity
n. Keep extremity warm (can use Microtemp heating unit at 102°F)
o. Post surgically, the packing should be changed on a daily basis, and as the
wound starts to granulate less and less packing is necessary p. When
granulation tissue has completely filled the defect, closure of the wound is
attempted, however, for small to moderate surface defects, delayed primary
closure with skin adhesive strips to gradually bring the skin edges together is
attempted within three days after surgical debridement
q. If repeated cultures are negative and clinical appearance of the wound is
clean and well granulated, then the patient can return to the operating room
for irrigation and resuturing of the wound, which is attempted within 4-5 days.
This type of delayed primary closure should be avoided if the defect is large
and/or if the suture closure places excessive tension on the wound
r. If the defect is large the patient may undergo skin grafting when conditions
are right

Necrotizing Infections
The classification of necrotizing infections is difficult. Prompt and oftentimes
empirical medical and surgical therapy must be initiated to save life and limb.
Even with early intervention the rate of amputation and mortality is high, with
all of these patients having some underlying predisposition: trauma, surgery,
burns, malignancy, diabetes mellitus, immunosuppression, human bite
wounds, injection injuries, puncture wounds and PVD.
1. Necrotizing Fasciitis: Widespread necrosis of subcutaneous tissue
YOU MUST TREAT THIS WITHIN 48 HRS
a. Signs and Symptoms:
i. Fever, tachycardia, anemia, shift left and > bilirubin
ii. Hot/edematous/indurated/erythematous extremity
iii. The skin is shiny and smooth with vescicles & bullae filled with a
reddish-brown fluid
iv. Cutaneous anesthesia
v. Later: Tissue slough with grey necrotic subcutaneous fat and fascia b.
Causative organisms- Strep predominates
c. Diagnosis:
i. Extensive necrosis of the superficial fascia
ii. Toxic reaction/altered mental states iii. Absence of muscle involvement
iv. Absence of clostridium as the primary organism
v. No major vascular occlusion is present
d. Differential diagnosis- Lymphangiitis, Clostridial gas gangrene,
synergistic (the aerobes help the anaerobes proliferate) necrotizing
fasciitis/cellulitis and progressive bacterial synergistic gangrene
e. Treatment:
i. Stabilize the patient medically
ii. Penicillin/Gentamycin/Clindamycin or Primaxin
iii. Aggressive incision and drainage with multiple incisions
iv. Daily irrigation and packing

2. Synergistic necrotizing cellulitis/fasciitis is closely related to

necrotizing fasciitis, with a pathogenesis related to diabetes and obesity,
however this condition involves the entire muscle compartment resulting in
muscle necrosis. There are systemic manifestations with presence of the
reddish-brown "dishwater" pus. The gram stain is mixed with gram(+) & (-)
and there is a mixed aerobic & anaerobic infection (Bacteroides/
Peptococcus). The prognosis is poor with amputation a probability.

3. Clostridial Myonecrosis is also known as gas gangrene or clostridial

myonecrosis. It can present itself after injury, bums or trauma. There is a
tense swelling of the skin with a reddish-brown drainage containing gas
bubbles. There is the appearance of gas on soft tissue x-ray. The muscles
undergo necrosis and exhibit a color change to a reddish-purple. Clostridium
perfringens is usually the causative organism. The diagnosis can be made by
gram stain and Fluorescent Antibody Test. Prognosis and treatment as above,
with massive I & D and IV antibiotics (Penicillin).

4. Nonclostridial Myonecrosis is similar to the aforementioned but slower

to progress. The causative organisms can be anaerobic Strep
(Peptostreptococcus) or a combination of aerobic and anaerobic organisms
(synergistic). Treatment is similar to that of all necrotizing infections.

