This document discusses various classifications of infectious diseases and drug therapy for treating them. It describes how infectious diseases can be classified based on factors like onset/duration (acute, chronic, etc.), location (local, focal, systemic), items present in the bloodstream (septicaemia, bacteremia, etc.), and epidemiological patterns (endemic, epidemic, pandemic, etc.). It then provides details on different classes of antibiotics used to treat bacterial infections, including beta-lactam antibiotics (penicillins, cephalosporins, carbapenems, monobactams) and chloramphenicol. It notes challenges like increasing antibiotic resistance.

1. DRUG THERAPY OF
INFECTIOUS DISEASES

2. Classification of infectious diseases
 •According to onset and duration
 •According to location
 •According to item present
 •According to sequence of appearance
 •According to epidemiological factors

3. Classifications according to onset and duration
 Acute disease -- Rapid onset and short
duration. E.g. common cold, measles
 Chronic disease -- Slower onset and longer
duration. eg TB, leprosy
 Subchronic disease -- ermediate to acute
and chronic both in onset and duration. eg
gingivitis
 Latent disease -- One characterized by
periods of activity erspersed with periods of
inactivity. E.g.: malaria, herpes simplex.

4. Classification according to location
 Local infection --
Confined to a specific
area of the body. E.g.:
cystitis, vaginitis,
myocarditis.
 Focal infection --
Infection that started in
one place and later on
spread to other areas.
E.g. tuberculosis, sinus
infection, infected
tooth.
 Systemic (generalized)
infection - Occurring
throughout the body

5. Medical Lecture Notes – All Subjects
USMLE Exam (America) – Practice

6. Classifications according to item present
 Septicemia -- A microbe is present in the blood, is
continuously being delivered from tissues to blood and
is actively multiplying in the blood. Typical of systemic
diseases. Often fatal.
 Bacteremia -- Presence of bacteria in the blood
 Viremia -- Presence of virus in the blood of the body
 Pyemia -- Poisoning of the blood by pus-producing
bacteria released from an abscess
 Toxaemia -- Presence of bacterial toxins in the blood.
Can result in fever, diarrhea and vomiting.

7. Classification according to sequence of appearance
 Primary infection - Initial infection in a healthy person
 Secondary infection - Occurs after primary infection
 Superinfection - A secondary infection due to the
destruction of the protective normal flora of the body
by the use of a broad spectrum antibiotic
Also defined as a secondary infection facilitated by a
primary infection e.g. HIV and AIDS

8. Epidemiological factors - mode of appearance, number
of cases, trends of diseases in populations
Classifications according to epidemiological
factors
 Endemic disease (endemia) - Present regularly in particular
area of the world, and total number and severity are low
 Ecdemic disease (ecdemia) - A foreign disease brought to a new
area by travelers or immigrants from a foreign country
 Pandemic disease (pandemia) - A disease that affects many
people and which occurs across neighboring cities, countries or
continents. Affects many people.
 Epidemic disease (epidemia) - Appears suddenly, affects many
people and is confined to a particular, often the same, area.
Morbidity rate and mortality rate above what is normal.
 Sporadic disease (epidemia) - Appears suddenly, in a random
and unpre-dictable manner, affects only a few people, and
limited to a few, usually unrelated, places.
 Outbreak - Few cases, often related in time and location, and
sharing same manifestations

9. Threat of emerging infectious
diseases
Due to constant changes in our lifestyles and
environments,
there are constantly new diseases that people
are susceptible to, making protection from the threat
of
infectious disease urgent. Many new contagious
diseases
have been identified in the past 30 years, such as
AIDS, Ebola, and hantavirus. Increased travel
between
continents makes the worldwide spread of disease a
bigger
concern than it once was. Additionally, many
common
infectious diseases have become resistant to known

10. Problems of antibiotic resistance
Because of the overuse of antibiotics, many bacteria
have developed a resistance to common antibiotics.
This
means that newer antibiotics must continually be
developed
in order to treat an infection. However, further
resistance seems to come about almost
simultaneously.
This indicates to many scientists that it might become
more and more difficult to treat infectious diseases.
The
use of antibiotics outside of medicine also contributes
to
increased antibiotic resistance. One example of this is
the
use of antibiotics in animal husbandry. These negative

11. Beta-Lactam Antibiotics

12. A penicillin culture

13. Cephalosporins and cephamycins are
similar to penicillins chemically, in
mechanism of action, and in toxicity.
Cephalosporins are more stable than
penicillins to many bacterial
-lactamases and therefore usually have
a broader spectrum of activity.
Cephalosporins are not active against
enterococci and Listeria
monocytogenes.

