Pneumococcal Case

Present illness. A 35-year-old male resident of Bacolod City, presents with fever and cough. He was well
until three days earlier, when he suffered the onset of nasal stuffiness, mild sore throat, and a cough
productive of small amounts of clear sputum. Today, he decided to seek physician assistance because of
an increase in temperature to 38.3 degrees Celsius and spasms of coughing that produce purulent
secretions. On one occasion, he noted a few flecks of bright-red blood in his sputum.

Other pertinent history. It is March. He lives in a home in the city with his wife and three children, aged
7, 9, and 11 years. The children are fully immunized. The 11-year-old child is recovering from a “nagging”
cough that has persisted for 10-14 days.

The family has a pet dog who is 5 years old and appears to be well. The patient has not traveled outside
the city in the past year. He is an office manager.

Medical history. The patient has no history of familial illness, hospitalizations, or trauma. There are no
drug allergies or intolerance. The only medication he takes is paracetamol occasionally, for headaches.
He drinks beer or wine in moderation. Patient also claims he never smokes.

Physical examination. His body temperature is 38.9ºC (100ºF), his pulse is 110 beats/min and regular,
and his respiratory rate is 21 breaths/min. His oxygen saturation is 93% while breathing room air. There
is mild erythema of the mucosa of the nose and posterior oropharynx. Inspiratory “rales” are heard at
the right lung base.

Laboratory and radiographic findings. His hemoglobin level is 12.5 g/dL, with a hematocrit of 36%. His
WBC count is 13,500 cells/uL, with 82% polymorphonuclear cells, 11% band forms, and 7% lymphocytes.
His platelet count is 180,000 cells/uL. The results of multichemistry screen are unremarkable.

Chest radiography documents bilateral lower lobe infiltrates that are more pronounced on the right
side. There are no pleural effusions.

Questions:

1. What is your primary diagnosis?

The patient is febrile with tachycardia. Cough productive of mucoid, purulent, or blood-tinged
sputum suggestive of Community-Acquired Pneumonia.
2. What are your differential diagnosis?

Differential Diagnosis Most Least likely

likely
Tuberculosis Cough, blood-tinged sputum, Loss of appetite, Unintended
Fever weight loss, Night sweats

Chronic Obstructive Pulmonary Cough, Rales, Sputum Unintended weight loss,

Disease Production Cyanosis, Chest pain

Acute Bronchitis Cough, Sputum Production, Bilateral lower lobe infiltrates

Fever, Sore throat

3. What is the pathogenesis of your primary diagnosis?

Once microorganisms reach the alveolar space, they cause pneumonia by overcoming the last
defense mechanism of the lung, the alveolar macrophage. If the alveolar macrophage is unable to
control the growth of the microorganisms, then, as a final protective defense mechanism, the lungs
develop a local inflammatory response. This local inflammatory response is characterized by movement
of white blood cells, lymphocytes and monocytes from the capillaries into the alveolar space. The local
and systemic inflammatory response is responsible for the majority of the signs, symptoms, and
laboratory abnormalities that characterize the community-acquired pneumonia a (CAP) syndrome.

4. What are the virulence factors of the etiologic agent responsible for the infection?

 The polysaccharide capsule is probably the most important virulence factor of

the pneumococcus. The role of the capsule in virulence stems from its antiphagocytic activity.

 Hyaluronidase breaks down hyaluronic acid that may aid bacterial spread and colonization.

 Pili mediates binding of pneumococci to cells.

5. What other diagnostic tools would you request that would help you in your management?

 Microbiologic tests: Sputum Gram stain, Acid-fast staining and Culture and Sensitivity

 Serology: A fourfold rise in titer of specific IgM antibody can assist in the diagnosis of
pneumonia due to some pathogens; however, the time required to obtain a finalresult makes
serology of limited clinical utility.

 HIV testing

 Urine antigen tests for S. pneumoniae and Legionella pneumophila type 1 can be helpful.
  PCR of nasopharyngeal swabs for detection of a respiratory viral infection and detection of many
atypical bacteria.

