A compact guide to differential diagnosis and management of infections and their presentation in malpractice litigation.

1. Naira Renault (former N.Matevosyan) MD, PhD, MSJ
MSJ
INFECTIOUS AGENTS
09.30.2017 Seton Hall University School of Law . Emory University . CDC

2. CLASSIFICATION -Bacteria
COCCI
GRAM-POSITIVE
GRAM-NEGATIVE
22
Staphylococcus: S. aureus, S. epidermidis, S. saprophyticus
Streptococcus: S. agalactiae / β-hemolytic streptococcus, B-strep.
S. viridans / α-hemolytic streptococcus, S. mutans
S. pneumoniae
Neisseria: N. meningitidis, N. gonorrhoeae
Moraxella: M. atlantae, M. catarrhalis, M. osloensis
Kingella: K. kingae
Acinetobacter: A. baumannii, A. calcoaceticus, A. lwoffii,
A. pittii

3. Bacteria (continued)
RODS
GRAM-POSITIVE
- SPORE FORMING
Bacillus (B. anthracis, B. cereus)
Clostridium: (C. botulinum, C. defficile, C. perfrigens, C. tetani)
- NON SPORE FORMING
Corynebacterium diphtheriae, Listeria monocytogenes
GRAM-NEGATIVE
- ENTERIC
Escherichia coli, Klebsiella pneumonia, Shigella, Vibrio (V. cholerae, V.
parahaemolyticus), Yersinia enterolitica, Salmonella (S. typhus, S. cholera-
suis, S. enteritidis), Bacteroides, Campylobacter jejuni, Helicobacter pylori,
Pseudomonas aeruginosa, Burkholderia cepacia, Fasobacterium,
Stenotrophomonas maltophilia
- NONENTERIC
Haemophilus (H. influenzae, H. ducreyi), Gardnerella vaginalis, Brucella,
Bordetella pertussis, Legionella pneumophila, Yersinia pestis, Francisella
tularensis, Pasteurella multocida
33

4. Bacteria (continued)
GRAM-POSITIVE BRANCHING FILAMENTS
PLEOMORPHS
44
Actinomyces: A. bovis, A. dentalis, A. europaeus, A. funkei, A.
georgiae, A. hyovaginalis, A. israelii, A. meyeri,
A. nasicola, A. neuii, A. oricola, A. suis, A.
turicensis, A. vaccimaxillae
Nocardia: N. asteroides, N. brasiliensis
Chlamydia: C. pneumoniae, C. psittaci, C. trachomatis
Rickettsia: R. akari, R. conorii, R. honei, R. rickettsii,
R. prowezekii, R. typhi
Bartonella: B. bacilliformis, B. henselae, B. quintana,
R. rochalimae
Coxiella burnetti Ehrlichia chaffeensis

5. Bacteria (concluding)
GRAM NEGATIVE SPIRALS:
Treponema pallidum: T. carateum, T. endemicum (Bejel)
Borrelia burgdorferi (Lyme disease)
Leptospira interrogans (Weil disease)
GRAM-POSITIVE ACID-FAST:
Mycobacterium tuberculosis (TB)
Mycobacterium leprae (lepromatous leprosy, tuperculoid leprosy)
GRAM-POSITIVE WITH NO CELL WALL:
Mycoplasma: M. genitalium, M. haemophelis, M. hyorhinis,
M. mycoides, M. pneumoniae, M. synoviae
Ureaplasma: U. parvum, U. urealyticum
55

6. Basic facts about the bacteria
All bacteria have a peptidoglycan cell wall which is thick in Gram-
positives and thin in Gram-negatives.
In addition, Gram-negatives have a lipopolysaccharide (LPS)
layer coating the cell-wall from outside, which prevents the Gram
nuclear-stain purple dye (safranin) coloring the cell-wall. In the
result, Gram-positive bacteria retain purple or blue color, while
the Gram-negatives do not – remaining pink.
The LPS layer in Gram-negative bacteria contains an endotoxin
(lipid-A) that activates cytokine-mediated immune response in a
host, resultant in septic shock.
Gram-positive bacteria do not have such an attack-mechanism
(i.e. lipid-A). Instead, all Gram-positives (except Listeria) have
exotoxins of three kind: pyrogenic (lipid-M), tissue invasive, and
miscellaneous.
66

7. More about the bacteria
AEROBISM: Based on the agent's ability to synthesize its own adenosine
triphosphate (ATP), the bacteria are stratified to present:
77
Obligate aerobes
require oxygen to survive
(cellular respiration)
Mycobacterium tuberculosis,
Nocardia asteroides,
Pseudomonas
Facultative aerobes
prefer oxygen but can survive
without it via fermentation
Staphylococci, Streptococci, E-coli,
Listeria, Shewanella oneidensis
Obligate anaerobes
can't live with the presence of
oxygen
Actinomyces, Bacteroides,
Clostridium, Chlamydia, Rickettsia,
Fusobacterium, Porphyromonas,
Peptostreptococcus, Prevotella,
Propionibacterium, Veillonella
Obligate intracellular
organisms
can't make their own ATP, and
rely on the host cell
machinery for survival
Bartonella henselae, Brucella,
Francisella tularensis,
Salmonella typhi
Facultative
intracellular
organisms
don't need to live in cells but
can survive and replicate in
macrophages after being
phagocytosed, because of the
enzyme protection against
superoxide radical digestion.
Histoplasma capsulatum,
Legionella, Shigella

8. More about the bacteria
INVASIVE MEANS & STRUCTURES: Flagella, Capsules, Spores, Biofilms,
Enzymes (transpeptidase, C5a peptidase, penicillin-binding protein [PBP], catalase,
coagulase, hyaluronidase, streptokynase, superoxid dismutase, streptolysin O, S), Toxins:
endotoxin (lipid-A, nitric oxide) in Gram -negative and exotoxins (lipid-M, exotoxin-B,
erythrogenic toxins) in Gram + (except Listeria).
SHAPES: Cocci (spheres), Bacilli (rods), Coccobacilli (short rods), Spirals (comma,
S, and spiral-shaped), Pleomorphic (no distinct shape) (Slides 2-6).
CATALASE: All staphylococci produce catalase, whereas streptococci do not.
Catalase is an enzyme that degrades H2
O2
before it can be converted to microbicidal
products by the enzyme myeloperoxidase.
SOME MNEMONICS:
88
J.O.N.E.S. Evidence of the prior
streptococcal infection
Joints (polyarthritis), Obvious (peri, myo,
endo-carditis), Nodules, Erythema
(marginal rash), Sydenham chorea
H.A.C.E.K.
Bacteria that cause
culture-negative
endocarditis
Haemophilus, Actinobacillus,
Cardiobacterium, Eikenella, Kingella
B.E. P.S.E.U.D.O. Opportunistic
pseudomonas in the
immune-suppressed
patients
Burns (leading to sepsis), Endocarditis
(from IV infusions), Pneumonia (in cystic
fibrosis), Sepsis, External otitis (in elderly,
or diabetes), UTI (from Foly catheter),
Diabetic Osteomyelitis (foot ulcers, IV)

