Empiric Treatment:
Pneumonia
Overview of Pneumonia
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What is
pneumonia?
• Pneumonia is an inflammatory illness of the
lung.
Frequently, pneumonia is described as lung parenchyma/alveolar
(microscopic air-filled sacs of the lung responsible for absorbing
oxygen from the atmosphere) inflammation and (abnormal)
alveolar filling with fluid.
What Causes
Pneumonia?
• Pneumonia can result from a variety of
causes, including infection with bacteria,
viruses, fungi, or parasites, and chemical or
physical injury to the lungs.
Pneumonia
• The alveoli are tiny air sacs within the
lungs where the exchange of oxygen
and carbon dioxide takes place.
• Bronchiole: A tiny tube in the air conduit system
within the lungs that is a continuation of the
bronchi and connects to the alveoli (the air sacs
where oxygen exchange occurs.
• Bronchiole is the diminutive of bronchus, from
the word bronchos by which the Greeks referred
to the conduits to the lungs.
Symptoms of
Pneumonia
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Fever
Chills
Cough
Pleurisy: inflamed membranes around
the lungs
• Dyspnea: Difficult or labored breathing;
shortness of breath
Diagnosis of Pneumonia
• Pneumonia usually produces distinctive
sounds; these abnormal sounds are
caused by narrowing of airways or filling
of the normally air-filled parts of the lung
with inflammatory cells and fluid, a
process called consolidation.
Diagnosis of Pneumonia
• In most cases, the diagnosis of pneumonia is
confirmed with a chest x-ray.
• For most bacterial pneumonias, the involved
tissue of the lung appears on the x-ray as a dense
white patch (because the x-ray beam does not get
through), compared with nearby healthy lung
tissue that appears black (because the x-rays get
through easily, exposing the film).
• Viral pneumonias typically produce faint, widely
scattered white streaks or patches.
Two Types of Pneumonia
• Community-Acquired Pneumonia
(CAP): individual residing in their homes
• Hospital-Acquired Pneumonia (HAP):
individuals residing in hospitals
Community-Acquired
Pneumonia
• Typical: Sudden onset of fever, chills,
pleuritic chest pain, productive cough
– Streptococcus pneumoniae
– Haemophilus influenzae
• Atypical: often preceded by mild respiratory
illness
– Legionella spp.
– Mycoplasma pneumoniae
– Chlamydophila pneumoniae
CAP: typical
Streptococcus pneumoniae
Gram +
Usually susceptible to penicillin
Streptococcus pneumoniae
Treatment of Streptococcus
pneumoniae
Ampicillin
• Penicillin G (high doses)
• Aminopenicillins: Ampicillin (high doses)
Treatment of Penicillin-resistant
Streptococcus pneumoniae
• Second Generation Cephalosoporins:
Cefuroxime
• Third Generation Cephalosporins:
Cefotaxime, Ceftriaxone
• Quinolones: Moxifloxacin, Levofloxacin
• Vancomycin
• Macrolides/ketolines: Telithromycin
Haemophilus influenzae
Haemophilus influenzae
•Haemophilic means ‘blood loving’. The organism
requires a blood-containing medium for growth
•Influenzae: The bacterium often attacks the lungs
of a patient with viral influenza.
• Since the organism was
frequently isolated from
the lungs of patients
during the 1890 and 1918
influenza pandemics,
scientists incorrectly
concluded that the
bacterium was the
causative agent.
Haemophilus influenzae
Haemophilus influenzae
Treatment of Infections Caused
by Haemophilus influenzae
• Aminopenicillins + b-lactamase inhibitor:
– Amoxicillin/clavulanate
– Ampicillin/sulbactam
• Second-generation cephalosporin
– Cefuroxime
• Third-generation cephalosporin
– Ceftriaxone
– Cefotaxime
Bacterial Causes of CAP
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Streptococcus pneumoniae
Haemophilus influenzae
Legionella spp
Mycoplasma pneumoniae
Other aerobic Gram-neg
Chlamydophila pneumoniae
Staphylococcus aureus
16-60%
3-38%
2-30%
1-20%
7-18%
6-12%
2-5%
Treatment of CAP
Treatment of CAP
• Mild
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Macrolide (azithromycin, clarithromycin)
Macrolide + b-lactam
Doxycycline
Quinolone (moxifloxacin, levofloxacin,
gemifloxacin)
• Severe
 b-lactam + macrolide
 b-lactam + quinolone
Treatment of CAP
• Severe
 b-lactam + macrolide
 b-lactam + quinolone
HAP is also divided into two
classes:
• Early onset HAP: occurs within first five
days of hospitalization
• Late onset HAP: occurs after 5 days of
hospitalization
Bacterial Causes of
Early Onset HAP
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Methicillin-sensitive Staphylococcus aureus
Haemophilus influenzae
Enterobacteriaceae
Streptococcus pneumoniae
29-35%
23-33%
5-25%
7-23%
Bacterial Causes of Late
Onset HAP
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Pseudomonas aeruginosa
Acinetobacter spp.