14.  These are drugs with a monocyclic -lactam ring . They are
relatively resistant to
 lactamases and active against gram-negative rods (including
pseudomonas and serratia). They have
 no activity against gram-positive bacteria or anaerobes.
Aztreonam is the only monobactam
 available in the USA. It resembles aminoglycosides in its
spectrum of activity. Aztreonam is given
 intravenously every 8 hours in a dose of 1–2 g, providing peak
serum levels of 100 g/mL. The
 half-life is 1–2 hours and is greatly prolonged in renal failure.
 Penicillin-allergic patients tolerate aztreonam without reaction.
Occasional skin rashes and
 elevations of serum aminotransferases occur during
administration of aztreonam, but major toxicity
 has not yet been reported. The clinical usefulness of aztreonam
has not been fully defined.

15.  These substances resemble -lactam molecules (Figure 43–7) but
themselves have very weak
 antibacterial action. They are potent inhibitors of many but not all
bacterial lactamases and can
 protect hydrolyzable penicillins from inactivation by these enzymes.
-Lactamase inhibitors are
 most active against Ambler class A lactamases (plasmid-encoded
transposable element [TEM] -
 lactamases in particular) such as those produced by staphylococci, H
influenzae, N gonorrhoeae,
 salmonella, shigella, E coli, and K pneumoniae. They are not good
inhibitors of class C -
 lactamases, which typically are chromosomally encoded and inducible,
produced by enterobacter,
 citrobacter, serratia, and pseudomonas, but they do inhibit
chromosomal lactamases of legionella,
 bacteroides, and branhamella.

16.  The indications for penicillin- -lactamase inhibitor combinations
are empirical therapy for
 infections caused by a wide range of potential pathogens in
both immunocompromised and
 immunocompetent patients and treatment of mixed aerobic and
anaerobic infections, such as intraabdominal
 infections. Doses are the same as those used for the single
agents except that the
 recommended dosage of piperacillin in the piperacillin-
tazobactam combination is 3 g every 6
 hours. This is less than the recommended 3–4 g every 4–6
hours for piperacillin alone, raising
 concerns about the use of the combination for treatment of
suspected pseudomonal infection.
 Adjustments for renal insufficiency are made based on the
penicillin component.

17. The carbapenems are structurally related to beta-lactam
antibiotics. Ertapenem, imipenem, and meropenem are
licensed for use in the USA. Imipenem has a wide spectrum
with good activity against many gram-negative rods,
including Pseudomonas aeruginosa, gram-positive
organisms, and anaerobes. It is resistant to most
lactamases but not metallo- lactamases. Enterococcus
faecium, methicillin-resistant strains of staphylococci,
Clostridium difficile,
Burkholderia cepacia, and Stenotrophomonas maltophilia are
resistant. Imipenem is inactivated by dehydropeptidases in
renal tubules, resulting in low urinary concentrations.
Consequently, it is administered together with an inhibitor
of renal dehydropeptidase, cilastatin, for clinical use.
Meropenem is similar to imipenem but has slightly greater
activity against gram-negative aerobes and slightly less
activity against gram-positives. It is not significantly
degraded by renal
dehydropeptidase and does not require an inhibitor.
Ertapenem is less active than meropenem or imipenem against
Pseudomonas aeruginosa and acinetobacter species. It is
not degraded by renal dehydropeptidase.

