Empiric Treatment: Pneumonia

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Empiric Treatment Pneumonia
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Overview of Pneumonia

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What is pneumonia?

• Pneumonia is an inflammatory illness of the lung.

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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.
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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.

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Pneumonia

• The alveoli are tiny air sacs within the lungs
  where the exchange of oxygen and carbon dioxide
  takes place.

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• 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.

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Symptoms of Pneumonia

• Fever
• Chills
• Cough
• Pleurisy inflamed membranes around the lungs
• Dyspnea Difficult or labored breathing
  shortness of breath

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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.

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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.

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Two Types of Pneumonia

• Community-Acquired Pneumonia (CAP) individual
  residing in their homes
• Hospital-Acquired Pneumonia (HAP) individuals
  residing in hospitals

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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

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CAP typical

• Streptococcus pneumoniae
• Gram
• Usually susceptible to penicillin

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Streptococcus pneumoniae
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Treatment of Streptococcus pneumoniae
Ampicillin

• Penicillin G (high doses)
• Aminopenicillins Ampicillin (high doses)

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Treatment of Penicillin-resistant Streptococcus
pneumoniae

• Second Generation Cephalosoporins Cefuroxime
• Third Generation Cephalosporins Cefotaxime,
  Ceftriaxone
• Quinolones Moxifloxacin, Levofloxacin
• Vancomycin
• Macrolides/ketolines Telithromycin

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Haemophilus influenzae
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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.

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Haemophilus influenzae
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Haemophilus influenzae
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Treatment of Infections Caused by Haemophilus
influenzae

• Aminopenicillins b-lactamase inhibitor
• Amoxicillin/clavulanate
• Ampicillin/sulbactam
• Second-generation cephalosporin
• Cefuroxime
• Third-generation cephalosporin
• Ceftriaxone
• Cefotaxime

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Bacterial Causes of CAP

• Streptococcus pneumoniae 16-60
• Haemophilus influenzae 3-38
• Legionella spp 2-30
• Mycoplasma pneumoniae 1-20
• Other aerobic Gram-neg 7-18
• Chlamydophila pneumoniae 6-12
• Staphylococcus aureus 2-5

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Treatment of CAP
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Treatment of CAP

• Mild
• Macrolide (azithromycin, clarithromycin)
• Macrolide ?-lactam
• Doxycycline
• Quinolone (moxifloxacin, levofloxacin,
  gemifloxacin)
• Severe
• ?-lactam macrolide
• ?-lactam quinolone

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Treatment of CAP

• Severe
• ?-lactam macrolide
• ?-lactam quinolone

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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

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Bacterial Causes ofEarly Onset HAP

• Methicillin-sensitive Staphylococcus
  aureus 29-35
• Haemophilus influenzae 23-33
• Enterobacteriaceae 5-25
• Streptococcus pneumoniae 7-23

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Bacterial Causes of Late Onset HAP

• Pseudomonas aeruginosa 39-64
• Acinetobacter spp. 6-26
• Enterobacteriaceae 16-31
• Methicillin-resistant S. aureus 0-2

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Treatment of Early Onset HAP
Ceftriaxone 3rd gen. cephalosporin
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Treatment of Early Onset HAP

• Ceftriaxone
• Quinolone (Levofloxacin, Moxiflocacin,
  Ciprofloxacin)
• Ampicillin/sulbactam
• Ertapenem

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Treatment of Late Onset HAP
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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/?-lactamase
  inhibitor piperacillin/tazobactam
• Quinolone (ciprofloxacin, levofloxacin)
• Or Aminoglycoside (gentamicin, tobramycin,
  amikacin)
• If MRSA is suspected, add Vancomycin or Linezolid

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Urinary Tract Infections

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Urinary System
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Mild and Severe UTIs

• Mild
• Involve only the urethra and bladder
• Referred to as acute cystitis
• Symptoms include
• dysuria (painful urination)
• urinary frequency
• hematuria (blood in urine)

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Severe UTIs

• 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

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Complicated and Uncomplicated UTIs

• Uncomplicated Less likely to recur. Occur in
  young, healthy, nonpregnant women
• Complicated All other UTIs. More likely to
  recur.

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Bacterial Causes of Uncomplicated UTIs

• Escherichia coli 53-79
• Proteus mirabilis 4-5
• Staphylococcus saprophyticus 3
• Klebsiella spp. 2-3
• Other Enterobacteriaceae 3

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Treatment of Uncomplicated Acute Cystitis
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Treatment of Uncomplicated Acute Cystitis

• Oral trimethoprim-sulfamethoxazole
• Oral quinolones (ciprofloxacin, levofloxacin)

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Treatment of Uncomplicated Acute Pyelonephritis
Amoxicillin, an aminopenicillin
Gentamycin, an aminoglycoside
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Treatment of Uncomplicated Acute Pyelonephritis

• Quinolones Ciprofloxacin, levofloxacin
• Third generation cephalosporins Ceftriaxone,
  cefotaxime, ceftizoxime
• If Gram positive organisms seen in urine
• Aminopenicillin (amoxicillin)
• Aminopenicillin ?-lactamase inhibitor
  (amoxicillin clavulanate)
• Aminopenicillin aminoglycoside (ampicillin
  gentamicin)

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Treatment of Complicated Urinary Tract Infections
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Treatment of Complicated Urinary Tract Infections

• Fourth generation cephalosporins (cefepime)
• Quinolones Ciprofloxacin, Levofloxacin
• If Gram-positive bacteria seen in urine
• Aminopenicillin aminoglycoside Ampicillin
  gentamicin

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Pelvic Inflammatory Disease

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Female Reproductive Organs
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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
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Symptoms of PID

• Abnormal bleeding
• Dyspareunia (pain during sexual intercourse)
• Vaginal discharge
• Lower abdominal pain
• Fever
• chills

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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

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Treatment of PID
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Treatment of PID

• Mild to Moderate Disease
• Oral quinolone Levofloxacin, ofloxacin
• oral metronidazole
• Single IM dose of cephalosporin
• oral doxycycline
• oral metronidazole

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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)

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Meningitis

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Meningitis

• Meningitis is the inflammation of the protective
  membranes covering the central nervous system,
  known collectively as the meninges.