9. CLASSIFICATION -Viruses (DNA viruses)
(HHAPPPy) - icosahedral capsid (except Pox's complex capsid); either enveloped or
naked; DNA strands vary (double -ds, single -ss)
99
H Hepadnoviridae: Orthohepadnovirus (Hepatitis B)
enveloped,
circular dsDNA
H Herpesviridae:
HHV-1,2 (Herpes Simplex V., HSV-1, HSV-2)
HHV-3 (Varicella Zoster Virus, VZV)
HHV-4 (Epstein-Barr Virus, EBV)
HHV-5 (Cytomegalovirus, CMV)
HHV-6 (Roselovirus, RLV)
HHV-8 (Kaposi Sarcoma)
enveloped,
linear dsDNA
A Adenoviridae:
50 sub-types:
A,B,C,D,E,F,G (pharyngoconjunctival fever)
1, 2, 3, 5, 19, 21 (pertussis like illness)
11 (acute hemorrhagic cystitis), etc
naked, linear
dsDNA
P Parvoviridae Parvovirus B 19 naked, linear
ssDNA
P Poxviridae . Variolla Virus
. Molluscum Contagiosum
naked, circular
dsDNA
Pyy Papovaviridae
. Human Papillomavirus (HPV)
Strains 6, 11 (benign warts - genital, nongenital)
Strains 16, 18 (cancer – cervical, anal, oropharynx)
. Polyomavirus (BK - urogenital, JC -CNS)
naked, circular
dsDNA

10. NAKED VIRUSES: all have icosahedral capsid; positive sense; single-stranded
RNA (Picornoviruses, Hepevirus, Calicivirus), double-stranded segmented RNA
(Reoviruses)
1010
CLASSIFICATION -Viruses (RNA viruses)
Picornaviruses: P.E.R.C.H.
Poliovirus, Echovirus, Rhinovirus,
Coxsakievirus, Hepatitis - A virus
ssRNA,
linear
Hepevirus: Hepatitis - E
ssRNA,
linear
Calicivirus: Norwalk virus (norovirus)
ssRNA,
linear
Reoviruses: R. E. O.
Respiratory, Enteric, Orphan
Ex: Rotavirus, Colorado tick fever
dsRNA,
segmented

11. RNA viruses (continued)
ENVELOPED VIRUSES:
Structural diversity
1111
Single-stranded RNA: All enveloped RNA viruses
Double-stranded RNA: None
Linear RNA:
Coronavirus, Filovirus, Flavivirus, Orthomyxovirus,
Retrovirus, Paramyxovirus, Rhabdovirus, Togavirus
Segmented RNA: Bunyavirus
Circular RNA: Arenavirus, Deltavirus
Icosahedral capsid: Flavoviruses, Retroviruses, Tagaviruses
Helical capsid:
Arenavirus, Bunyavirus, Coronavirus, Deltavirus,
Filovirus, Orthomyxovirus, Paramyxovirus,
Positive sense: Coronavirus, Flavivirus, Retrovirus, Togavirus
Negative sense:
Arenavirus, Bunyavirus, Deltavirus, Filovirus,
Orthomyxovirus, Paramyxovirus, Rhabdovirus

12. RNA viruses (concluding)
1212
Flaviviruses: Hepatitis -C, West Nile virus, Dengue fever (yellow fever)
St. Louis encephalitis, Japanese encephalitis, Zika virus (ZIKV)
Togaviruses: Alpha virus (Easter and Western equine encephalites),
Rubivirus (Rubella)
Retroviruses: Human T-lymphotrophic virus (HTLV)
Human immunodeficiency virus (HIV)
Coronaviruses: Severe acute respiratory syndrome (SARS)
Orthomyxovirus: Influenza virus (flu)
Paramyxovirus: Parainfluenza virus (stridor), Respiratory syncytial virus (RSV),
Mumps (parotidis), Rubeola (measles)
Rhabdovirus: Rhabies
Filovirus: Marburg virus (hemorrhagic fever), Ebola virus
Deltavirus: Hepatitis-D virus (HDV)
Arenavirus: Lymphocytic choriomeningitis virus (LCMV)
Bunyaviruses: Crimean-Congo hemorrhagic fever virus, California
encephalitic virus (CEV), Hantavirus, Rift Valley virus

13. Basic facts about the viruses
All viruses are haploid (one copy of either DNA or RNA), except Retrovirus which has two
identical ssRNA strands.
The viral core (nucleic acid, DNA or RNA) is covered by a protective protein coat (capsid).
Together they form nucleocapsid.
Viruses are classified by the (1) nucleic acid (RNA, DNA), (2) shape of the capsid (helical,
icosahedral), (3) presence/absence of an outer coat (envelope) that distinguishes naked
(aggressive) viruses from the enveloped (vulnerable) ones.
Icosahedral virus capsids are assigned a triangulation number (T) to describe the relation
between the number of pentagons and hexagons, the quasi-symmetry in capsid shell. A
purely dodecahedral virus has T=1; a truncated icosahedron is assigned T=3. T is
calculated by applying a grid to the viral surface with coordinates h and k and counting
steps between successive pentagons on the surface as shown in the formula:
T = h2
+ h x k + k2
= (h + k)2
– hk
where h and K ( h > k) are distances between the successive pentagons on the viral
surface for each axis.
Viral classification uses ICTV system: orders (virales), families (viridae), subfamilies
(virinae), genera (virus), species (virus).
All DNA viruses are double-stranded (dsDNA) except for Parvovirus (ssDNA).
All RNA viruses are single-stranded (ssRNA) except for Reoviruses (dsRNA).
The DNA viruses are remembered by the HHAPPPy mnemonics (Slide 9).
Picornaviruses (naked, RNA) are remembered by the PERCH mnemonics (Slide 10).
All DNA viruses have linear genomes except for Papillovirus, Polyomavirus, Hepadnavirus
(that have circular genomes). 1313