 Biomarkers such as the Acute phase reactants, C-Reactive Protein and Procalcitonin

 Blood Culture if Patient progresses to severe CAP

6. What is your treatment plan?

 Initial management of CAP is relies on assessment of the patient’s severity of illness, underlying
medical conditions and risk factors as well as adherence to a treatment plan. Based on the
patient’s vital signs, presenting features during physical exam and Chest X-ray results we can
classify the patient’s CAP as Low-risk and can be treated as an outpatient case, based on CURB-
65 and Pneumonia Severity Index. Patients with Low-risk CAP can be sent home on oral
antibiotics.

 Empirical Antimicrobial Therapy for CAP without Co-Morbid Illness include:

 1 gm Amoxicillin TID or

 Extended macrolides such as Clarithromycin 500 mg PO BID or Azithromycin 500 mg PO

especially if patient has a history of beta-lactam allergy or

 Doxycyclin 100 mg PO bid

 Treatment duration for 5-7 days (3-5 days for Azalides for S. pneumonia) Patients should be
afebrile for 48 to 72 hours with no signs of clinical instability before discontinuation of
treatment.

 Fever and leukocytosis usually resolve within 2–4 days. Patients who have not responded to
therapy by day 3 should be reevaluated, with consideration of alternative diagnoses, antibiotic
resistance in the pathogen, and the possibility that the wrong drug is being given.

7. What are the probable complications that you would foresee in this patient?

Progression to severe CAP if left untreated and common complications of severe CAP include:

 respiratory failure,

 shock and multiorgan failure

 Coagulopathy

 Exacerbation of comorbid disease.

Noteworthy conditions include

 Metastatic infection

(e.g., brain abscess or endocarditis) is very unusual and will require a high degree of suspicion
and a detailed workup for proper treatment.

 Lung abscess

may occur in association with aspiration or with infection caused by a single CAP pathogen, such
as CA-MRSA, P. aeruginosa, or (rarely) S. pneumoniae. Aspiration pneumonia is typically a polymicrobial
infection involving both aerobes and anaerobes.

 Complicated Pleural effusion

A significant pleural effusion should be tapped for both diagnostic and therapeutic purposes. If
the fluid has a pH of <7, a glucose level of <2. 2 mmol/L, and a lactate dehydrogenase concentration of
>1000 U/L or if bacteria are seen or cultured, then it should be completely drained; a chest tube is often
required and video-assisted thoracoscopy may be needed for late treatment or difficult cases.

8. What are the clinical risk groups of this infection? How can this infection be prevented?

 Incidence rates of CAP are highest at the extremes of age (i.e., <4 and >60 years).

 Risk factors for CAP include alcoholism, asthma, immunosuppression, institutionalization, and an
age of ≥70 years (vs. 60–69 years).

 Many factors—e.g., tobacco smoking, chronic obstructive pulmonary disease, colonization with
methicillin-resistant S. aureus (MRSA), recent hospitalization or antibiotic therapy—influence
the types of pathogens that should be considered in the etiologic diagnosis.

Prevention:

 Pneumococcal Vaccine

 Polysaccharide (PPSV-23) and Conjugate (PCV-13)

 For elderly, immunocompetent: PCV-13 then PPSV-23 after 1 year

 For immunocompromised: PCV-13 then PPSV-23 after 8 weeks

 For those with previus PPSV: PCV-13 at least 1 year after recent dose and PPSV-23 5 years after
initial dose

Source: Philippine Society for Microbiology and Infectious Diseases: Adult Immunization
Recommendation; 2017
2015 CDC Pneumococcal Vaccine Recommendations

 Adults ≥65 years old

 Children and Adults from ages 2-64 years with Chronic Illnesses specifically with increased risk of
pneumococcal infections (Sickle cell disease, Cardiovascular and Pulmonary diseases. Diabetes,
alcoholism, cirrhosis, cochlear implants and leaks of Cerebrospinal fluid)

 Any adult aged 19 – 64 years who is a smoker or who has asthma

 Adults and Children older than aged 2 years who are immunocompromised (including HIV/AIDS,
Long-term Steroids, Hodgkin’s disease, lymphoma or leukemia, kidney failure, multiple
myeloma, nephrotic syndrome, organ transplant, damaged or no spleen, radiation or
chemotherapy)

 Residents of Nursing homes or long-term care facilities.