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• 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.

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• Meninges the membranes that envelope the
  brain and the spinal cord.

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Symptoms of Meningitis

• Headache
• Fever
• Neck stiffness
• Altered mental status
• Photophobia
• Nausea
• Vomiting
• Seizures

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• 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.

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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.

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• 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.

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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.

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• 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

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Bacterial Causes of Acute Bacterial Meningitis

• 3 month - 6 yrs
• Neisseria meningitidis
• Streptococcus pneumoniae
• Haemophilus influenzae

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Bacterial Causes of Acute Bacterial Meningitis

• 16 yrs - 50 yrs
• Streptococcus pneumoniae
• Neisseria meningitidis

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Bacterial Causes of Acute Bacterial Meningitis

• gt 50 yrs
• Streptococcus pneumoniae
• Listeria monocytogenes
• Aerobic Gram-negative bacilli

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Treatment of Bacterial Meningitis
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Treatment of Bacterial Meningitis

• Third-generation cephalosporins cefotaxime,
  ceftriaxone
• Vancomycin (coverage against resistant
  Streptococcus pneumoniae)
• If patient lt 3 months or gt 50 years
• Same as above, but also
• Add ampicillin to provide coverage of L.
  monocytogenes and S. agalactiae.

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Cellulitis
Cellulitis is an inflammation of the connective
tissue underlying the skin, that can be caused by
a bacterial infection.
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Cellulitis
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Bacterial Causes of Cellulitis

• Staphylococcus aureus 13-37
• Streptococcus pyogenes 4-17
• Other streptococci 1-18

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Treatment of Cellulitis
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Treatment of Cellulitis

• Mild Disease (oral formulations)
• Antistaphylococcal penicillins (Dicloxacillin)
• First Generation Cephalosporins (Cephalexin,
  Cefadroxil)
• Clindamycin
• Macrolides (Erythromycin, azithromycin,
  clarithromycin)

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Treatment of Cellulitis

• Severe Disease (intravenous formulations)
• Antistaphylococcal penicillins (Nafcillin,
  oxacillin)
• First-generation cephalosporins (cefazolin)
• Clindamycin

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Treatment of Cellulitis

• If MRSA is suspected
• Vancomycin
• Linezolid
• Daptomycin
• Tetracyclines (Tigecycline, doxycycline)
• Sulfa drugs (Trimethoprim-sulfamethoxazole)
• 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)

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Bacterial Causes of Acute Otitis Media

• Streptococcus pneumoniae 25-50
• Haemophilus influenzae 15-30
• Moraxella catarrhalis 3-20

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Treatment of Acute Otitis Media
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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)

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Sulfmethoxazole Used in combination with
Trimethoprim (co-trimoxazole)
Sulfisoxazole Used in combination with
Erythromycin
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Infective Endocarditis
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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.

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• 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.

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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)

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Bacterial Causes of Endocarditis

• Viridans group streptococci 18-48
• Staphylococcus aureus 22-32
• Enterococci 7-11
• Coagulase-negative staphylococci 7-11
• HACEK organisms 2-7

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Viridans Group streptococci

• Viridans streptococcus are alpha-hemolytic,
  normal flora of the oral, respiratory tract, and
  GI mucosa.

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• They are the major cause of bacterial
  endocarditis in people with damaged heart valves.
  They may enter the blood stream after dental
  procedures.

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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

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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

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• Even intensive therapy may not be sufficient, and
  surgical intervention is often required
• Despite intensive antibiotic therapy, mortality
  remains high 20-25.

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Prosthetic Valve Endocarditis

• Many cases of endocarditis are associated with
  prosthetic valves in the heart

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• 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

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Treatment of Prosthetic Valve Endocarditis

• Vancomycin Gentamicin Rifampin
• With or without cefepime or ceftriaxone

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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.

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• Diagnosis may involve
• Removal and culture of the catheter
• Growth of bacteria from blood cultures

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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

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Treatment of Intravascular Catheter-related
Infections
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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

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Intra-Abdominal Infections
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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

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Bacterial Causes of Intra-abdominal Infections

• Gram-negative bacilli
• Escherichia coli 32-61
• Enterobacter spp. 8-26
• Klebsiella spp. 6-26
• Proteus spp. 4-23

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Bacterial Causes of Intra-abdominal Infections

• Gram-positive cocci
• Enterococci 18-24
• Streptococci 6-55
• Staphylococci 6-16

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Bacterial Causes of Intra-abdominal Infections

• Anaerobic bacteria
• Bacteroides spp.
• Clostridium spp.

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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

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Treatment of Intra-Abdominal Infections

• b-Lactam/b-lactamase inhibitor combinations
  (piperacillin/tazobactam)
• Carbapenems (imipenem, meropenem)
• Aminoglycoside (gentamicin, tobramycin, amikacin)
• metronidazole
• Ciprofloxacin metronidazole

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Treatment of Intra-abdominal Infections