14. More about the viruses
All DNA viruses replicate in the nucleus and are icosahedral,
except for Poxviruses that replicate in cytoplasm and have
complex capsids.
All RNA viruses replicate in the cytoplasm except for
Retroviruses and Orthomyxovirus (influenza v.) that replicate in
the nucleus.
All viruses need viral polymerase or reverse transcriptase in
order to be blended to the host cell's transcription/translation
machinery. So, the naked-genomes are invasive in the:
(A) (+) single-strand RNA viruses because their genome is
mRNA which can readily undergo translation, and
(B) linear double-strand DNA viruses because their genome
can be incorporated into the host cell's DNA by double-
stranded break repair mechanism.
1414

15. CLASSIFICATION -Fungi
MAIN GROUPS DISEASES AGENTS
Epidermal infections
Tinea versicolor (spaghetti & meatballs)
Tinea nigra
Malassezia furfur
Exophiala werneckii
Cutaneous infections
Oral thrush
Esophagytis, Vulvovaginitis
Tinea barbae (folliculitis)
Tinea capitis
Tinea corporis (ringworm)
Tinea cruris (jock itch)
Tinea pedis (athlete's foot)
Tinea unguium (onychomycosis)
Candida albans
Piedraia and Candida
Trychophyton
Microsporum
Trychosporon
Epidermophyton
Microsporum
Epidermophyton
Subcutaneous infections
Chromoblastomycosis
Mycetoma (Madura foot)
Sporotrichosis (rose thorn bite)
Cladosporium carrionii
Fonsecaea pedrosoi
Sporothrix schenckii
Systemic mucoses
Blastomycosis (Mississippi fever)
Histoplasmosis (Spelunker's lung)
Coccidiomycosis (Valley fever)
Paracoccidiomycosis (Captain wheel)
Blastomyces dermatidis
Histoplasma capsulatum
Coccidioides
Paracocci brasiliensis
Systemic mucoses in
immunocompromised
individuals
Aspergillosis
Cryptococcus neoformans
Pneumocystis jiroveci
Aspergillus
Cryptococcus meningitis
Pneumocystis carinii
1515

16. Basic facts about the fungi
All fungi infecting humans are eukaryotic, aeorobic organisms.
All fungi have polysaccharide cell wall composed of chitin,
mannans, and glucans.
The cell membrane of each fungus contains ergosterol.
The main mechanism of the anti-fungal treatment (amphotericin-
B, ketoconazole, nystatin) is in targeting ergosterol.
Fungi reproduce both sexually (mitosis) and asexually (budding).
Fungi exist in two forms: unicellular (yeast), multicellular (mold).
Fungi that switch between yeast and mold are dimorphic. These
are mold forms that can morph to yeast at higher temperatures.
The most prevalent systemic mycoses in the Unites States are:
Coccydiomycosis - endemic to California (“San Joaquin Valley
fever”) and Southwest; Histoplasmosis- endemic to Ohio River
Valley and Michigan's Great Lakes region; Paracoccydiomycosis –
endemic to Central and South Americas.1616

17. Fungi structure (continued)
In vegetative phase, fungal cells divide either by mitosis or
budding. Incomplete budding results in pseudohyphae.
True hyphae is when the fungal cells have septa in between.
In reproductive phase, fungal cells produce spores (conidia).
Conidia enclosed within a sporangium sac are endospores.
1717

18. Basic diagnostic skills in fungi
(1) a 43-year old HIV+ male presents with a 2-day history of fever, chills, cough, CD4 count
of 50, oxygen saturation within normal limits, chest X-ray showing right-sided lobar
consolidation; (2) a 43-year old HIV+ male presents with a 5-day history of worsening
fever, chills, productive cough, CD4 count of 50, needing oxygen via nasal cannula, X-ray
showing diffuse bilateral interstitial infiltrates. Diagnoses: (1) community-acquired
Streptococcal Pneumonia; (2) pneumocystic pneumonia caused by Pneumocystis jirovecii
(fungus). Other expected findings may include high LDH, ground-glass opacities on CT
scan, yeast forms (“flying-saucer” shaped) in the sputum.
What distinguishes fungal cell membranes from animal cell membranes? Fungal cell
membranes are composed of ergosterol – unique to fungi. This sterol is the target of many
anti-fungal drugs, including ketaconazole, nystatin, or amphotericin-B.
A 25-year old HIV+ female develops white sores/exudate on the tongue, hard to scrape off.
She after develops pain with swallowing. Diagnosis: Oral thrush caused by Candida. The
later condition is fungal esophagitis, to be differentiated from CMV or HSV esophagitis.
A 30-year old HIV+ man presents with a one-week history of fever and chills, with
progressive headache and neck stiffness. CD4 count is 75. CSF exam reveals encapsulated
yeast with Indian ink stain. Diagnosis: Cryptococcus meningitis.
A 42-year old landscaper pricks her fingers while pruning rosebushes. A week later, a
mildly painful papule develops on her affected finger. Several more ulcerative lesions
appear on her forearm days later. Diagnosis: Sporotrichosis caused by Sporothrix schenckii.
Ascending lymphangitis.1818

19. CLASSIFICATION -Parasites
These are eukaryotic organisms that require a host for the survival. Human parasites
come in two forms: (1) Single-cell protozoa, (2) multicellular helminths.
1919
TROPISM PROZOA / VECTOR DISEASES
CNS infections . Acanthamoeba
. Naegleria fowleri
. Toxoplasma gondii
. Chronic meningoencephalitis
. Acute meningoencephalitis
. Progressive mental state,
congenital T. trio (chorioretinitis,
hydrocephalus, brain calcifications)
Gastrointestinal
infections
. Cryptosporidium parvum
(fecal-oral)
. Entamoeba hystolytica
. Giardia lamblia
. Diarrhea, acid-fast cysts in stool
. Bloody-diarrhea with “anchovy-
paste” stool
. Chronic watery diarrhea, foul-odor
fatty diarrhea, IgA deficiency
Blood-borne
infections
. Babesia microti (Ixodes tick)
. Leishmania (sandfly bite)
. Plasmodium (Anopheles mosq)
. Trypanosoma (tsetse fly bite)
. Treponema Cruzi (reduviid bug)
.Hemolytic anemia
. Leishmaniasis
. Malaria
. Lymphadenopathy, sleeping sickness
. Chagas Disease, Romaňa sign,
lymphadenopathy, cardiomyopathy,
mega-esophagus, megacolon
STDs Trichomonas vaginalis Vaginitis, thin malodorous discharge,
“strawberry cervix”