Osteomyelitis
1. Definitions:
a. Osteomyelitis- infection of bone (chronic OM & acute OM, the distinction of
which will determine treatment regime)
b. Sequestrum- dead necrotic bone separated from the affected bone
c. Involucrum- a chronic process where new bone is laid down around dead
bone
d. Cloaca- an opening in along the cortex from where the pus drains
e. Rarefaction- localized loss of bone density (earliest radiological finding
when 30-50% of the osseous mineralization has been lost)
f. Bone abscess ( Brodie's abscess)- localized focus of infection within bone
usually found in the metaphyseal region of tubular bones, but can be
occasionally found in the diaphysis (Chronic/subacute OM)
f. Chronic Sclerosing Osteitis (Garre's)- a low grade infection causing sclerotic
reaction without destruction or sequestration

2. Classifications:
a. Hematogenous (AHO)- a form of OM caused by spread of bacteria via the
bloodstream, originating within cancellous bone, which will result in
radiographic findings that start inside the bone and eventually work out to the
cortex and periosteum. Seen mostly in the metaphyseal region in children
with open epiphyseal plates, occurring most commonly in the calcaneous
and femur. In adults it is most commonly seen in the metatarsal heads
b. Direct Extention- is secondary to trauma or surgery, will first effect the
periosteum, then the cortex and finally the marrow. Proteolytic enzymes
destroy Sharpey's fibers
c. Contiguous- is the spread of infection from contiguous soft tissue to the
underlying bone, also will first effect the cortex and finally the marrow
d. Vascular insufficiency

3. Pathophysiology (Small Vessel Osseous Anatomy)

I. From the last stages of intrauterine life up to the first six months, growth
cartilage is established but not yet limited by bone on the epiphyseal side
a. Vessels from the metaphysis penetrate the end of the anlage, perforating
the pre-existing plate
b. At their ends, those vessels expand forming large venous lakes resembling
metaphyseal sinusoids, which are situated close to the surface of the
epiphysis
c. This explains the frequency of infection of the joint and of the epiphyseal
side of the preliminary growth cartilage in the infant
d. Any severe damage to the cells at the epiphyseal side of the growth plate
is irreversible and consequently, joint damage and arrest or disorganized
growth may result in the infant
e. The isolation of the epiphysis from the metaphysis caused by the
epiphyseal plates provides protection both for the epiphysis and the joint.
This explains the rarity of joint infections and epiphysitis in children
II. Physiological factors
a. Intrinsic host defense: Acute hematogenous osteomyelitis (AHO) localizes
in the metaphyseal region because of the phagocytic function in the area of
bone. The normal individual displays abundant phagocytic activity in the
medullary region of bone. AHO occurs in the medullary region of the
diaphysis in sickle cell disease because of inpaired host defense
b. The cortex of the child's bone is thick in the diaphyseal region but thin and
porotic in the metaphyseal region, therefore, an infection
usually spreads laterally through the metaphysis toward and through the thin
porotic cortex.
c. Pus usually spreads through the Haversian system to the subperiosteal
space, with the periosteum being stripped from the cortex: The blood supply
to the cortex is eliminated either by rupturing as the periosteum is elevated
or by bacterial emboli. The periosteum in the child displays 3 differences from
the adult: it is thick, well, vascularized, and loosely attached to the
bone.
d. There are 3 commonly involved metaphyses whose adjacent joints are not
safe from an early infection (child). The following are the joints whose
metaphysis is intra-articular: hip joint, shoulder joint and ankle joint
(distal lateral aspect of the tibial metaphysis is intra-articular).

4. Clinical Presentation and Diagnosis

The clinical presentation is variable and may depend on the age of the
patient, the virulence of the organism, the stage and type of disease process.

NOTE* The tenets of treatment include identification of infecting organism,

selection of appropriate antibiotic and surgical excision of dead bone

a. Symptoms (AHO):
i. Local warmth over the infected area
ii. Pain and tenderness on ambulation and palpation
iii. Pseudoparalysis (often the only complaint in kids) and possible subtle gait
changes
iv. Palpable swelling if the infection has ruptured the cortex into the
periosteum
v. Ulceration or soft tissue lesion(s) may produce contiguous OM
vi. Concurrent infection: Measles/chicken pox may give strep AHO.
Middle ear infections may give hemophilus/pneumococcus/staph