Because of an increased risk of pneumococcal infection, even among patients without

obstructive lung disease, smokers should be strongly encouraged to stop smoking.

Staphylococcal Case

A 26year old female was well until 2 days prior to admission when she had a fever to 39.9ºC and
vomiting. On the morning of admission, she had loose stools, continued fever, and vomiting. She was
seen by her attending doctor who noted that she was hypotensive (BP 76/48 mmHg) with a heart rate of
120 beats/min and a temperature of 38ºC . She had an erythematous rash , which was most prominent
on her trunk. Cultures were obtained. The patient was given intravenous fluids and IV antibiotics and
transported to the hospital, where she was admitted into the Adult Intensive Care Unit.

Laboratory studies indicated elevated liver enzymes, increased creatinine and blood urea
nitrogen, and WBC count of 14,100 mm3 with 78% neutrophils and 18% band forms. The patient had
begun her menstrual period 4 days before she became ill.

1. Does this patient have infection?

● Yes

Is it bacterial or viral?

● Bacterial

What evidence do you have?

● Based on question number 7, the vaginal culture results presented positive for many catalase
positive, gram positive cocci.

● IV antiobiotics were given to the patient before being transferred to the hospital. If this case
was viral infection, the attending doctor would not have given antibiotics.

● A high WBC count with predominant neutrophils and band forms may also indicate bacterial

infection.

2. What are the potential sites for infection in this patient as judged from the clinical story?

The possible sites for infection would include the vagina, liver and kidneys. This is reflected in
the patient’s lab results showing elevated liver enzymes, creatinine and BUN. Also, the

patient had begun menstruation 4 days prior to being ill.

3. What additional history would you like to have?

● If the patient used vaginal tampons

● If the patient is married and is using contraceptives

How can infection be linked to her periods?

● TSS is associated with 5 days post onset of menses in women with tampons or with staph
wound infections.

4. What is your primary diagnosis by this time?

Toxic Shock Syndrome (TSS)

What is the case definition of this syndrome and correlate it with your patient’s presentation?

Abrupt onset of fever, vomiting, diarrhea, erythematous rash, hypotension (76/48 mmHg).

5. What type of infections (etiologic agents) can lead to this syndrome?

Staphylococci

6. What cultures would you consider obtaining from this patient?

Vaginal, Blood agar plate

7. The vaginal culture was positive for many catalase positive, Gram positive cocci. What organism do
you expect this to be?

Staphylococcus aureus

What is the normal flora of the vagina?

The normal vaginal flora consist mainly of lactobacilli, which produces lactic acid to protect
against infection by pathogenic species. Others include Atopobium, Leptotrichia, Leuconostoc,
Megasphaera, Pediococcus, Streptococcus and Weissella. Some bacterial species that are frequently
found in the vagina such as gram positive cocci: Atopobium vaginae, Peptostreptococcus spp.,
Staphylococcus spp;, Streptococcus spp., Mobiluncus, Prevotella spp., and Gram-negative enteric
organisms, such as Escherichia coli.

Since the vaginal isolate is one of the normal flora of vagina how can you attribute significance to the
culture results?

The culture results are indicative that there was an increase in the amount of catalase positive,
Gram-positive cocci, which can be interpreted as intoxication due to an increase in the amount of toxins
produced by Staphyloccus spp. leading to the conclusion of the primary diagnosis which is toxic shock
syndrome.

8. What virulence factor does this organism produce which is believed to be responsible for the signs
and symptoms in this patient?

 In toxic shock syndrome, staphylococcal infections produce an exotoxin (TSST-1) that causes the
fever and rash as well as enterotoxins.

What is the pathophysiology of this syndrome?

 Vaginal colonization of Staphylococcus aureus → exotoxin production → immune response

(exotoxins act as superantigens) → shock and tissue injury (IL-1: high fevers, myalgia; TNF:
hypotension, edema; IL-2 and IFN-gamma: rash)

How do these toxins lead to the clinical manifestations?

