eMedicine - Pneumococcal Infections : Article by Christian P Sinave, MD, FRCPC

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Pneumococcal Infections

Last Updated: March 18, 2004

Synonyms and related keywords: Streptococcus pneumoniae, S pneumoniae, pneumococcus, pneumococci, upper respiratory tract disease, lower respiratory tract disease, upper respiratory disease, lower respiratory disease, respiratory disease, community-acquired pneumonia, CAP, pneumonia, lung infection, respiratory infection, pneumococcal disease, otitis media, pharyngeal infection, nosocomial pneumonia, hospital-acquired pneumonia, hospital acquired pneumonia, community acquired pneumonia, bronchopneumonia, broncho-pneumonia, meningitis, tracheobronchitis, acute sinusitis, sinusitis, pneumococcal sepsis

AUTHOR INFORMATION Section 1 of 11

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Author: Christian P Sinave, MD, FRCPC, Associate Professor, Department of Medical Microbiology and Infectious Diseases, University of Sherbrooke, Canada

Christian P Sinave, MD, FRCPC, is a member of the following medical societies: American Society for Microbiology, and Canadian Infectious Disease Society

Editor(s): Thomas Herchline, MD, Associate Professor, Department of Internal Medicine, Division of Infectious Disease, Wright State University; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Aaron Glatt, MD, Chief Medical Officer, Professor of Clinical Medicine New York Medical College, Medicine and Infectious Diseases, New island Hospital; Eleftherios Mylonakis, MD, PhD, Assistant Professor of Medicine, Harvard Medical School, Assistant in Medicine, Division of Infectious Disease, Massachusetts General Hospital; and Burke A Cunha, MD, MACP, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital

Disclosure

INTRODUCTION

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Background: Worldwide, pneumococcus is a significant cause of illness, hospitalization, and death. It causes upper and lower respiratory diseases and more invasive infections.

Despite appropriate antimicrobial therapy, pneumococcal infections remain associated with significant mortality. Austrian and Gold compared data from the preantibiotic and postantibiotic eras and demonstrated similar mortality rates during the first few days of the disease in patients with bacteremic pneumonia.

Pathophysiology: Streptococcus pneumoniae produces few toxins. It causes diseases by its capacity to replicate in host tissues. The presence of a capsule allows an escape from phagocytosis, resulting in an intense inflammatory response in hosts who are immunologically naive. Colonization of the oropharynx by bacterial adherence to human pharyngeal cells is the usual first step.

The alternative pathway of the complement is first activated. Anticapsular antibodies are effective in providing protection against pneumococcal infection. They appear 5-8 days after the onset of infection. By this time, fever usually disappears in the absence of treatment. Natural immunity follows infections as well as colonization. Studies on the prevalence of measurable levels of antibody in the US suggest that the adult population is susceptible to most S pneumoniae that commonly cause infection.

Frequency:

In the US: Among adults with community-acquired pneumonia (CAP) requiring hospital admission, S pneumoniae ranks first as a cause and accounts for most of such cases.
Pneumococcal disease is estimated to account for 3,000 cases of meningitis, 50,000 cases of bacteremia, 500,000 cases of pneumonia, and 7 million cases of otitis media each year.
The pharyngeal colonization rate is 5-10% of healthy adults and 20-40% of healthy children. The colonization rate is highest during mid winter.

Internationally: In Canada, population-based surveillance studies for invasive pneumococcal disease revealed an overall incidence between 11.8-16.1 cases per 100,000 persons between 1995-1997.
In the United Kingdom, pneumococcus is responsible for 30-50% of community and 8% of nosocomial pneumonia, and it may be the cause of most cases of pneumonia with no identified causative organism.
In the developing world, the attack rate of pneumococcal disease is high, particularly in children. It is estimated to cause 60-90% of lower respiratory tract infections in Gambian children younger than 5 years and as many as 100 cases per 1000 population in adult South Africans living in crowded mining communities.
In children living in the developing world, the incidence of invasive pneumococcal disease is several times higher than the incidence in industrialized countries.