AHO
b. History & Physical: In pediatric AHO recent infections may be implicated as
causative pathogens
c. Laboratory Exams:
i. Same basic studies as with management of inpatient infection
ii. Leukocytosis or a shift left is not commonly seen in acute or chronic OM
iii. Sed Rate is usually increased (a nonspecific exam useful to monitor the
response to treatment)
d. Radiographs:
i. Always take bilateral x-rays for comparative purposes
ii. The lytic process in bone is not visable on x-ray until at least 30%50% of
the osseous mineralization of the area has been lost
iii. The first bone changes occur 10-14 days following the onset of symptom
iv. Baseline radiographs must be taken- (look at the soft tissue first, may find
edema in the contiguous soft tissues, with swelling of one tissue layer as
compared to another)
v. Three stages of soft tissue changes have been discribed in children with
AHO: small deep local. soft tissue in region of metaphysis, swelling of muscles
and obliteration of lucent plane between them and superficial subcutaneous
soft tissue edema which occurs 3 days after onset of symptoms (if aspirate
bone during this phase, should be able to extract pus).
vi. Additional radiographic findings are: periosteal elevation, metaphyseal
destruction (children), regional osteoporosis, sequestrum and involucrum.
vii. Radiographic findings in chronic OM are:
thickened/irregular/sclerotic bone, elevated periosteum, chronic draining
sinus and sequestrum
e. Aspiration (bone/joint biopsy): Confirms the diagnosis, identifies the
organism and aids in determining the treatment plan.
f. Blood Cultures:
i. Are positive in 50% of cases of septic arthritis and osteomyelitis.
ii. The joint fluid in septic arthritis is sterile in 30% of the cases- look at the
blood cultures.
g. Wound cultures:
i. Sinus tract cultures frequently yield gram(-) organisms which are not
responsible for the underlying bone infection.
ii. If Staph aureus is cultured out, there is a 50% chance that this organism is
producing the associated osteomyelitis.
h. Bone cultures:
i. Take specimens for gram stain, aerobic, anaerobic, fungal and acid
fast cultures
ii. Take a specimen for histology

i. Bone Scans:
i. In most patients with osteomyelitis, bone scintograms become positive
within 48-72 hours after onset of clinical symptoms (precedes the x-ray
changes by 10-14 days)
ii. Predominant scintigraphic finding is a "hot spot" (increased tracer
localization)
iii. The exception to this are "cold spots" which is due to NO delivery of the
tracer due to necrosis or a fulminating destructive osteomyelitis not
accompanied -by significant reparative processes
 99m Technetium MDP: is currently the most frequently used radionuclide
It is renally excreted, has a half-life of 6 hours, deposits more in trabecular
than cortical bone and provides more anatomic information with less time,
exposure and expense than Gallium 67 imaging. 99m TC MDP may continue to
show abnormal isotope accumulation after infection subsides as a result of
continued bone repair.
 Three Phase Bone Scan: is used to differentiate OM from cellulitis.
Phase 1- at time of injection shows an immediate radionuclide angiogram or
dynamic blood flow, OM and cellulitis both show increased uptake at this
point.
Phase 2: 5-10 minutes after injection looking for focal increases (blood pool
image) cellulitis and OM are still positive at this point.
Phase 3: 4 hours after injection (delayed static scan), cellulitis becomes
quiescent at this point.
j. Gallium 67: Almost all IV injected Gallium binds to transferrin, with 1/3
excreted by the G.I. tract and 1/3 by the kidneys. More tracer is localized in
the metaphyseal area. Imaging is done 48 hours after tracer administration.
Resolution of anatomical detail for bone lesions is considerably less with
Gallium than with 99m TC MDP, with higher radiation exposure. This scan is
preferred to 99m TC MDP in evaluating the response to treatment and is not
as dependant on blood flow. More specific in differentiating. bone tumors
from osteomyelitis and more reliable in assessing subacute and chronic
infections.
k. Multiple Tracer Studies: When both types of study are needed the bone
scan scan should precede the Gallium scan by 24 hours. The following lists
some scenarios when multiple studies are used:

(+) 99m Tc MDP & - Ga67= chronic osteomyelitis

diabetic osteoarthropathy
implant loosening/ectopic bone (-) 99m Tc MDP & (+) Ga67= cellulitis

(+) 99m Tc MDP & (+) Ga67= acute osteomyelitis

implant loosening

(+) 99m Tc MDP & (+++) Ga67= infection in the presence of an implant

l. 111 Indium White Cell Scanning: This scan is much more specific for
infection. With this scan, white blood cells are labeled with the tracer (Indium)
and injected intravenously. This technique was developed to detect leukocyte
accumulation at sites of inflammation and abscess formation. Scans are
performed 24 hours after injection. A positive scan is defined as a focal
accumulation of leukocytes that is higher than in the surrounding bone. This
technique is reserved for complicated posttraumatic or post-surgical patients
with equivocal conventional bone scans, in cases where 99m TC MOP
scanning reveals false positive results because of rapid turnover. Therefore, it
may be more accurate in detecting acute infections.

NOTE* Limitations of Scans: Some patients show multiple hot spots at an

early stage of S. aureus septicemia but do not progress to OM. You can
have a negative scan with a confirmed OM due to impaired blood supply
(falsenegative). You can have difficulty in differentiating OM from
cellulitis. You can have difficulty in differentiating normal bone repair
from bone infection (falsepositive).
m. Computerized Tomography: An additional technique that can be used to
evaluate OM, especially the articular surfaces and periarticular soft tissues.
Also with OM, elevation of attenuated values in the marrow space is an early
sign of an acute bone infection. The non-specific destruction of cortical bone
and new bone formation can be seen in this way and the progression and/or
recession of disease may be monitored.
n. Magnetic Resonance Imaging: MRI distinguishes soft-tissue structures more
readily than any other imaging modality. It can differentiate osteonecrosis
and aseptic necrosis since most artifacts of bone occur in fatty tissue which is
easily imaged by MRI. Can be used on OM by evaluating the marrow. This is
because water has a high proton content and MRI measures water content of
various body tissues (CT measures specific gravity). The more water the
higher the signal intensity. The following tissues are ranked on the relative
Spin-Echo Grayscale from brightest (short T1 and/or long T2) to darkest
(long T1 and/or short T2 and/or low proton density): fat, marrow, cancellous
bone, brain, spinal cord, viscera, muscle, fluid filled cavities, ligaments,
tendons, blood vessels, compact bone and air. (SEE SECTION ON RADIOLOGY)

5. Acute Hematogenous Osteomyelitis

a. Is a result of blood stream dissemination of bacteria emanating from an
identifiable focus of infection or developing during transient bacteremia
unrelated to a discernable infection
b. Blunt trauma to long bones precedes AHO 33% of the time, femur, tibia
and humerus in that order.
c. Infections usually begin in the metaphysis
d. Large cortical involucrum formation is typical of AHO in the child
e. Three common sites of damage based on age of the patient: epiphyseal
anlage and joint in the infant, cortex of shaft in the child and joint and
marrow in the adult
f. AHO (infants):
i. Causes severe and often permanent epiphyseal damage and joint infection
ii. Only transient damage to shaft and metaphysis
iii. Adjacent joint effusion 60-70% of the time
iv. Group B Strep, S. aureus and E.coli are most frequent organisms
v. Calcaneal AHO reported secondary to repeated venipunctures
g. AHO (child):
i. Extensive cortical damage with involucrum formation
ii. Permanent damage to growth cartilage and to joints is rare iii. Chronic OM
is a rare complication
iv. S. aureus and epidermidis 60-90% cases
v. Salmonella seen with sickle cell (in the diaphyseal area)
vi. H. flu implicated in kids under 2 years
h. AHO (adult):
i. Relatively common in IV drug users with #1 pathogen being Pseudomonas
ii. Usually affects axial skeleton and/or irregularly shaped bones (wrist/ankle)
iii. The cortex is absorbed instead of sequestering
iv. The whole bone is invaded and frequently results in chronic infection of the
whole marrow

6. Contiguous Osteomyelitis:
a. Most common form of OM seen in podiatry.
b. Chronic ulcerations may frequently lead to contiguous OM.
c. May develop when an infection arises in an area adjacent to bone in which
a malignancy is present or bone has received radiotherapy.
d. Staph aureus is the most frequent pathogen.