Enterobacteriaceae
Methicillin-resistant S. aureus
39-64%
6-26%
16-31%
0-2%
Treatment of Early Onset HAP
Ceftriaxone = 3rd gen. cephalosporin
Treatment of Early Onset HAP
• Ceftriaxone
• Quinolone (Levofloxacin, Moxiflocacin,
Ciprofloxacin)
• Ampicillin/sulbactam
• Ertapenem
Treatment of Late Onset HAP
Treatment of Late Onset HAP
Use a combination regimen from the first and second
categories below:
• Antipseudomonal cephalosporin: ceftazidime,
cefepime
• Or Carbapenem: Imipenem, Meropenem
• Or Extended spectrum penicillin/b-lactamase
inhibitor: piperacillin/tazobactam
++++
• Quinolone (ciprofloxacin, levofloxacin)
• Or Aminoglycoside (gentamicin, tobramycin,
amikacin)
• If MRSA is suspected, add: Vancomycin or
Linezolid
Urinary Tract Infections
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Urinary System
Mild and Severe UTI’s
• Mild
– Involve only the urethra and bladder
– Referred to as “acute cystitis”
– Symptoms include
• dysuria (painful urination)
• urinary frequency
• hematuria (blood in urine)
Severe UTI’s
• Severe
– Infection of the upper urinary tract involves the
spread of bacteria to the kidney
– Symptoms include fever, chills, nausea,
vomiting and flank pain
– Called “pyelonephritis”
‘Complicated’ and
‘Uncomplicated’ UTI’s
• Uncomplicated: Less likely to recur.
Occur in young, healthy, nonpregnant
women
• Complicated: All other UTI’s. More likely
to recur.
Bacterial Causes of
Uncomplicated UTI’s
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Escherichia coli
Proteus mirabilis
Staphylococcus saprophyticus
Klebsiella spp.
Other Enterobacteriaceae
53-79%
4-5%
3%
2-3%
3%
Treatment of Uncomplicated Acute Cystitis
Treatment of Uncomplicated
Acute Cystitis
• Oral trimethoprim-sulfamethoxazole
• Oral quinolones (ciprofloxacin, levofloxacin)
Treatment of Uncomplicated Acute Pyelonephritis
Amoxicillin, an aminopenicillin
Gentamycin, an aminoglycoside
Treatment of Uncomplicated Acute Pyelonephritis
• Quinolones: Ciprofloxacin, levofloxacin
• Third generation cephalosporins: Ceftriaxone,
cefotaxime, ceftizoxime
• If Gram positive organisms seen in urine:
– Aminopenicillin (amoxicillin)
– Aminopenicillin + b-lactamase inhibitor: (amoxicillin +
clavulanate)
– Aminopenicillin + aminoglycoside (ampicillin +
gentamicin)
Treatment of Complicated
Urinary Tract Infections
Treatment of Complicated
Urinary Tract Infections
• Fourth generation cephalosporins
(cefepime)
• Quinolones: Ciprofloxacin, Levofloxacin
• If Gram-positive bacteria seen in urine:
– Aminopenicillin + aminoglycoside:
Ampicillin + gentamicin
Pelvic Inflammatory Disease
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Female Reproductive Organs
PID is the general term for an infection that
has traveled through the vagina, to the
uterus, and then to other parts of the pelvis
Symptoms of
PID
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Abnormal bleeding
Dyspareunia (pain during sexual intercourse)
Vaginal discharge
Lower abdominal pain
Fever
chills
Bacterial Causes of PID
• Neisseria gonorrhoeae
27-56%
• Chlamydia trachomatis
22-31%
• Anaerobic and facultative bacteria
(Bacteria that can live under aerobic or
anaerobic conditions)
20-78%
Treatment of PID
Treatment of PID
• Mild to Moderate Disease
– Oral quinolone: Levofloxacin, ofloxacin
+ oral metronidazole
– Single IM dose of cephalosporin
+ oral doxycycline
+ oral metronidazole
Treatment of PID
Those that are severely ill should be admitted to the
hospital and treated initially with intravenous agents.
• Severe Disease (regimen 1)
– Cephalosporin with anaerobic activity (cefotetan,
cefoxitin)
+ doxycycline (active against atypical C. trachomatis)
• Severe Disease (regimen 2)
– Clindamycin (active against C. trachomatis and against
many anaerobes)
+ Gentamicin (effective against Gram-negative N. gonorrhoeae)
Meningitis
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Meningitis
• Meningitis is the inflammation of the
protective membranes covering the central
nervous system, known collectively as the
meninges.