18. The usual dose of imipenem is 0.25–0.5 g given intravenously every 6–
8 hours (half-life 1 hour). The usual adult dose of meropenem is 1 g
intravenously every 8 hours. Ertapenem has the longest half-life (4
hours) and is administered as a once-daily dose of 1 g intravenously
or intramuscularly. Intramuscular ertapenem is irritating, and for that
reason the drug is formulated with 1% lidocaine for
administration by this route. A carbapenem is indicated for infections
caused by susceptible organisms that are resistant to other available
drugs and for treatment of mixed aerobic and anaerobic infections.
Carbapenems are active against many highly penicillin-resistant
strains of pneumococci. A carbapenem is the beta- lactam antibiotic
of choice for treatment of enterobacter infections, since it is resistant
to destruction by the lactamase produced by these organisms.
Strains of Pseudomonas aeruginosa may rapidly develop resistance
to imipenem or meropenem, so simultaneous use of an
aminoglycoside is recommended for infections caused by those
organisms. Ertapenem is insufficiently active against P aeruginosa
and should not be used to treat infections caused by that organism.
Imipenem or meropenem with or without an aminoglycoside may be
effective treatment for febrile neutropenic patients.

19. Chloramphenicol is a potent inhibitor of microbial protein
synthesis. It binds reversibly to the 50S subunit of the
bacterial ribosome.
Because of potential toxicity, bacterial resistance, and
the availability of other effective drugs (eg,
cephalosporins), chloramphenicol is all but obsolete as a
systemic drug. It may be considered for treatment of
serious rickettsial infections, such as typhus or Rocky
Mountain spotted fever, in children for whom tetracyclines
are contraindicated, ie, those under 8 years of age. It is
an alternative to a -lactam antibiotic for treatment of
meningococcal meningitis occurring in patients who have
major hypersensitivity reactions to penicillin or bacterial
meningitis caused by penicillinresistant strains of
neumococci. The dosage is 50–100 mg/kg/d in four
divided doses.
Chloramphenicol is occasionally used topically in the
treatment of eye infections because of its wide
antibacterial spectrum and its penetration of ocular
tissues and the aqueous humor. It is ineffective for

20. Newborn infants lack an effective glucuronic acid
conjugation mechanism for the degradation and
detoxification of chloramphenicol. Consequently,
when infants are given dosages above 50
mg/kg/d, the drug may accumulate, resulting in
the gray baby syndrome, with vomiting,
flaccidity, hypothermia, gray color, shock, and
collapse. To avoid this toxic effect,
chloramphenicol should be
used with caution in infants and the dosage limited
to 50 mg/kg/d or less (during the first week of
life) in full-term infants and 25 mg/kg/d in remature
infants.

21. Tetracyclines are broad-spectrum
bacteriostatic antibiotics that inhibit protein
synthesis. They are active against many gram-
positive and gram-negative bacteria, including
anaerobes, rickettsiae, chlamydiae, mycoplasmas,
and L forms; and against some protozoa, eg,
amebas. The antibacterial activities of most
tetracyclines are similar except that tetracycline-
resistant strains may remain susceptible to
doxycycline or minocycline, drugs that are less
rapidly transported by the pump that is
responsible for resistance

22. A tetracycline is the drug of choice in infections with
Mycoplasma pneumoniae, chlamydiae, rickettsiae, and some
spirochetes. They are used in combination regimens to treat
gastric and duodenal ulcer disease caused by Helicobacter
pylori. In cholera, tetracyclines rapidly stop the shedding of
vibrios, but tetracycline resistance has appeared during
epidemics. Tetracyclines remain effective in most chlamydial
infections, including sexually transmitted diseases.
Tetracyclines are no longer recommended for treatment of
gonococcal disease because of resistance. A tetracycline—
usually in combination with an aminoglycoside—is indicated
for plague, tularemia, and brucellosis. Tetracyclines are
sometimes employed in the treatment of protozoal infections,
eg, those due to Entamoeba histolytica or Plasmodium
falciparum. Other uses include treatment of acne,
exacerbations of bronchitis, community-acquired pneumonia,
Lyme disease, relapsing fever, leptospirosis, and some
nontuberculous mycobacterial infections (eg, Mycobacterium
marinum). Tetracyclines formerly were used for a variety of
common infections, including bacterial gastroenteritis,
pneumonia (other than mycoplasmal or chlamydial
pneumonia), and urinary tract infections. However, many