Mortality/Morbidity:

Mortality varies widely among age groups and diseases. It is very high with overwhelming postsplenectomy infection. It is also higher in patients who are debilitated and immunocompromised.

Mortality from meningitis varies, with multiple predictive factors. It can be as high as 35% in adults older than 60 years. In developing countries, children younger than 2 years have the highest mortality rate.

In a meta-analysis on 4432 patients, the mortality of CAP was reported to be 12.3%.

Race:

Any racial difference in prevalence probably is due to socioeconomic factors.

Genetic factors may play a role. Sickle cell disease and infection with human immunodeficiency virus (HIV) predispose the person to invasive infections, particularly in children.

Sex: No sexual predilection exists.

Age:

Young children and elderly adults are particularly prone to infections with S pneumoniae.

With the exception of sinusitis, pneumococci rarely infect healthy adults and teenagers. The occurrence of such infections in that population should prompt investigation for predisposing factors like HIV infection or other immunodeficiencies.

CLINICAL

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History: A broad spectrum of diseases are caused by S pneumoniae.

Upper respiratory infections
- Sinusitis
- Acute otitis media
- Tracheobronchitis

Lower respiratory infections
- Broncho-pneumonia
- Pneumonia, with or without bacteremia or empyema

Invasive infections
- Primary bacteremia in children
- Meningitis
- Spontaneous bacterial peritonitis
- Sepsis with tissue seeding (septic arthritis, myositis, pericarditis, osteomyelitis, endocarditis)

Otitis media and acute sinusitis - Main causes are infection with pneumococci species and Haemophilus influenzae
Pneumonia

The absence of predisposing factors is rare in pneumococcal pneumonia affecting older children, teenagers, and adults younger than 60 years.
Cough, sputum production, and fever are typical of acute pyogenic pneumonia.
Nonspecific symptoms (mainly in children) can include abdominal pain, vomiting, and irritability.
Patients with chronic obstructive pulmonary disease may present with an increased daily production of sputum, changes in color (yellow-green), and ticker sputum.
Patients with viral respiratory infection may develop pneumococcal infections and have acute deterioration with high fever and cough.

Meningitis

No distinctive clinical features exist for pneumococcal meningitis (compared to other etiologies).
Rapid progression of headache and fever occur, occasionally following respiratory tract symptoms.
Petechial rash may mimic Neisseria meningitidis.
Progressive cerebral dysfunction occurs.

Primary bacteremia

This condition is more frequent in children than in adults.
A 6-year study of childhood (<18 y) pneumococcal bacteremia at a US community hospital identified 122 patients, with incidences as follows:
- Approximately 68% were younger than 2 years, and only 10% were older than 5 years.
- Approximately 30% had primary bacteremia (no focal source of bacteremia).
- The causes of secondary bacteremia in the remainder were meningitis (11.5%), pneumonia (37%), and acute otitis media (30%). There were 14 children with multiple sources of bacteremia.

Spontaneous bacterial peritonitis

S pneumoniae is a cause of primary peritonitis in adult patients who are cirrhotic.
In children with nephrotic syndrome, pneumococci and group A streptococci were the main bacterial causes of peritonitis. However, Enterobacteriaceae species have become a more prevalent cause in the past 3 decades.

Postsplenectomy sepsis

It also is called overwhelming postsplenectomy sepsis.
S pneumoniae is involved in 50-90% of cases.
The highest risk is related to splenectomy for Hodgkin disease and thalassemia. The lowest risk is for trauma, and all other indications for splenectomy are classified as intermediate risk.
More than 80% of cases occur within the first 2 years after splenectomy.
Clinical presentation includes an abrupt onset, fulminant sepsis with disseminated intravascular coagulation, gangrenous extremities, shock, seizures, and death despite appropriate therapy.

