Pneumococcal Infections Workup
- Author: Claudia Antonieta Nieves Prado, MD; Chief Editor: John L Brusch, MD, FACP more...
If a pneumococcal infection is suspected or considered, Gram stain and culture of appropriate specimens should be obtained, when possible. Potential specimens may include one or more of the following:
Cerebrospinal fluid (CSF)
Pleural fluid or lung aspirate
Other abscess or tissue specimens
Specimens should be obtained prior to the initiation of antibiotic therapy and inoculated directly into blood-culture bottles, when possible.
Antibiotic susceptibilities should be obtained routinely on all cultures with growth of S pneumoniae. Note that MIC breakpoints are different depending on the specimen type.
Other laboratory values that may be helpful in diagnosis and treatment include a complete blood cell (CBC) count and differential, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP).
In children who do not produce sputum and in adults with a nonproductive cough, the diagnosis may be made based on urine antigen testing for S pneumoniae. As with urinary antigen testing for Legionella, antigenuria may not be present in early infection or in patients without bacteremia, but, if present, may persist after clinical resolution of infection. The pneumococcal urinary antigen assay may augment the standard diagnostic methods of blood culture and sputum culture, as it provides rapid results. It is unable to provide antimicrobial susceptibility data, so it does not supplant traditional culture methods.
Conjunctivitis, otitis media, sinusitis
Laboratory work is not usually obtained in patients with conjunctivitis, otitis media, or sinusitis unless they have unusually high fevers or have an extremely ill appearance. If specimens are obtained, they should be sent for Gram stain and culture and susceptibility. In these cases, isolation of S pneumoniae should be considered a strong indication for pathogenicity and treatment.
Many patients with pneumonia are treated empirically. Antibiotics used in these cases should include those that cover S pneumoniae. In severe, unusual, or complicated cases or those that require hospitalization, an attempt to obtain sputum cultures should be made. An acceptable sputum sample is indicated by the presence of few epithelial cells and many polymorphonuclear neutrophils (a ratio of 1:10-20). The presence of many gram-positive cocci in pairs and chains on Gram stain of sputum provides good evidence for pneumococcus. When large effusions/empyema is present, pleural fluid should be obtained for Gram stain and culture.
The yield of blood cultures in pneumonia is relatively low. The most common bacteria isolated is S pneumoniae. Blood cultures are not indicated in all hospitalized patients with CAP, but they should be obtained in patients with severe pneumonia, immunocompromise (alcohol abuse, leukopenic, liver disease, asplenia, HIV infection), and in outpatient therapy failure.
Most patients with pneumococcal pneumonia have significant leukocytosis (>12,000 cells/μL), and up to one fourth have a hemoglobin level of 10 mg/dL or less.
A small study by Casado Flores et al evaluated a rapid immunochromatographic test for detection of the pneumococcal antigen, C polysaccharide antigen, in children with pleural effusion. The positive predictive value was 96%, and the sensitivity and specificity were high. In this study, the immunochromatographic test made identification of the pneumococcal origin of effusion easy.
In most patients with invasive pneumococcal infections, the WBC count is elevated (>12,000 cells/μL) and there is a predominance of neutrophils. However, the WBC count may be normal, especially early in the disease process. Conversely, leukopenia may indicate severe disease and is a poor prognostic sign. The ESR and CRP level are typically elevated.
The development of polymerase chain reaction (PCR) assays for S pneumoniae with sufficient sensitivity and specificity is being widely investigated. Successful commercial assays may prove to be clinically useful but are not yet commercially available.
CSF findings are typical of those found in bacterial meningitis and usually include the following:
Elevated opening pressure (>20 cm H 2O)
Elevated WBC count (1000-5000 cells/μL) with neutrophilic predominance (>80%)
Elevated protein level (>100 mg/dL)
Decreased glucose level (< 40 mg/dL; <60% of simultaneous blood glucose)
Highly elevated lactic acid levels (>6 mmol/L)
Most patients with pneumococcal meningitis who do not receive antibiotics in the 4-6 hours prior to lumbar puncture will have positive results on Gram stain and/or culture.
Rapid antigen tests (eg, latex agglutination or enzyme immunosorbent assays) can be performed on CSF (as well as sputum and urine) but rarely provide information beyond what is obtained with Gram stain and culture unless antibiotics were administered to the patient prior to performing the lumbar puncture.
Blood culture results are positive in up to 90% of patients.