23. Erythromycin
Clarithromycin (is derived from erythromycin)
Azithromycin (differs from erythromycin and clarithromycin
mainly in pharmacokinetic properties). The drug is
slowly released from tissues (tissue half-life of 2–4 days)
to produce an elimination half-life approaching 3 days.
These unique properties permit once-daily dosing and
shortening of the duration of treatment in many cases.
For example, a single 1 g dose of azithromycin is as
effective as a 7-day course of doxycycline for chlamydial
cervicitis and urethritis. Community-acquired
pneumonia can be treated with zithromycin given as a
500 mg loading dose, followed by a 250 mg single daily
dose for the next 4 days.
Ketolides (Telithromycin)

24. Aminoglycosides
Streptomycin, neomycin,
kanamycin, amikacin,
gentamicin, tobramycin,
sisomicin, netilmicin

25. Sulfonamides are infrequently used as single
agents. Formerly drugs of choice for infections
such as Pneumocystis jiroveci (formerly P carinii)
pneumonia, toxoplasmosis, nocardiosis, and
occasionally other bacterial infections, they have
been largely supplanted by the fixed drug
combination of trimethoprim-sulfamethoxazole.
Many strains of formerly susceptible species,
including meningococci, pneumococci,
streptococci, staphylococci, and gonococci, are
now resistant. Nevertheless, sulfonamides can be
useful for treatment of urinary tr

26. Sulfisoxazole and sulfamethoxazole are short- to
medium-acting agents that are used almost
exclusively to treat urinary tract infections. The usual
adult dosage is 1 g of sulfisoxazole four times daily or 1
g of sulfamethoxazole two or three times daily.
Sulfadiazine achieves therapeutic concentrations in
cerebrospinal fluid and in combination with
pyrimethamine is first-line therapy for treatment of acute
toxoplasmosis. Pyrimethamine, an antiprotozoal agent,
is a potent inhibitor of dihydrofolate reductase.
Sulfadoxine is available only as Fansidar, a combination
formulation with pyrimethamine, which is used as a
second-line agent in treatment for malaria

27. Sulfasalazine (salicylazosulfapyridine) is widely
used in ulcerative colitis, enteritis, and other
inflammatory bowel disease
Topical Agents
Sodium sulfacetamide ophthalmic solution or
ointment is effective treatment for bacterial
conjunctivitis and as adjunctive therapy for
trachoma. Mafenide acetate is used topically to
prevent bacterial colonization and infection of
burn wounds.

28. Fluoroquinolones
The important quinolones are synthetic
fluorinated analogs of nalidixic acid. They are active
against a variety of gram-positive and gram-negative
bacteria. Quinolones block bacterial DNA synthesis
by inhibiting bacterial topoisomerase II (DNA gyrase)
and topoisomerase IV.
Earlier quinolones (nalidixic acid, oxolinic acid,
cinoxacin) did not achieve systemic antibacterial
levels. These agents were useful only for treatment of
lower urinary tract infections.
Fluorinated derivatives (ciprofloxacin, levofloxacin,
and others) have greatly improved antibacterial
activity compared with nalidixic acid and achieve
bactericidal levels in blood and tissues.

29. Ciprofloxacin, enoxacin, lomefloxacin,
evofloxacin, ofloxacin, and pefloxacin comprise a
second group of similar agents possessing
excellent gram-negative activity and moderate to
good activity against grampositive bacteria.
Gatifloxacin, moxifloxacin, sparfloxacin, and
rovafloxacin comprise a third group of
fluoroquinolones with improved activity against
gram-positive organisms, particularly S
pneumoniae and to some extent staphylococci.

30. Antifungal AgentsAntifungal Agents
The antifungal drugs presently available
fall into several categories: systemic
drugs (oral or parenteral) for systemic
infections, oral drugs for mucocutaneous
infections, and topical drugs for
mucocutaneous infections.