Other infections

They usually result from tissues seeding during bacteremia.

Endocarditis is rare, causes rapid destruction of heart valves, and is seen primarily in people who are alcoholics.

Purulent pericarditis, with or without associated endocarditis, also is very rare.

Bone and joint infections may include prosthetic or natural joint septic arthritis, occasionally as a complication of rheumatoid arthritis.

Myositis and brain and epidural abscesses occasionally have been reported.

Physical:

Pneumonia

Apprehension, high fever (no or low-grade fever in older individuals) or hypothermia, and tachycardia

Hypoxia and respiratory distress, including tachypnea and splinting

Signs of pulmonary consolidation (ie, dullness to percussion, tubular breath sounds, and egophony)

Crackling sounds

Signs of pleural empyema/effusion, occasionally present (eg, flatness to percussion, decreased breath sounds)

Diaphragmatic motion (may be undetectable)

Meningitis

Bacteremia

Cerebral dysfunction - Confusion, delirium, lethargy, and coma

Meningismus - Neck stiffness and positive Kernig and Brudzinski signs

Occasional cranial nerve palsies - III, IV, VI, and VII, focal neurologic deficit, papilledema, and seizures

A petechial rash similar to meningococcemia may occur in patients who are splenectomized with overwhelming sepsis.

Indolent presentation in elderly patients who are debilitated may include lethargy, obtundation, or coma.

Otitis media and sinusitis: No specific clinical features exist for these infections when they are caused by S pneumoniae.

Overwhelming postsplenectomy signs

Fulminant course

Septic complications may include septic shock, disseminated intravascular coagulation, purpura, adult respiratory distress syndrome, acute tubular necrosis, and/or multiple organ failure.

Does not occur in normal hosts

Other infections: These may show similar physical findings for conditions caused by other bacterial pathogens

Causes: S pneumoniae is an encapsulated, gram-positive coccus identified in the microbiology laboratory by 3 reactions: catalase negativity, alpha-hemolysis, and bile solubility or susceptibility to Optochin.

Conditions that predispose the patient to pneumococcal infection

Defective antibody formation - Agammaglobulinemia and hypogammaglobulinemia, multiple myeloma, chronic lymphocytic leukemia, lymphoma, and HIV infection

Defective complement (C1 to C4)

Defective splenic function

Asplenia and splenectomy

Chronic diseases - Chronic obstructive pulmonary disease, cirrhosis of the liver, and alcoholism

Acute viral respiratory infections – Post–influenza virus

Pneumonia: The absence of predisposing factors is rare in pneumococcal pneumonia affecting elderly children, teenagers, and adults younger than 60 years.

Meningitis: Predisposing factors include head trauma, cerebrospinal fluid leak, and respiratory tract infection.

DIFFERENTIALS

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Atelectasis
Bronchitis
Empyema, Pleuropulmonary
Influenza
Klebsiella Infections
[Legionellosis]

Lung Abscess
Meningitis
Meningococcal Infections
Meningococcemia
Pericardial Effusion
Pericarditis, Acute
Pleural Effusion
Pulmonary Embolism
Sepsis, Bacterial
Septic Shock
Sinusitis, Acute

Other Problems to be Considered:

Nongonococcal infectious arthritis

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Introduction
Clinical
Differentials
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Related Articles

Atelectasis

Bronchitis

Empyema, Pleuropulmonary

Influenza

Klebsiella Infections

[Legionellosis]

Lung Abscess

Meningitis

Meningococcal Infections

Meningococcemia

Pericardial Effusion

Pericarditis, Acute

Pleural Effusion

Pulmonary Embolism

Sepsis, Bacterial

Septic Shock

Sinusitis, Acute

Patient Education

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WORKUP

Section 5 of 11

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Lab Studies:

Gram stain and culture is indicated on (1) sputum, (2) cerebrospinal fluid (CSF), (3) pleural fluid, (4) joint fluid, (5) abscess fluid, (6) bone, and (7) other biopsy specimens as follows:

Sputum, endotracheal secretions, and bronchoalveolar lavage

Always attempt to obtain a sputum sample from patients with CAP.
When a patient cannot provide an expectorated specimen, a trial of hypertonic saline mist may be helpful. If clinically indicated, another option is a bronchoalveolar lavage through flexible bronchoscopy.
Good-quality sputum (microscopic demonstration of large amount of polymorphonuclear neutrophils and few epithelial cell) showing slightly elongated gram-positive cocci in pairs is good evidence for pneumococcal pneumonia.
For sputum culture, the specimen is plated on blood containing agar and incubated under 5-10% carbon dioxide atmosphere.
Gray colonies with alpha-hemolysis are visible after 24 hours of incubation.

Sensitivity to the Optochin disk (P disk) or bile solubility confirms that the colonies are S pneumoniae and not viridans streptococci.

An absence of pathogens occasionally is reported in this setting because S pneumoniae can be overgrown by mouth flora or may be due to rapid autolysis.

Cerebrospinal fluid examination demonstrates findings typical of acute bacterial meningitis as follows:

Increased opening pressure (<180 mm of H₂O)

High white blood cell count, usually 1000-5000/mL with a predominance of neutrophils (>80%)

High protein (>100 mg/dL)

Decreased glucose (<40 mg/dL, <50% of blood glucose)

Positive Gram stain (90% of cases)

Positive culture (90%)

Pneumococcal antigen detection (sensitivity of 69-100%)

A Gram stain on a buffy coat or blood smear frequently is positive in cases of overwhelming pneumococcal sepsis and should be done for rapid diagnosis of this infection.

Pneumococcal antigen detection assay

Antimicrobial susceptibility test

During the past 2 decades, pneumococci have increasingly become less sensitive to penicillin and other antibiotics. Strains that are less susceptible to penicillin remain susceptible to nearly all other relevant antimicrobial agents.
The National Committee for Clinical Laboratory Standards (NCCLS) defined S pneumoniae susceptibility as follows:
- Susceptible when minimal inhibitory concentration (MIC) is less than 0.1 mg/mL
- Intermediate susceptibility when MIC is 0.1-1 mg/mL
- Resistant when MIC is greater than 1 mg/mL
Test pneumococci isolates with the oxacillin disk. This procedure has a positive predictive value of 100% for penicillin sensitivity if the zone of growth inhibition is 20 mm or more.
Report strains with zones of less than or equal to 19 mm as presumptively not susceptible to penicillin. Report final susceptibility after a confirmatory MIC determination. Absence of inhibition around the oxacillin disk always predicts penicillin nonsusceptibility.

Except for with minor infections, such as sinusitis and otitis media, the general laboratory tests usually ordered are as follows:
CBC count
- Leukocytosis (>12,000/mL)
- WBC count (occasionally within reference range early in disease)
- Leukopenia (<6000/mL) - Associated with overwhelming infection and a poor prognosis

Blood cultures - 2 sets
- Positive for gram-positive cocci in pairs, with later identification as S pneumoniae
- Many pneumococcal infections are associated with bacteremia, specifically, as many as one third of pneumonia cases, most meningitis cases, and all cases of postsplenectomy sepsis.

Imaging Studies:

Chest radiograph

This study is always indicated because the portal of entry of pneumococci is the respiratory tract, and any infection can be associated with pneumonia.

Very early in the disease, a patient with acute pneumonia may have a normal radiograph.

Findings can include lobar or multilobar consolidation, segmental infiltration, patchy infiltrates representing bronchopneumonia, and pleural effusion, uncommonly.

Cavitation is not a feature of pneumococcal pneumonia.

Sinus radiograph may show radiological signs of sinusitis, the most convincing being an air-fluid level in at least 1 of the sinuses.