7. Osteomyeltis associated with peripheral vascular disease:

a. Commonly found in patients with diabetes mellitus or with severe p.v.d.
b. Usually a mixed aerobic and anaerobic infection.

8. Chronic Osteomyelitis:
a. Long standing OM is associated with sequestration.
b. Indolence of the infection is sometimes related to the suppressive effects
of antibiotics in low doses.
c. Staph aureus is the most common pathogen.
d. The phalanges and metatarsal heads are the most common sites. e. The
sed rate is elevated in 57% of these patients. f. Increased warmth over the
infected area found in 94% patients.
g. Pathogens residing in the "dead bone" if not removed along with the
sequestra, can cause acute flare ups as late as 50 years after the initial
episode.

NOTE* Dead bone (sequestrum) acts as a foreign body

The sequestrum must be surgically removed
15-30% of individuals with acute OM or those with chronic OM
who have undergone surgical debridement, develop active flare ups

h. Squamous cell carcinoma has been reported as a late sequel of chronic

OM (foul smelling discharge, increased pain, increased drainage and enlarged
mass), in local draining skin sinuses.

9. Osteomyelitis secondary to puncture wounds:

a. Usually caused by a nail driven into the foot.
b. Suspicion should arise with patients who present with persistent cellulitis
despite soaks and antibiotics and when an I&D produces a foreign body.
c. Pseudomonas is the most common organism.

10. Brodie's Abscess:

a. A small metaphyseal lesion with well defined margins which is often tibial
and which occurs in young males prior to epiphyseal closure.
b. The complaint is recurrent pain, with relief from aspirin, therefore must r/o
osteoid osteoma.
c. S. aureus is the predominant organism.
d. Treated with debridement and curettage and antibiotics e. Can act as site
for local flareups and systemic infections

11. Treatment: Conceptually, It is easy to formulate and describe principles

to follow in planning therapy for a patient with osteomyelitis.
a. The principles that should be considered in the treatment of OM are:
i. A definitive bacterial diagnosis is required
ii. The choice of antibiotics depends on the susceptibility of the etiologic
agent, and the least toxic, least expensive, bacteriocidal antibiotic should be
administered
iii. Surgical intervention must remove devitalized bone that is inaccessible to
antibiotics and may provide a culture medium for continued bacterial growth.

NOTE* Despite the apparent clarity and simplicity of these statements,

diffilculties can arise in their application. This standard set of b.
principles is aimed at providing a clinical and bacteriological cure. A
However, in treating osteomyelitis, one must also consider the best
functional result for the patient. The patient may decide that
intermittent short course antibiotic therapy for control of chronic
osteomyelitis is more acceptible for functional needs than amputation
of the affected limb. It becomes imperative to involve the patient in
these difficult decisions.
debate rages regarding the length of parenteral antibiotic therapy (36
weeks).
c. Surgical debridement generally expedites the resolution of the infection
and can decrease the duration of parenteral antibiotic therapy.
d. The spectrum of pathogens causing OM secondary to a contiguous focus or
PVD is usually broader than found in AHO. The selection of antimicrobials for
contiguous focus OM must be based on C&S from the infected bone.
e. OM secondary to PVD is commonly associated with a mixture of aerobic
and anaerobic organisms. The isolation of anaerobes on C&S, presence of
organisms on a gram's stain that fail to subsequently grow in vitro, and the
existence of a foul odor should guide therapy towards anaerobic bacteria.
Gram positive anaerobes such as Clostridium or peptostreptococci can be
adequately treated with penicillin. However, anaerobic OM usually involves
gram negative organisms such as Bacteroides fragilis which can be treated by
clindamycin or metronidazole. Mixed aerobic/anaerobic infections can be
treated with combined antimicrobial therapy. Third generation cephalosporins
(except Claforan for B. frag) are resistant to 20% of the anaerobes so should
not be used.
f. In a study of oral therapy it was found that S. aureus OM was treated
successfully with 1-2 weeks of IV antibiotics to stem the acute flare up
followed by oral therapy (cloxacillin/dicloxicillin or clindamycin + probenecid)
for as long as 6-12 months (J. Medicine 1976).
g. Treatment for puncture wound OM involves a good history (including a
tetanus history), x-rays, cleanse foot with Betadine, remove any foreign body
making the entrance wound larger if necessary, take deep cultures, flush well
and if gross contamination pack the wound open