31. Immunologic therapiesImmunologic therapies
Immunologic therapy is the treatment of diseaseImmunologic therapy is the treatment of disease
using medicines that boost the body’s natural immuneusing medicines that boost the body’s natural immune
response.response.
PurposePurpose
Immunologic therapy is used to improve theImmunologic therapy is used to improve the
immune system’s natural ability to fight such diseases asimmune system’s natural ability to fight such diseases as
cancercancer, hepatitis and, hepatitis and AIDSAIDS. These drugs may also be. These drugs may also be
used to help the body recover from immunosuppressionused to help the body recover from immunosuppression
resulting from such treatments asresulting from such treatments as chemotherapychemotherapy oror
radiation therapyradiation therapy..
DescriptionDescription

32. Immunologic therapiesImmunologic therapies
Most drugs in this category are synthetic versions ofMost drugs in this category are synthetic versions of
substances produced naturally in the body. In their naturalsubstances produced naturally in the body. In their natural
forms, these substances help defend the body againstforms, these substances help defend the body against
disease. For example, aldesleukin (Proleukin) is andisease. For example, aldesleukin (Proleukin) is an
artificiallyartificially
made form of interleukin-2, which helps whitemade form of interleukin-2, which helps white
blood cells work. Aldesleukin is administered to patientsblood cells work. Aldesleukin is administered to patients
with kidney cancers and skin cancers that have spread towith kidney cancers and skin cancers that have spread to
other parts of the body. Filgrastim (Neupogen) andother parts of the body. Filgrastim (Neupogen) and
sargramostim (Leukine) are versions of naturalsargramostim (Leukine) are versions of natural
substances calledsubstances called colony stimulating factorscolony stimulating factors , which, which
drive the bone marrow to make new white blood cells.drive the bone marrow to make new white blood cells.
Another type of drug, epoetin (Epogen, Procrit), is aAnother type of drug, epoetin (Epogen, Procrit), is a
synthetic version of human erythropoietin that stimulatessynthetic version of human erythropoietin that stimulates
the bone marrow to make new red blood cells.the bone marrow to make new red blood cells.
Thrombopoietin stimulates the production of platelets,Thrombopoietin stimulates the production of platelets,
disk-shaped bodies in the blood that are important indisk-shaped bodies in the blood that are important in
clotting.clotting.

33. Immunologic therapies cont’dImmunologic therapies cont’d
InterferonsInterferons are substances the body producesare substances the body produces
naturally using immune cells to fight infections andnaturally using immune cells to fight infections and
tumors. The synthetic interferons carry such brandtumors. The synthetic interferons carry such brand
names as Alferon, Roferon or Intron A. Somenames as Alferon, Roferon or Intron A. Some
of the interferons that are currently in use as drugsof the interferons that are currently in use as drugs
are Recombinant Interferon Alfa-2a, Recombinantare Recombinant Interferon Alfa-2a, Recombinant
Interferon Alfa-2b, interferon alfa-n1 and InterferonInterferon Alfa-2b, interferon alfa-n1 and Interferon
Alfa-n3. Alfa interferons are used to treatAlfa-n3. Alfa interferons are used to treat hairy cellhairy cell
leukemialeukemia,, malignant melanomamalignant melanoma and AIDS-and AIDS-
relatedrelated Kaposi’s sarcoma,Kaposi’s sarcoma, which is a form ofwhich is a form of
cancer. In addition interferons are also used for suchcancer. In addition interferons are also used for such
other conditions as laryngeal papillomatosis,other conditions as laryngeal papillomatosis,
genital wartsgenital warts and certain types of hepatitis.and certain types of hepatitis.

34. General precautions for all types ofGeneral precautions for all types of
immunologicimmunologic
therapytherapy
Regular physician visits are necessary duringRegular physician visits are necessary during
immunologic therapy treatment. This gives theimmunologic therapy treatment. This gives the
physician a chance to make sure the medicine isphysician a chance to make sure the medicine is
working and to check for unwanted side effects.working and to check for unwanted side effects.
Anyone who has had unusual reactions to drugsAnyone who has had unusual reactions to drugs
used in immunologic therapy should let theused in immunologic therapy should let the
physician know before resuming the drugs. Anyphysician know before resuming the drugs. Any
allergiesallergies to foods, dyes, preservatives, or otherto foods, dyes, preservatives, or other
substances should also be reported.substances should also be reported.