CT scanning or magnetic resonance imaging occasionally is useful for additional lung detail.

Procedures:

Diagnostic lumbar puncture

Diagnostic pleural fluid aspiration

Chest tube thoracostomy for empyema

Percutaneous catheter placement into pleural space, usually performed under CT guidance

Needle aspiration of a joint in patients with septic arthritis

Bone and other tissue biopsies

TREATMENT

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Medical Care:

Pneumonia

S pneumoniae is the major cause of CAP.
The severity of CAP depends on host factors and can vary widely. Some patients should be admitted to intensive care units, while others can be safely treated on an ambulatory base.

Prognostic factors: Reviewing data from 14,199 patients with CAP, Fine et al classified patients in 5 risk classes with respect to risk of death within 30 days. Points were assigned according to the patient's characteristics as follows:
- Age - Points given for each year of age, with a substraction of 10 points for women; patients older than 50 years (excluded from class I)
- Coexisting conditions - Neoplastic disease (+30 points), liver disease (+20), congestive heart failure (+10), cerebrovascular diseases (+10), renal disease (+10)
- Physical examination - Altered mental status (+20), pulse 125 beats per minute or more (+20), respiratory rate of 30 breaths per minute or more (+20), systolic blood pressure of less than 90 mm Hg (+20), temperature less than 35°C or greater than 40&%176;C (+15)
- Laboratory and radiographic findings - Arterial pH less than 7.35 (+30), BUN of 30 mg/dL (11 mmol/L) or more (+20), sodium less than 130 mmol/L (+20), glucose of 250 mg/dL (14 mmol/L) or more (+10), hematocrit less than 30% (+10), partial pressure of oxygen (PO2) less than 60 mm Hg (+10), and pleural effusion (+10)
- Classes I and II are 70 points or less; class III is 71-90 points; class IV is 91-130 points; and class V is greater than 130 points.
- Mortality rates - Classes I, II, and III are less than 1%; class IV is 9.3%; and class V is 27%.
- Mortality was similar in the first 3 classes, regardless of whether patients were treated as inpatients or outpatients.
- Although subsequent hospital admission may be required, patients in class I (admission rate of 5.1%), class II (admission rate of 8.2%), and possibly class III (admission rate of 16.7%) can be treated as outpatients if follow-up can be arranged.

Tracheobronchitis: Ambulatory treatment usually is acceptable unless respiratory failure occurs. This can be a concern if the patient has severe chronic obstructive pulmonary disease.

Acute sinusitis and otitis media: With few exceptions, treat such diseases on an outpatient basis.

Septicemia, overwhelming pneumococcal sepsis, or meningitis: These clinical entities deserve aggressive intravenous therapy and, occasionally, constant monitoring in an intensive care unit.

Surgical Care:

Empyema requires a chest tube for continuous drainage, and pleural decortication may be indicated.

Other general indications include draining abscesses or closed-space fluid (joints, pericardium, middle ear [rarely]) and bone debridement.

Consultations: Infectious disease consultation in all patients with sepsis, meningitis, empyema, spontaneous bacterial peritonitis, or septic arthritis

MEDICATION Section 7 of 11

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Drug-resistant S pneumoniae strains (DRSP) have become increasingly prevalent worldwide. Rates of decreased penicillin susceptibility have been reported to be much greater than 30% in some US centers and even higher in other countries. There is tremendous variation among different cities and, sometimes, between different populations within the same city.

Isolates that are susceptible to penicillin also are susceptible to nearly all other antibiotics. However, if penicillin MIC rises, the MIC of the most active beta-lactam drugs (cefotaxime, ceftriaxone) also rises. This linear relationship frequently results in decreased susceptibility for the majority of strains of pneumococci that are resistant to a concentration of penicillin of 2 mg/ml or more. The mechanism of resistance to beta-lactams is not mediated by production of enzymes such as beta-lactamases, but involves modifications of some enzymes implicated in the bacterial cell wall synthesis. These enzymes are known as penicillin-binding proteins.