20. HELMINTHS (continued)
GROUP WORMS / VECTOR DISEASES
NEMATODESNEMATODES
Hookworms (Ancylostoma
dudonale, Necator americanus)
Threadworm (Strongyloides
stercoralis)
Roundworm (Ascaris lumbricoides)
Dog roundworm (Toxocara canis)
Whipworm (Trichuris trichiura)
Pinworm (Enterobius vermicularis)
. Pneumonia, iron-deficiency
anemia, Loeffler syndrome
. Pneumonia, enterocolitis
diarrhea
. Pneumonia, bowel obstruction,
malnutrition
. Hepatitis, myocarditis, seizures,
conjuctivitis, retinitis
. Bloody diarrhea, rectal prolapse
. Nocturnal anal pruritis
Guinea worm (Dracunculus
medinensis, contaminated water)
Loa Loa (horse fly bite)
Onchocerca volvulus (female
blackfly bite)
Trichinella spiralis (undercooked, or
raw pork meat)
Wuchereria bancrofti (female
mosquito bite)
. Subcutaneous larvae
reproduction, pain, GWD
. Callabar swellings, conjuctivitis
. Skin lichenification, “river
blindness”
. Muscle larvae reproduction,
muscle pain, periorbital edema
. Lymphedema, elephantiasis
2020

21. HELMINTHS (concluding)
2121
GROUP WORMS/ VECTOR DISEASES
PLATY-PLATY-
HELMINTHSHELMINTHS
CESTODES (tapeworms):
Taenia (T. saginata, T. solium,
from infected beaf)
Diphyllobotrium latum (fish
tapeworm, from raw fish)
Echinococcus granulosus (dog
tapeworm)
. intestinal obstruction,
abdominal pain, cysticercosis,
neurocysticercosis, seizures
. vitamin B-12 deficiency,
macrocytic anemia
. hydatid cysts in liver,
anaphylaxis, portal abscess
TREMATODESTREMATODES
(FLUKES)(FLUKES)
Clonorchis sinensis (Chinese liver
fluke, from raw/undercooked fish,
duck)
Paragonimus westermani (lung
fluke, from raw/undercooked crab)
Schistosomiasis (blood flukes, from
snails, contaminated water)
. Biliary obstruction, gallstones,
cholangiocarcinoma
. pulmonary inflammation and
cysts, hemoptysis
. “swimmer itch,” Katayama
fever, dysuria, hematuria,
squamous cell carcinoma of
the bladder, liver and spleen
fibrosis, hepatosplenomegaly,
portal hypertension

22. Basic diagnostic skills in parasites
The purpose of thick v. thin peripheral blood smears in Malaria diagnostics is that
the former screens for the presence of Plasmodia, and the later identifies a
specific Plasmodium (P. berghei, P. falciparum, P. knowlesi, P. malariae, P. orale, P.
vivax).
The approximate fever-periodicity in P. vivax (48 hours, tertian fever), P. ovale (72
h, tertian fever), P. malarie (72 h, quartian fever), P. falciparum (irregular
intervals). Long intervals or irregularity are associated with the hypnozoite stage
in the liver.
A 20-year old male presents with a week history of sore throat, fever, and
maculopapular rash over his palms and soles. He reports having multiple sex
partners within the past 3 months and no drug allergies. You administer a dose of
IM penicillin. By leaving your office, he develops erythematous blanching rash
associated with headache, muscle pain, and chills. Diagnosis: This isn't an allergic
reaction, rather it's a Jarisch-Herxheimer reaction caused by simultaneously
accelerated rupture of mass Treponema within the blood stream resultant in
inflammatory cytokine buildup.
A 3-year old girl is brought to the clinic for an itchy rash over her low extremities,
after she was playing in the playground sand barefoot. On physical exam, she has
intensely pruritic, erythematous, serpinginous lesions between her toes and the
dorsal feet. Diagnosis: Cutaneous larva migrans (“creeping eruption”) from
hookworm infection, accompanied by the elevated IgE and peripheral
eosinophilia (Loeffler syndrome).2222

23. Antimicrobials
β - LACTAM ANTIBOTICS
PENICILLIN
FAMILY
MECHANISM COVERAGE RESISTANCE TOXICITY
Penicillins
- Penicillin G
- Penicillin V
Bind PBPs;
inhibit trans-
peptidase cross
—linking of cell
wall; activate
autolytic
enzymes
Gram+ cocci
including
S. pneumoniae,
group A-strep
such as S.
pyogenes,
Actinomyces
Due to
penicillinase (β-
lactamase),
altered porins
(Gram- only)
altered PBPs
Hemolytic
anemia, cross-
reactivity with
cephalosporins
hapten-proteins,
& carbapenems
(for their β-
lactam ring
structures)
Amino-
penicillins
- Ampicillin
- Amoxacillin
Same as above Same as above,
plus Gram- rods
(H. influenzae, E.
coli, Listeria,
Proteus,
Salmonella)
Same as above Rash (especially
in patients w/
mononucleousis),
pseudo-
membranous
colitis
2323 Pencillin family continued

24. 2424
PENICILLIN
FAMILY
MECHANISM COVERAGE RESISTANCE TOXICITY
Penicillin-
Resitant
Penicillins
- Methicillin
- Nafcillin
- Oxacillin
- Cloxacillin
Same as
described in
prior slide
Same as
described before,
plus targeting
methicillin-
sensitive
Staphylococcus
aureus (MSSA).
Altered porins
(Gram- only),
altered PBPs
(MRSA)
Hypersensitivity,
interstitial
nephritis (from
methicillin)
Antipseudo-
monal
Penicillins
- Ticarcillin
- Piperacillin
- Carbenicillin
Same as above Same as above,
plus targeting
Pseudomonas
aeruginosa,
Gram- rods, and
anaerobs such as
Bacteroides
fragilis
Penicillinase (β-
lactamase),
altered porins
(Gram- only),
altered PBPs
Hypersensitivity
reaction
PENICILLIN FAMILY (continued)