NOTE* Oral antibiotic therapy prescribed after the original puncture wound
may contribute to a later OM infection

h. Implantation of gentamycin/ methylmethacrylate beads has been shown to

be helpful as adjunctive therapy for contiguous focus OM.

Septic Arthritis
1. Occurs most commonly in infants and children
2. Adults will generally have an underlying disease
3. Pathogens vary according to the age of the patients with S. aureus
predominating in all age groups
a. H. influenza 2nd most common organism in patients under 2
b. N. gonorrhea 2nd most common organism in adolescents
c. Enterobacter and pseudomonas 2nd most common organisms in patients
older than 50
4. Diagnosis is made via sterile aspiration of pus with a positive gram stain
and C&S.

Radiographic diagnosis reveals loss of subchondral cortical bone with

preservation of underlying supporting trabeculae 5.
Treatment:
a. Serial aspirations vs. surgical decompressions
b. Suction irrigation
c. Parenteral antibiotics
d. Do not use intra-articular injections of antibiotics (can cause a super-
infection or a post-infection synovitis)

Mycology

Fungi are heterotrophic, eukaryotic, chlorophyll-free, thallophytic organisms.

They reproduce by spores, which germinate into long filaments called
hyphae. The hyphae grow and branch and develop into a mat of growth
called the mycelium. Spores are produced from the mycelium. Fungi are
divided into 4 groups
 Phycomycetes
 Blastomycetes
 Ascomycetes
 Fungi Imperfecti (most pathogenic fungi are in this group)
Those fungi affecting humans can be divided into either superficial
(dermatophytes) or deep fungi
Diagnosis is based upon microscopic examination (KOH prep) and culturing
the organism on Sabouraud's medium. Additionally, a Wood's light can be
used for the diagnosis of some organisms, Calcoflour White stain is used
with fluorescent microscopy, India ink smear for detecting cryptococci in the
CSF, Gomori Methamine Silver and Neutral Counter stain for histopathology
slides

1. Superficial Mycoses
a. Tinea Versicolor
b. Candidiasis
c. Onychomycosis
d. Tinea capitis
e. Tinea corporis
f. Tinea pedis
g. Tinea cruris
h. Trichomycosis axillaris

2. Deep Subcutaneous Fungal Infections

a. Sporotrichosis: granulomatous infection of the skin and subcutaneous
tissue, spread via lymph channels, skin lesions present as raised
erythematous plaque-like lesions, a chancre will develop at site of entry and
has rare systemic manifestations (Amphotericin B). Often occurs in those
working with roses, whose thorns inoculate the organisms.

b. Blastomycosis: begins as a papular lesion which ulcerates and spreads

with a pustular border. Treatments include local excision of the early lesion or
the drug 2-Hydroxystilbamidine.

c. Mycetoma: is a chronic granulomatosis infection of the soft tissue and

bone. It requires the triad of an indurated swollen lesion, draining sinus and
unilateral presentation for a clinical diagnosis. It is seen in endemic
proportions in some third world countries. "Sulfur granules' describes material
that exudes from the sinus. It is a form of 'Madura Foot`.