The WBC count may be elevated, and blood cultures are positive for growth of S pneumoniae.
Other invasive infections
The WBC count, neutrophil level, CRP level, and ESR are often elevated in patients with bone, joint, soft tissue, cardiac, and other invasive infections. Specimens of appropriate material may yield positive Gram stain findings and/or culture growth. Blood cultures are frequently positive and should be obtained when possible. In females with peritonitis, vaginal swab cultures should be obtained in addition to blood and peritoneal cultures.
Culture and Susceptibility
Antimicrobial susceptibility testing should be performed on all isolates of S pneumoniae, regardless of the isolation site, because of the increasing prevalence of intermediately susceptible and resistant isolates. All isolates should be tested for susceptibility to penicillin and either cefotaxime or ceftriaxone. In addition, CSF isolates should be tested for susceptibility to vancomycin and meropenem. CSF isolates that are found to be nonsusceptible to penicillin should also be tested for susceptibility to rifampin.
Microbiology laboratories should follow established guidelines regarding inoculum size and media (Mueller-Hinton agar with sheep, horse, or lysed horse red blood cells). Isolates from patients with invasive disease should undergo testing with quantitative minimal inhibitory concentration (MIC) techniques (eg, broth microdilution, antibiotic gradient strips).
The Clinical and Laboratory Institute (CLSI) (2010) has defined S pneumoniae susceptibility as follows[1, 2] :
Pneumonia: For penicillin-sensitive S pneumoniae (MIC <2 μg/mL), penicillin G or amoxicillin is considered first-line therapy. For penicillin-resistant S pneumoniae (MIC ≥2 μg/mL), the choice of antimicrobial agent should be directed by susceptibility testing.
Cefotaxime or ceftriaxone considerations are as follows:
- Susceptible (non-CNS/CNS): MIC is ≤1/0.5 µg/mL, respectively.
- Intermediate (non-CNS/CNS): MIC is 2/1 µg/mL, respectively.
- Resistant (non-CNS/CNS): MIC is ≥4/2 µg/mL, respectively.
Strains with intermediate or resistant susceptibility patterns should be considered nonsusceptible and alternate therapy used.
Chest radiography should be performed in most patients with evidence of invasive pneumococcal infection and in those with pneumococcal pneumonia. The typical chest radiography finding in adolescents and adults with pneumococcal pneumonia is lobar consolidation. Infants and young children with pneumococcal pneumonia more often have a pattern of scattered parenchymal consolidation and bronchopneumonia. Other chest radiography findings may include air bronchograms, pleural effusions/empyema, pneumatoceles, and, rarely, abscesses. Cavitation is not a feature of S pneumoniae pneumonia and, if present, should prompt investigation for other pathogens.
Chest ultrasonography or chest CT scanning may be obtained to provide information on the presence and/or extent of pleural effusion/empyema and parenchymal disease. Studies investigating the diagnostic utility of lung ultrasonography to diagnose pneumonia have also been promising.
Sinus CT scanning may provide information about the presence and extent of sinus disease. Positive findings include opacification or air-fluid levels.
Facial CT scanning should be obtained in patients with periorbital or orbital cellulitis to look for evidence of soft tissue swelling, bony involvement, cranial nerve impingement, or proptosis.
MRI or CT scanning of affected bones or joints should be obtained to evaluate for evidence of joint destruction, periosteal elevation, or a mass.
An MRI of the brain may be obtained in patients with meningitis to determine the location and extent of involvement but is not required by Infectious Disease Society of America (IDSA) guidelines.
Echocardiography should be performed in patients in whom endocarditis is suspected.
See the list below:
Middle ear fluid aspiration
Pleural fluid aspiration
Chest tube thoracostomy or catheter placement
Video-assisted thoracoscopy (VATS) or pleural decortication
Joint fluid aspiration and/or wash-out of joint space
Soft tissue/muscle biopsy
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Flamm RK, Sader HS, Farrell DJ, Jones RN. Antimicrobial activity of ceftaroline tested against drug-resistant subsets of Streptococcus pneumoniae from U.S. medical centers. Antimicrob Agents Chemother. 2014. 58 (4):2468-71. [Medline]. [Full Text].