25. β - LACTAM ANTIBOTICS (continued)
2525
CEPHALO-
SPORINS
MECHANISM COVERAGE RESISTANCE TOXICITY
1st
Generation
- Cephapirin
- Cephalexin
- Cephazolin
2nd
Generation
Cefaclor
Cefoxitin
Cefatoran
Cefdinir
3rd
Generation
Cefriaxone
Cefixime
Ceftibuten
4th
Generation
Cefepime
Inhibit cell wall
synthesis
similar to
Penicillin; β-
lactam ring is
resistant to
Penicillinases
Gram+ cocci
Proteus mirabilis
Excharichia coli
Klebsiella
pneumoniae.
Note: Gram+
coverage
diminishes and
Gram- coverage
improves with
each new
generation
Cephalospori-
nases, altered
porins (Gram-
only) altered
PBPs
Hypersenstivity
reaction,
increases
nephrotoxicity of
aminoglycosides,
vitamin-K
deficiency,
disulfiram-like
reaction (as with
cases of
mentronidazole,
cefamandole,
cefmetazole,
cefotetan,
cefoperazone,
griseofulvin)

26. β - LACTAM ANTIBOTICS (concluding)
MONO-
BACTAMS
MECHANISM COVERAGE RESISTANCE TOXICITY
- Aztreonam
Inhibit cell wall
synthesis by
binding to PBP3
Gram-negative
aerobic bacteria
only
Does not bind
PBPs of
anaerobes or
Gram+ bacteria
GI upset, no
cross-senstivity
with penicillins or
cephalosporins
CARBA-
PENEMS
- Imipenem
- Cilastatin
- Meropenem
- Ertapenem
- Doripenem
Inhibit cell wall
synthesis similar
to penicillin,
highly resistant
to β-lactamase
Broad Gram+,
Gram-, and
anaerobic
coverage, do not
cover MRSA.
Ertapenem does
not cover
Pseudomonas
aeriginosa
Carbapenemases
(metallo-β-
lactamases such
as NDM-1)
GI upset from
fast IV infusion,
skin rash, CNS
clinics (seizures),
hypersensitivity
reaction.
2626

27. 2727
ANTIRIBOSOMAL ANTIBOTICS
AMINO-
GLYCOSIDES
MECHANISM COVERAGE RESISTANCE TOXICITY
- Gentamicin
- Amikacin
- Streptomycin
- Neomycin
- Tobramycin
Irreversibly bind
to 30S subunit to
inhibit formation
of initiation
complex. Cause
errors of RNA
reading and
translocation
with premature
termination.
Require oxygen
to uptake on
bacteria.
Gram- aerobic
bacteria. No
effect on
anaerobs
because uptake is
via O2 dependent
mechanism.
Tobramyscin is
used in cystic
fibrosis because
of its effect on
Pseudomonas
aeruginosa.
Ribosomal
binding
alteration,
aminoglyside
inactivating
enzymes by
acetylation,
phosphorylation,
and adenylation.
Nephrotoxicity,
ototoxicity,
neuromuscular
blockade,
teratogen.
TETRACYCLINS
- Tetracycline
- Doxycycline
- Minocycline
- Democycline
Reversibly bind to
30S subunit to
prevent
aminoacyl-tRNA
binding with
ribosome-RNA
complex, thus
inhibiting protein
residue
elongation.
Intracellular
pathogens
(Rickettsia,
Chlamydia),
spirochetes
(Borrelia,
leptospira,
Treponema),
Nocardia,
Mycoplasma,
Brucella, etc.
Drug efflux
pumps,
tetracycline
inactivating
enzymes via
acetylation.
GI upset, teeth
decoloration,
phototoxic
dermatitis,
Fanconi
syndrome,
inhibition of
bone growth in
kids, teratogen.

28. 2828
ANTIRIBOSOMAL ANTIBOTICS (continued)
MACROLIDES MECHANISM COVERAGE RESISTANCE TOXICITY
- Erythromyin
- Azithromyicn
- Clarithromycin
Reversibly bind to
23S rRNA of 50S
subunit to block
translocation.
Undergo enter-
hepatic
circulation.
Potent inhibitors
of CYP450
systems, causing
many drug-drug
interactions.
Atypical
pathogens
(Legionella,
Mycoplasma,
Chlamydia), some
Gram+ cocci
(Streptococcus)
Methylation of
23S rRNA
binding site,
macrolide-
inactivating
enzymes via
esterification,
drug efflux
pumps
GI upset,
QT interval
prolongation on
ECG, acute
jaundice and
hepatitis, skin
rash, motilin
agonism,
eosinophilia,
hypocoagulation
through CYP450
blockage
AMPHENICOLS
Chloramphenicol
Irreversibly bind
to 50S subunit to
inhibit peptidyl-
transferase; are
lipid soluble and
easy penetrate to
the CNS
Broad spectrum,
Gram+ , Gram -,
and anaerobs,
Rickettsia, good
choice for
treatment of the
bacterial
meningitis
Reduced
membrane
permeability,
ribosomal
binding site
alteration
Dose-dependent
bone-marrow
suppression,
anemia,
pancytopenia,
doe-
independent
aplastic anemia,
“gray baby”
syndrome.

29. 2929
ANTIRIBOSOMAL ANTIBOTICS (concluding)
LINCOSAMIDES MECHANISM COVERAGE RESISTANCE TOXICITY
- Clyndamicin Irreversibly bind
to 50S subunit,
block peptide
bond formation,
and inhibit
protein synthesis
Anaerobes
(Bacteroides,
Clostridium),
some Gram+
aerobes (Strepto-
Staphylococci,
MRSA), infections
“above the
diaphragm”
Methylation of
23S rRNA
ribosomal
structural
alteration,
intrinsic
resistance to
Gram-negatives
Pseudo-
membranous
colitis, diarrhea,
rash
OXAZOLIDINONES
- Linezolid
Irreversibly bind
to 50S subunit to
prevent
formation of the
initiation complex
Gram+ bacteria
including
methicillin and
vancomyicin-
resistant
organisms; no
affect on Gram-
Point mutation
in 23S rRNA,
resistance to
drug efflux
pumps (Gram-
only)
Bone marrow
suppression,
thrombocyto-
penia, GI upset,
headache,
serotonin
syndrome, MAO
inhibition, SSRI
STREPTOGRAMINS
- Quinupristin
- Dalfopristin
Irreversibly bind
to 23S rRNA of
50S subunit to
inhibit peptidyl-
transferase
Gram + (including
A-strep,
Staphylococci -
including MRSA),
Enterococci
(including VRE)
Streptogramin
inactivating
enzymes by
acetylation, drug
efflux pumps
GI upset, myalgia,
althralgia, rash,
hyperbilirubin-
emia, thrombo-
phlebitis.