• Meningitis may develop in response to a
number of causes, most prominently
bacteria, viruses and other infectious
agents, but also physical injury, cancer, or
certain drugs.
• Meninges: the membranes that envelope
the brain and the spinal cord.
Symptoms of Meningitis
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Headache
Fever
Neck stiffness
Altered mental status
Photophobia
Nausea
Vomiting
Seizures
• The most important test used to diagnose meningitis
is the lumbar puncture (commonly called a spinal
tap).
• Lumbar puncture (LP) involves the insertion of a thin
needle into a space between the vertebrae in the
lower back and the withdrawal of a small amount of
CSF.
Lumbar puncture
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Diagnosis of Meningitis
• The CSF is then examined under a microscope to
look for bacteria or fungi.
• Normal CSF contains set percentages of glucose
and protein.
• These percentages will vary with bacterial, viral, or other
causes of meningitis.
• For example, bacterial meningitis causes a greatly lower
than normal percentage of glucose to be present in CSF, as
the bacteria are essentially "eating" the host's glucose, and
using it for their own nutrition and energy production.
Diagnosis of Meningitis
• Normal CSF should contain no infection-fighting
cells (white blood cells), so the presence of white
blood cells in CSF is another indication of
meningitis.
• Some of the withdrawn CSF is also put into
special lab dishes to allow growth of the
infecting organism, which can then be
identified more easily.
• Special immunologic and serologic tests may
also be used to help identify the infectious
agent.
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Bacterial Causes of Acute
Bacterial Meningitis
• 0 - 3 months:
– Streptococcus agalactiae
– Escherichia coli
– Listeria monocytogenes
Bacterial Causes of Acute
Bacterial Meningitis
• 3 month - 6 yrs:
– Neisseria meningitidis
– Streptococcus pneumoniae
– Haemophilus influenzae
Bacterial Causes of Acute
Bacterial Meningitis
• 16 yrs - 50 yrs
– Streptococcus
pneumoniae
– Neisseria
meningitidis
Bacterial Causes of Acute
Bacterial Meningitis
• > 50 yrs
– Streptococcus pneumoniae
– Listeria monocytogenes
– Aerobic Gram-negative bacilli
Treatment of Bacterial Meningitis
Treatment of Bacterial Meningitis
• Third-generation cephalosporins: cefotaxime,
ceftriaxone
+ Vancomycin (coverage against resistant Streptococcus
pneumoniae)
• If patient < 3 months or > 50 years
Same as above, but also
Add ampicillin to provide coverage of L.
monocytogenes and S. agalactiae.
Cellulitis
Cellulitis is an inflammation of the connective tissue
underlying the skin, that can be caused by a bacterial
infection.
Cellulitis
Bacterial Causes of Cellulitis
• Staphylococcus aureus
• Streptococcus pyogenes
• Other streptococci
13-37%
4-17%
1-18%
Treatment of Cellulitis
Treatment of Cellulitis
• Mild Disease (oral formulations)
– Antistaphylococcal penicillins (Dicloxacillin)
– First Generation Cephalosporins
(Cephalexin, Cefadroxil)
– Clindamycin
– Macrolides (Erythromycin, azithromycin,
clarithromycin)
Treatment of Cellulitis
• Severe Disease (intravenous formulations)
– Antistaphylococcal penicillins (Nafcillin, oxacillin)
– First-generation cephalosporins (cefazolin)
– Clindamycin
Treatment of Cellulitis
• If MRSA is suspected
– Vancomycin
– Linezolid
– Daptomycin
– Tetracyclines (Tigecycline, doxycycline)
– Sulfa drugs (Trimethoprimsulfamethoxazole)
– Clindamycin
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Symptoms of Otitis Media
• Otalgia (ear pain)
• Hearing Loss
• Irritability
• Anorexia
• Apathy
• Fever
• Swelling around the ear
• Otorrhea (discharge from the affected ear)
Bacterial Causes of Acute
Otitis Media
• Streptococcus pneumoniae
• Haemophilus influenzae
• Moraxella catarrhalis
25-50%
15-30%
3-20%
Treatment of Acute Otitis Media
Treatment of Acute Otitis
Media
• First Line Therapy
– High Dose Amoxicillin
• If Mild Allergy to Penicillin
– Cefdinir, Cefpodoxime, Cefuroxime axetil
• If Type 1 Hypersensitivity Allergic
Reaction
– Macrolide (Azithromycin, Clarithromycin,
Erythromycin with sulfisoxazole)
Sulfmethoxazole
Sulfisoxazole
Used in combination
with Erythromycin
Used in combination with
Trimethoprim
(co-trimoxazole)
Infective Endocarditis
Causes of
Endocarditis
• There are many ways that bacteria can
enter the bloodstream and cause
endocarditis. Even a small cut can
enable bacteria that normally live on the
skin to enter the bloodstream.