- Table 1. Routine Vaccination With Pneumococcal Vaccines[84, 85, 82]
- Table 2. Vaccination of High-Risk Children Aged 2-18 Years With Pneumococcal Polyvalent Vaccine 23-Valent
- Table 3. Vaccination of High-Risk Adults Aged 19 Years or Older With Pneumococcal Vaccines
- Table 4. Recommended Schedule for Doses of PCV13, Including Catch-up Immunizations in Previously Unimmunized and Partially Immunized Children
|Children aged 6 weeks through 5 years: 0.5 mL IM; series of 4 doses at ages 2, 4, 6, and 12-15 months (catch-up schedule through age 5 y)||Pneumococcal conjugate vaccine 13-valent (Prevnar 13)|
|Adults ≥50 years*: 0.5 mL IM as a single dose||Pneumococcal conjugate vaccine 13-valent (Prevnar 13, PCV13)|
|Adults >65 years*†: 0.5 mL IM||Pneumococcal polyvalent vaccine 23-valent (PPSV23); 6-12 mo after PCV13|
|*Although PCV13 is licensed by the FDA for individuals aged ≥50 y, ACIP recommends routine vaccination with both PCV13 plus PPSV23 for individuals aged ≥65 y.
†Those who received PPSV23 before age 65 years for any indication should receive another dose of the vaccine at age 65 years or later if at least 5 years have passed since their previous dose.
|Pediatric Risk Group||Condition|
|Immunocompetent||Chronic heart disease (particularly cyanotic congenital heart disease and cardiac failure)
Chronic lung disease (including asthma if treated with high-dose corticosteroids)
Cerebrospinal fluid leaks
|Functional or anatomic asplenia||Sickle cell disease and other hemoglobinopathies
Congenital or acquired asplenia or splenic dysfunction
|Immunocompromising conditions||HIV infection
Chronic renal failure and nephrotic syndrome
Immunosuppressive drugs or radiation therapy, malignant neoplasms, leukemias, lymphomas, Hodgkin disease, solid organ transplantation
|Risk Group||Condition||PCV13||PPSV23||Revaccinate With PPSV23 5 Years After First Dose|
|Immunocompetent individuals||Chronic heart disease*|
|Chronic lung disease†|
|Cerebrospinal fluid leaks||x||x|
|Chronic liver disease, cirrhosis||x|
|Functional or anatomic asplenia||Sickle cell disease and other hemoglobinopathies||x||x||x|
|Congenital or acquired asplenia||x||x||x|
|Immunocompromised individuals||Congenital or acquired immunodeficiency||x||x||x|
|Chronic renal failure||x||x||x|
|Solid organ transplant||x||x||x|
|*Congestive heart failure and cardiomyopathies, excluding hypertension.
†Including chronic obstructive pulmonary disease, emphysema, and asthma.
‡Diseases requiring treatment with immunosuppressive drugs, including long-term systemic corticosteroids and radiation therapy.
|Age at Examination (mo)||Immunization History||Recommended Regimen*|
|2-6||0 doses||3 doses, 2 mo apart; fourth dose at age 12-15 mo|
|1 dose||2 doses, 2 mo apart; fourth dose at age 12-15 mo|
|2 doses||1 dose, 2 mo after the most recent dose; fourth dose at age 12-15 mo|
|7-11||0 doses||2 doses, 2 mo apart; third dose at age 12 mo|
|1 or 2 doses before age 7 mo||1 dose at age 7-11 mo, with another dose at age 12-15 mo (≥2 mo later)|
|12-23||0 doses||2 doses, ≥2 mo apart|
|1 dose at < 12 mo||2 doses, ≥2 mo apart|
|1 dose at ≥12 mo||1 dose, ≥2 mo after the most recent dose|
|2 or 3 doses at < 12 mo||1 dose, ≥2 mo after the most recent dose|
|Any incomplete schedule||1 dose, ≥2 mo after the most recent dose†|
|Children at high
risk‡ (24-71 mo)
|Any incomplete schedule of < 3 doses||2 doses, one ≥2 mo after the most recent dose and another dose ≥2 mo later|
|Any incomplete schedule of 3 doses||1 dose, ≥2 mo after the most recent dose|
|*In children immunized before age 12 mo, the minimum interval between doses is 4 weeks. Doses administered at age 12 months or later should be administered at least 8 weeks apart.
† Providers should administer a single dose to all healthy children aged 24-59 mo with any incomplete schedule.
‡Children with sickle cell disease, asplenia, chronic heart or lung disease, diabetes mellitus, CSF leak, cochlear implant, HIV infection, or another immunocompromising condition. PPV23 is also indicated (see below).