30. 3030
MISCELLANEOUS ANTIBOTICS
GLYCOPEPTIDES MECHANISM COVERAGE RESISTANCE TOXICITY
- Vancomycin Inhibit cell wall
synthesis by
blocking trans-
peptidation of D-
alanine
Gram+ bacteria,
including MRSA
Terminal
mucopeptide
amino acid
alteration to D-
lactate or D-
serine, outer
membrance
impermeable to
Gram-
“Red man
syndrome”
(histamine flow),
reversible hearing
loss, nephro-
toxicity; V. is not
absorbed by GI
tract (large
molecule)
LIPOPEPTIDES
- Daptomycin
Inhibits bacterial
DNA, RNA, and
protein synthesis
by depolarizing
the membrane
potential
Gram + (including
methicillin and
vancomycin-
resistant
microbes); does
not treat
pneumonia
Unknown so far Rash,
constipation, GI
upset, insomnia,
rhabdomyolisis
ANTIMETABOLITES
- Trimethoprim
- Sulfamethoxazole
- Dapsone
- Sulfoxone
- Sulfadiazine
Inhibit
dehydrofolate
(DHF) synthesis
and conversion to
tetra-hydrofolate
(THF)
Wide range,
Gram+ and
Gram-
Mutations in the
enzymes that
antimetabolites
bind to
Megaloblastic
anemia (folate
deficiency),
leukopenia,
hemolysis,
nephritis, rash

31. 3131
MISCELLANEOUS ANTIBOTICS (continued)
QUINOLONES MECHANISM COVERAGE RESISTANCE TOXICITY
- Ciprofloxacin
- Levofloxacin
- Moxifloxacin
Inhibit DNA
gyrase causing
DNA double-
strand breaks
Coverage
expands with
generation
Mutations in
topoisomerase II
or IV, drug efflux
pumps
GI upset,
tendonitis,
cramps, myalgia,
tremor, insomnia,
hepatotoxicity
NITROFURANS
- Metronidazole
- Nitrofurantoin
Form nitroso
intermediates in
the cells to
deactivate
numerous
enzymes
Nitro (E.coli, S.
saprophyticus),
Metro (Giardia,
Entamoeba,
Gardnerella, H.
pylori, C. difficile)
Multistep
reduction in
pathways
responsible for
cellular uptake
of drug
Upset with
alcohol use,
metallic taste,
thrombophle-
bitis with IV
form
POLYMYXINS
- Polymyxin-B
- Polymyxin-E
- Colistin
Bind to lipopoly-
saccharide (LPS)
to cause
detergent-like
membrane
disruption
Gram-negative
bacteria only
Modifications of
LPS-binding site
Neurotoxicity,
acute tubular
necrosis
MONOXYCAR-
BOLIC ACIDS
- Mupirocin
Reversibly bind to
isoleucyl – tRNA
synthetase,
blocking ligase
activity & protein
synthesis
Gram+ skin flora
(including MRSA)
Modification of
isoleucyl-tRNA
synthetase site,
acquisition of
mup-A isoleucine
synthetase gene
Rash, pain at
topical
application site

32. BACTERIOSTATIC & BACTERIOCIDAL ANTIBIOTICS
BACTERIOSTATIC BACTERIOCIDAL
Chloramphenicol
Clindamycin
Macrolides
Spectinomycin
Sulfonamides
Tetracyclines
Trimethoprim
Amynoglycosides
Carbopenems
Cephalosporines
Daptomycin
Fluoroquinplones
Metronidazole
Monobactams
Penicillins
Sulfamethoxazole
Vancomycin
3232

33. 3333
ANTIMYCOBACTERIAL MEANS
IZONIAZID MECHANISM COVERAGE RESISTANCE TOXICITY
- Izoniazid Inhibits mycolitic
acid synthesis,
requires bacterial
catalase-
peroxidase to
convert INH to
active metabolite
Intracellular and
extracellular
Mycobacterium
tuberculosis
Loss and
alteration of
bacterial
catalase-
peroxidase,
overexpression in
mycolic acid
pathways
Neurotoxicity,
hepatotoxicity,
drug-induced
lupus,
sideroblastic
anemia, pellagra
RIFAMYCINS
- Rifampin
- Rifabutin
- Rifaximin
Inhibit DNA-
dependent RNA
polymerase; act
as the potential
inducers of
CYP450 system
M. tuberculosis
and atypical
mycobacteria,
wide Gram+ and
Gram- coverage,
including MRSA
Resistant to M.
avium; structural
modification of
RNA polymerase
Red-orange
colorization of
urine, sweat,
tears; jaundice,
hepatitis
PYRAZINAMIDE
- Pyrazinamide
Inhibits fatty acid
synthase I (FASI)
of mycobacteria
M. tuberculosis
& M. africanum
only
Mutations in
gene encoding
pyrazinamidase
Hepatotoxicity,
hyperuricemia
ETHAMBUTOL
- Ethambutol
Inhibits
arabinosyl
transferase to
block carbo-
polymerization of
the cell wall
M. tuberculosis
and atypical
mycobacteria,
Variable
resistance to
MAC, random
spontaneous
genetic
mutations
Optic
neuropathy
(central scotoma,
red-green color
blindness).