 Enterotoxin B – diarrhea and vomiting

Acts on the neural receptors in the gut → CNS stimulation → vomiting

 Toxic shock syndrome toxin (TSST-1, TSST-2)

Binds to MHC class II antigen → T-cell stimulation → fever, shock, multisystem involvement,
desquamative rash

9. What is your therapeutic strategy?

Nafcillin or Oxacillin 2g q4H

Vancomycin – for penicillin-allergic patients

10. What are the other illnesses caused by this organism?

9. What is your therapeutic strategy?

Nafcillin or Oxacillin 2g q4H

 Vancomycin – for penicillin-allergic patients

10. What are the other illnesses caused by this organism?

Skin infections Pimples

Impetigo
Boils
Cellulitis
Folliculitis
Carbuncle
Skalded skin syndrome
Abscesses

Life threatening Pneumonia

Meningitis
Osteomyelitis
Endocarditis
TSS or Toxic Shock Syndrome
Bacteremia
Sepsis

Streptococcal Case

A 19 year old female awakened with pain and swelling in the right ankle. Four weeks ago she
had a febrile illness with a sore throat and headache and was treated with amoxicillin. On admission, she
had a warm, swollen right ankle and a new systolic heart murmur thought to be consistent with mitral
regurgitation.

Questions:

1. The patient previously had a sore throat and although we do not have culture results from that
illness, what pathogen would likely have grown from her throat culture?

The pathogen most likely for the sore throat developing would be Streptococcus pyogenes
(GAS).

2. What is the relationship between her pharyngitis and the subsequent development of joint
problem? What is your diagnosis and why?

Polyarthritis is the major musculoskeletal manifestation. The arthritis is typically migratory and
involves the following large joints: elbows, wrists, knees, and ankles. Joint involvement may range from
general arthralgia to a painful, inflammatory arthritis, abnormal host immune response to some
component of the group A Streptococcus is responsible. The M protein of GAS shares certain amino acid
sequences with some human tissues, and this has been proposed as a source of cross-reactivity between
the organism and human host that could lead to an immunopathologic immune response.
3. What is the criteria for this infection? Did the patient fulfill the said criteria?

4. What hemolysins does this organism produce which help to identify infection with this organism?

Streptococcus pyogenes elaborates 2 distinct hemolysins. Streptolysin O is toxic to a wide variety

of cell types, including myocardium, and is highly immunogenic. Streptolysin S is another virulence
factor capable of damaging polymorphonuclear leukocytes and subcellular organelles but is non
immunogenic.

5. In the absence of positive culture what other evidence or laboratory test can you seek for recent
prior infection?

We can utilize the ASO TITER test. The determination of the antibody responses to this protein
(antistreptolysin O [ASO] titer) is often useful in the serodiagnosis of recent infection If culture is not
possible. Or swabbing the throat and testing for GAS by rapid antigen detection test (RADT) and/or
microbiology culture is recommended to establish a diagnosis of GAS pharyngitis because even patients
who present with all of the typical features of streptococcal pharyngitis are found to have GAS only 30%
to 50% of the time.

6. What is the pathogenesis of this infection?

Streptococcal pharyngitis results from the proliferation of GAS in the pharynx. GAS has several
surface proteins and produces numerous extracellular products that facilitate infiltration and
subsequent evasion of the immune system. The M protein is responsible for its virulence and clinical
complications.

7. What are the other virulence factors of this infection’s etiologic agent?

Other virulence factors could also include: pyrogenic exotoxins and other nucleases.
  Pyrogenic exotoxins (SPEs) includes SPEs A, B, C, and F. These toxins are responsible for
the rash of scarlet fever, and others such as pyrogenicity, cytotoxicity, and enhancement
of susceptibility to endotoxin. SPE B is a precursor of a cysteine protease, another
determinant of virulence.

 Nucleases assist in the liquefaction of pus and help to generate substrate for growth.

Other extracellular products include:

 NADase (leukotoxic), hyaluronidase (which digests host connective tissue, hyaluronic

acid, and the organism's own capsule), streptokinases (proteolytic), and streptodornase
A-D (deoxyribonuclease activity).

8. How would you treat the patient’s current condition?

9. What is the classification of this organism and the associated typical infection/s? (Table)

10. Give the treatment options of Group A Streptococcal infections (Table). Give the treatment of
Asymptomatic Pharyngeal Colonization with GAS.