• In some cases, this occurs during a dental
or surgical procedure. In many cases,
however, it is not clear how the bacteria
first got into the bloodstream.
Symptoms of Endocarditis
• Symptoms are non-specific, making
endocarditis difficult to diagnose:
• Fatigue
• Malaise
• Weakness
• Weight loss
• Fever
• Chills
• Dyspnea on exertion (shortness of breath)
Bacterial
Causes of
Endocarditis
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Viridans group streptococci
18-48%
Staphylococcus aureus
22-32%
Enterococci
7-11%
Coagulase-negative staphylococci 7-11%
HACEK organisms
2-7%
Viridans Group streptococci
• Viridans streptococcus are alpha-hemolytic,
normal flora of the oral, respiratory tract, and
GI mucosa.
• They are the major cause of bacterial
endocarditis in people with damaged
heart valves. They may enter the blood
stream after dental procedures.
HACEK Organisms
• A HACEK organism is one of a set of slow-growing
Gram negative bacteria that form a normal part of
the human flora. They are a frequent cause of
endocarditis in children.
• The name is formed from their initials:
• Haemophilus aphrophilus, Haemophilus
parainfluenzae and Haemophilus paraphrophilus
• Actinobacillus actinomycetemcomitans
• Cardiobacterium hominis
• Eikenella corrodens
• Kingella kingae
Empiric Therapy for Infective
Endocarditis
• Vancomycin + Gentamicin
– Vancomycin is effective against S. aureus and
viridans group streptococci
– When used in combination with Gentamicin,
activity is extended to the majority of enterococcal
strains
• Even intensive therapy may not be
sufficient, and surgical intervention is
often required
• Despite intensive antibiotic therapy,
mortality remains high: 20-25%.
Prosthetic Valve Endocarditis
• Many cases of endocarditis are associated
with prosthetic valves in the heart
• Sometimes these infections occur within two
months after the valve is installed and are
thus thought to be hospital acquired
• Sometimes they occur 6-20 month after
surgery and are thus thought to be
community acquired
Treatment of Prosthetic Valve
Endocarditis
• Vancomycin + Gentamicin + Rifampin
– With or without cefepime or ceftriaxone
Intravascular-Related
Catheter Infections
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• 200,000 catheter-related infections
occur each year in the U.S.
• Should be suspected in anyone with an
intravascular catheter and a fever of
unclear etiology.
• Diagnosis may involve:
– Removal and culture of the catheter
– Growth of bacteria from blood cultures
What type of bacteria cause
catheter-related infections?
• Skin flora, including:
– Staphylococcus epidermidis 32-41%
– Staphylococcus aureus 5-14%
– Enteric Gram-negative bacilli 5-11%
– Psuedomonas aeruginosa 4-7%
Treatment of Intravascular
Catheter-related Infections
Treatment of Catheter Related
Infections
• Hospital setting where MRSA is uncommon
– Antistaphylocccal penicillin: Nafcillin, Oxacillin
• Hospital setting where MRSA is common
– Vancomycin
• Immunocompromised or severely ill patient
– Add cephalosporin to initial antibiotic regimen
– Ceftazidime, cefepime
Intra-Abdominal Infections
Causes of Intra-abdominal
infections
• Usually caused by contamination of the
usually sterile abdomen with microbial
flora of the bowel
• Can be quite severe, leading to sepsis
and death
Bacterial Causes of Intraabdominal Infections
• Gram-negative bacilli
– Escherichia coli 32-61%
– Enterobacter spp. 8-26%
– Klebsiella spp.
6-26%
– Proteus spp.4-23%
Bacterial Causes of Intraabdominal Infections
• Gram-positive cocci
– Enterococci 18-24%
– Streptococci 6-55%
– Staphylococci 6-16%
Bacterial Causes of Intraabdominal Infections
• Anaerobic bacteria
– Bacteroides spp.
– Clostridium spp.
Treatment of Intra-abdominal
Infections
• Due to their polymicrobial nature, the
antibiotic regimen must be very broad
spectrum, including Gram-negative
bacilli, Gram-positive cocci, and
anaerobic bacteria
Treatment of Intra-Abdominal
Infections
 b-Lactam/b-lactamase inhibitor
combinations (piperacillin/tazobactam)
• Carbapenems (imipenem, meropenem)
• Aminoglycoside (gentamicin,
tobramycin, amikacin)
+ metronidazole
• Ciprofloxacin + metronidazole
Treatment of Intra-abdominal
Infections