34. 3434
ANTIVIRAL AGENTS
Amantadine,
Rimantadine
MECHANISM COVERAGE RESISTANCE TOXICITY
Target M2 protein
ion channel and
block viral
penetration and
uncoating
Influenza-A
only
Resistance to
Influenza-B
strains (used as
alternative
drugs in
Parkinsonism)
Ataxia, dizziness,
slurred speech (less
CNS affects with
Rimantadine which
does not cross HE
barrier)
Zanamivir,
Oseltamivir
Inhibit viral
neuraminidase
and decrease the
progeny virus
count
Influenza A & B Alteration of
neuraminidase
Bronchospasm
during the drug
inhalation
Ribavirin Inhibits inosine
monophosphate
(IMP) dehydro-
genase to
decrease guanine
nucleotides in
replication
Severe
neonatal RSV,
HSV
Effective if
combined with
pegylated
interferon-α
Hemolytic anemia,
teratogenic

35. 3535
ANTIVIRAL AGENTS (continued)
Interferons
(IFN – α, β, γ)
MECHANISM COVERAGE RESISTANCE TOXICITY
Citokine activity
blocks replication
and enhances
clearance of RNA
and DNA viruses
via antiviral gene
transcription
activation
IFN – α (chronic
HCV and HBV,
Kaposi sarcoma),
IFN-β (acute
flares in multiple
sclerosis), IFN -γ
(NADPH oxidase
deficiency in
granulomatosis)
Double-strand
RNA activated
protein kinase
(PRK) in
Hepatitis-C
Neutropenia, flu-
like symptoms,
depression
Acyclovir,
Valacyclovir,
Famciclovir,
Ganciclovir
Creating
triphosphate
nucleotide and
GTO analogues to
inhibit viral DNA
polymerase
Acyclovir (HSV),
Famciclovir
(VZV),
Ganciclovir (EBV,
CMV)
Loss of viral
thymidine
kinase, altered
CMV DNA
polymerase
Neutropenia,
thrombo-
cytopenia, crystal-
induced renal
toxicity
Foscarnet-IV Pyrophosphate
analogue that
competitively
binds to viral DNA
polymerase to
inhibit viral
replication
Ganciclovir-
resistant CMV,
Acyclovir-
resistant HSV
Altered DNA
polymerase
Nephrotoxicity,
hypocalcemia

36. 3636
HIGHLY ACTIVE ANTIRETROVIRAL THERAPY (HAART)
PROTEASE
INHIBITORS
MECHANISM COVERAGE RESISTANCE TOXICITY
- Amprenavir
- Ataznavir
- Darunavir
- Lopinavir
- Ritonavir
- Indinavir
- Nelfinavir
Inhibit HIV-1 protease,
prevent cleavage of
polypeptide product
from mRNA translation
into functional
subunits; prevent viral
maturation
HIV-1/AIDS Multiple
genetic
mutations
GI upset (diarrhea,
vomiting),
lipodystrophy,
hyperglycemia,
hyperlipidemia,
nephrolithiasis
(Indinavir)
NUCLEOSIDE
REVERSE TR.
INHIBITORS
- Lamivudine
- Emcitrabine
- Zidovudine
- Tenofovir
- Didanosine
- Abacavir
- Stavudine
Nucleotide analogs
that require
intracellular
phosphorylation to
create triphosphate
nucleotide analogs;
inhibit viral reverse
transcriptase, causing
chain terminations and
disruption of viral
replication
HIV1, 2/AIDS,
Hepatitis-B
Multiple
genetic
mutations,
multifactorial
Mitochondrial
toxicity
(neuropathy,
pancreatitis,
hepatic steatosis
lipoatrophy),
lactic acidosis

37. 3737
HAART (continued)
NON-NRTI MECHANISM COVERAGE RESISTANCE TOXICITY
- Efavirenz
- Nevirapine
- Delavirdine
- Etravirine
- Rilpivirine
Allosteric inhibitors
of viral reverse
transcriptase,
decreasing affinity
for nucleosides and
disrupting viral
replication
HIV 1 / AIDS in
adults
Multiple
genetic
mutations
Rash, erythema
multiforme,
Stevens-Johnson
syndrome, toxic
epidermal
necrolysis, insomnia
FUSION
INHIBITORS
- Enfuvirtide
Bind to viral gp41
subunit on outer
envelope, blocking
conformational
change required to
bind w/ CD4 to
enter CD4+ cells
HIV 1 in adults Mutations in
gp41 (are used
in combined
therapy w/ NRTI
or NNRTI)
GI upset,
hypersensitivity,
increased risk for
bacterial
pneumonia
CCR5
RECEPTOR
ANTAGONISTS
- Maraviroc
Entry inhibitor
binding to co-
receptor CCR5
required for CD4
fusion to enter
CD4+ cells
HIV1, also in
allogeneic
bone-marrow
transplantatio
n for leukemia
Use of CXCR4 as
co-receptor
Rash, hepatoxicity
INTEGRASE
INHIBITORS
- Raltegravir
Prevents viral cDNA
complex
integration w/ host
cell DNA
HIV1 in
pediatric
patients
Multiple
genetic
mutations
Generally, well
tolerated (limited
studies)

38. 3838
ANTIFUNGALS
SYSTEMIC MECHANISM COVERAGE TOXICITY
- Amphotericin-B Binds ergosterol and
forms permeable pores in
the cell membrane. Only
a few organisms are
resistant because of the
reduced/modified
ergosterol
Clinically significant
yeasts (Candida,
Cryptococcus),
endemic mycoses
(Hystoplasma,
Blastomyces,
Coccidioides), molds
(Aspergillus)
Immediate effects
are GI upset, muscle
spasm, fever, chills;
long-term effects
include
hepatotoxicity,
anemia from renal
damage (decreased
erithropoietin)
- Flucytosine (5-FC) 5-FC is taken up by the
fungal cytosine
permease, & mobilized to
active form to inhibit
RNA/DNA synthesis
Cryptococcus, Candida,
Chromoblastomycosis
Colon flora can
convert to 5-FC to 5-
fluorouracil (5-FU)
which is toxic to
bone marrow
- Azoles Inhibit fungal CYP 450 to
block ergosterol
production
Broad coverage,
effective for dimorphic
fungi (Histoplasma,
Blastomyces,
Sporothirx),
onychomycosis
GI upset, rash,
visual
disturbances;
Voriconizole should
not be combined
with Cyclosporine
-Echinocandins Disruption of fungal cell
wall via inhibition of
β(1,3)-glucan synthesis
Candida, neutropenic
fever, disseminated
Aspergillosis
Minor GI upset; do
not combine
Caspofungin with
Cyclosporin

39. 3939
ANTIFUNGALS (continued)
ORAL MECHANISM COVERAGE TOXICITY
- Griseofulvin Deposits in the skin to
bind keratin to protect
from new infections
Dermatophytoses
only
Serum sickness
allergy, hepatitis,
interactions with
Warfarin and
Phenobarbital
- Terbinafine Keratophilic, and
fungicidal through
inhibition of squalene
epoxidase
Dermatophytosis,
especially
onychomycosis
Hepatotoxicity, GI
upset, headache
TOPICAL/ORAL
- Nystatin Like Amphotericin-B,
binds to ergosterol to
form pores in fungal cell
membranes
Candida (oral thrush,
vulvovaginitis,
intertriginious
infections)
Extremely toxic in
parenteral use