d. Madura foot: may either be fungal (Madurella mycetoma/Pertriellidum

Boydii) or bacterial (Nocardia/Actinomyces/Streptomyces/Achnomadura).
Diagnosis is via gram stain, KOH prep, and testing with Saubouraud's (fungal)
or blood agar (bacterial). Longstanding infections will produce multiple
osteolytic lesions in bone. Treatment involves sulfonamides, local wound
care, and debridement or amputation in severe cases. Infectious disease
specialist should be consulted

NOTE* In addition to the above there are actinomycosis, candidiasis,

chloromycosis,
NOTE* coccidioidomycosis,
Antifungal therapycryptococcosis,
can consist of the
geotrichosis,
following:
histoplasmosis,
1. Imidazole
nocardiosis,
and Triazoles:
aspergillosis,
inhibit
andergosterol
mucormycosis.
synthesis
These
in the fungal cell wall
are more common
2. Imidazoles:
in immunosuppressed
econazoles, ketoconazoles,
patients, e.g.
sulconazoles,
AIDS, terconazole,
uncontrolled
clotrimazole,
Diabetes mellitus,
oxiconazole
malignancies (especially of
hematopoietic
3. Triazoles:
and lymphoid
itraconzole,
tissues)
fluconazole
4. Miscellaneous: allylamine, terbinafine (Lamisil), griseofluvin
Viral Diseases

Viruses are the smallest and most simple biologic units that can manifest the
essential aspects of a living substance. Some important facts about viruses
are:
 They are composed of an outer coat of protein and an inner core of nucleic
acid
 The viruses reproduce heritable characteristics in a predictable manner
during multiplication and demonstrate genetic continuity
 A virus infected cell is immune to reinfection by the virus and also immune
to infection from other viruses usually related to the one which infected it
 The virus infected cell can support the reproduction of the virus which
entered it and may produce new virus particles in a relatively short time
 The most common form of damage in cells supporting viral reproduction is
a cytopathic effect which leads to deterioration and results in death and
disintegration

Viruses are classified according to the target organ and similarity of action.
They are:
1. The pox group (vaccinia and smallpox)
2. Neurotrophic viruses (poliomyelitis, rabies, and arthropod-transmitted
encephalitis including Japanese, St. Louis encephalitis, equine encephalitis
and aseptic meningitis)
3. Viseotrophic viruses (yellow fever, infectious hepatitis and homologous
serum hepatitis)
4. The herpes group
5. Varicella and herpes zoster
6. The myxoviruses (mumps and influenza)
7. The lymphogranuloma psittacosis group
8. Miscellaneous viruses (measles, rubella, Coxsackie viruses, the common
cold, warts, etc.)
9. Bacteriophage

Rickettsial Diseases
Rickettsial diseases are caused by intracellular microorganisms which are
classed between bacteria and viruses, and have characteristics of both. These
pleomorphic, cocco-bacillary organisms can cause acute, febrile, self-limited
symptoms usually accompanied by a skin rash. The group of diseases
includes typhus, Rocky Mountain spotted fever, tsutsugamushi, and Q fever.
Diagnosis is via serologic testing (the Weil-Felix test is useful)

Protozoan and Metazoan Infections

These infections are common in the warmer climate countries. When a
parasite invades a host, there are 4 possibilities:
 The parasite may die at once
 It may survive without causing symptoms
  It may survive and cause disease
 It may kill the host
Protozoa are one-celled organisms and metazoa are invertebrates made up of
many cells (such as worms) replicating directly within a human host

1. Protozoan infections
a. Amoebic dysentery
b. Malaria
c. Trypanosomiasis
d. Leishmaniasis
e. Toxopiasmosis

2. Metazoan infections (parasitic)

a. Nemathelminthes (roundworms)
b. Platyheiminthes (flatworms)
i. Trematoda (flukes)
ii. Cestoda (tapeworms)
c. Hirudinea (leeches)
d. Arthropoda (insects and related species), as in scabies, fleas, tunga
penetrans, maggots (myiasis) etc.

NOTE* Stool examination for the egg larvae and the organisms themselves
are diagnostic for some intestinal protozoa and metazoa. Blood smears
using special staining techniques aid in the diagnosis of some protozoan
infections. Some special stains can detect protozoa in tissue biopsies