40. Antiparasitic Drugs: Scenarios
4040
A 5-year old girl complaints of anal itching that worsens at nights.
- The girl likely has Enterobiasis (“pinworm”) caused by Enterobius vermicularis. Home-
diagnostic is based on observing adult worms moving near the anus – better visualized
with a flashlight at nights. Eggs deposited near the anus can be picked up with a piece of
transparent tape (“Scotch tape test”) and evaluated under microscope. Treatment with
benzimidazole and preventive hygienic measures.
Two patients arrive at ER. One is a male treated a week ago for low extremity cellulitis,
who now presents with intermittently bloody diarrhea. The other is a female
presenting with intense vaginal pruritis with thin, odorous, greenish discharge and
motile flagellated organisms on wet prep.
- The first patient has Pseudomembranous Colitis, and the second has Trichomoniasis
Vaginalis (pelvic exam with specula would probably reveal “strawberry cervix”). Both are
treated with metronidazole.
You are dispatched by the Carter Foundation to volunteer in Ghana, Africa. A 12-year
old boy presents with fever and chills that developed after he noticed worms coming
out the skin of his dorsal feet, causing burning pain. History includes daily consumption
of pond water in poor sanitary environment.
- The boy suffers Dracunculiasis (Guinea worm disease, GWD). There is neither medication
nor vaccine for GWD. Once part of the worm begins to emerge from the blister or wound,
the rest of the worm can be pulled out a few centimeters each day by winding it around a
piece of gauze or a small stick. It usually takes weeks to remove one worm. NSAIDs (aspirin,
ibuprofen) can help alleviate pain and swelling. Antibiotics can help prevent secondary
bacterial infections. The worm can also be surgically removed by a trained doctor before a
blister forms.

41. Legal Disputes, Court Holdings
CASE1: Lent v. Good Samaritan Hospital 1
PROCEDURAL NARRATIVE: Plaintiff brought medical malpractice action seeking remedies for
personal and derivative damages premised upon the defendants' alleged negligent
departures from the accepted standards of medical care, in particular for failure to provide
informed consent during the care, and failure to timely diagnose Babesiosis and concurrent
Lyme disease which caused her undergo a prolonged treatment and spleenectomy, suffer
pulmonary embolism and require mechanical ventilation, which in turn worsened her
cardiac function.
HOLDING: The proponent of a summary judgment motion must make a prima facie showing
of entitlement to judgment as a matter of law, tendering sufficient evidence to eliminate any
material or triable issues of fact from the case.
JURISDICTION: Friends of Animals v Associated,2
Sillman v Twentieth Century-Fox Film
Corporation3
DISPOSITION: Defendants' motion for summary judgment was granted due to the plaintiff's
discontinuance of the action.
REASONING: In the plaintiffs' opposing papers, counsel had affirmed that a Stipulation of
Discontinuance had been provided by the plaintiffs, pursuant to CPLR 3217.
1) NY Slip Op 32736 - NY: Supreme Court (2012)
2) 46 NY2d 1065, 416 NYS2d 790 (1979)
3) 3 NY2d 395, 165 NYS2d 498 (1957) 4141

42. 4242
CASE2: Kurzner v. Sanders 4
NARRATIVE: Plaintiff brought a malpractice cause of action, claiming that defendant (a
board-certified ophthalmologist) failed to diagnose and properly treat a fungal
infection in his left eye, erroneously prescribing steroids for a viral infection which
eventually worsened the underlying condition leading to permanent blindness of his
left eye. Defendant contended that the original diagnosis of herpetic infection and
stromal inflammation was correct, that no testing other than slit-lamp evaluation was
necessary, and that the proper medications were timely begun. As time went on, the
patient's eye was improving, nevertheless he developed a new problem known as
Wessley ring, an indication of immune response, and that increasing the use of steroid
medication was appropriate for that condition. At the initial visit, there was no
evidence of satellite lesions, which are highly suggestive of fungal infections.
PROCEDURAL HISTORY: In the appeal, plaintiff asserted four assignments of error
derived from the jury verdict upon his medical malpractice claim.
HOLDING: The jury instruction on the "honest mistake in clinical judgment" was
prejudicial and erroneous.
JURISDICTION: Becker v. Lake Cty. Mem. Hosp. West ,5
DISPOSITION: Judgment of the Trial Court was reversed and the case was remanded
for a new trial.
REASONING: The jury instruction was wrong because it changed the standard of care
from an objective to a subjective one.
4) 89 Ohio App.3d 674 (1993)
5) 53 Ohio St.3d 202, 560 N.E.2d 165 (1990)

43. CASE3: United States v. Reimer 6
NARRATIVE: The relator was a temporary visitor from Europe, who upon the arrival was
subjected to medical examination. It was found that she was afflicted with a contagious
disease, ringworm of the toenails, based on which the board of special inquiry at Ellis
Island ordered her exclusion. The relator undertook an appeal to the Secretary of Labor.
The Secretary dismissed the appeal and declined to admit her temporarily under the
power reposed in her by 8 U.S.C.A. § 136(q).
PROCEDURAL HISTORY: A writ of habeas corpus was issued to try the relator's claim that
she is being excluded from the country unlawfully. In this writ she did not dispute the
presence of disease; rather she insisted that her disease was neither loathsome nor
dangerous and that the board's refusal to reopen the case deprived her of a fair hearing.
HOLDING: By act of Congress ( 8 U.S.C.A. §§136, 152) aliens afflicted "with a loathsome
or dangerous contagious disease" are barred from entering the United States. It also
provides that boards of special inquiry appointed by the commissioner of immigration or
inspector in charge at the various ports shall have authority to determine whether an
alien shall be allowed to land or shall be excluded.
JURISDICTION: U. S. ex rel. Vajtauer v. Commissioner7
DISPOSITION: The writ was dismissed.
REASONING: The medical certificate on arrival showed that the alien was afflicted with a
loathsome or dangerous contagious disease.
6) 89 Ohio App.3d 674 (1993)
7) 273 U.S. 103, 47 S. Ct. 302, 71 L.Ed. 560. (1929)
4343