Resistance is widespread with tetracycline, macrolides, trimethoprim-sulfamethoxazole (TMP-SMX), but not with doxycycline or clindamycin.

Fluoroquinolones remain active. However, the excessive use of this class of antimicrobial agents is resulting in developing resistance that is of major concern. Among the respiratory quinolones, moxifloxacin is currently the most active against pneumococci, followed by gatifloxacin. The AUIC (area under the inhibitory concentration curve), which is AUC/MIC (the area under the concentration curve divided by the MIC) recently has been shown to be the best predictor of efficacy for quinolone therapy. An optimal AUIC should be greater than or equal to 125. When the AUIC is greater than 100, the appearance of resistant mutants during therapy is unlikely.

Vancomycin remains fully active against all bacteria.

A difficult problem with the breakpoints is that, clinically, MICs have different meanings according to the site of infection. Intermediate sensitivity does not predict treatment failure for pneumonia, but does for otitis media. Also, ample evidence suggests avoiding the use of penicillin, even in high doses, for the treatment of meningitis caused by nonsusceptible pneumococci. Clearly, the definition of susceptibility should correlate with the site infected. This principle is currently under consideration by the National Committee for Clinical Laboratory Standards (NCCLS), and recommendations probably include multiple disease-based breakpoints. Consequently, a breakpoint of 4 mg/L does appear appropriate for pneumonia, while it should be set at 0.12 mg/L for meningitis.

Treatment of meningitis deserves special consideration. The basic principle of therapy should be to presume nonpenicillin susceptibility, pending susceptibility results. Vancomycin and ceftriaxone or cefotaxime are the initial preferred treatments. This drug regimen may be continued for non–penicillin-susceptible isolates. Meropenem could be an alternative, but there is little clinical experience. Vancomycin does not penetrate the CNS well. Steroids may significantly decrease vancomycin CNS penetration in adults.

Drug Category: Antibiotics -- Penicillins are well tolerated and effective against all susceptible strains of S pneumoniae, and they can be administered orally or parenterally. Never use penicillins to treat meningitis before seeing the isolate susceptibility report or with strains that even have intermediate penicillin susceptibility. They can be used for infections outside the CNS, even for strains with intermediate susceptibility. Most resistant isolates have MICs at or very close to the breakpoint of 2 mg/mL. If administered in high dosage, penicillins/beta-lactams are effective for CAP. No evidence exists in the literature that mortality for pneumococcal pneumonia is related to penicillin resistance. Otitis media and sinusitis deserve special considerations. The empirical antimicrobial treatment used also should be active against bacteria such as H influenzae and Moraxella catarrhalis because a specimen rarely is available for culture and susceptibility.

Amoxicillin is active against most respiratory pathogens. Penicillins associated with beta-lactamase inhibitors (eg, clavulanate, sulbactam, tazobactam) are not discussed because they provide no additional benefit compared to the beta-lactams.

First-generation cephalosporins are equally effective against infections caused by penicillin-susceptible S pneumoniae. All first-generation cephalosporins are equally effective against pneumococci; therefore, only cefazolin and cephalexin are detailed below. Third-generation cephalosporins include ceftriaxone and cefotaxime. These are active against non–penicillin-susceptible S pneumoniae, even though the MIC is higher than the MIC for penicillin-susceptible S pneumoniae. For empiric treatment of meningitis, third-generation cephalosporins may be administered in conjunction with vancomycin or rifampin. Other cephalosporins (eg, cefaclor, cefuroxime, and cefixime) have the same efficacy as cephalexin and cefazolin.

Azithromycin has activity against penicillin-susceptible strains of S pneumoniae. Approximately 25% of S pneumoniae are naturally resistant to all macrolides. The activity of macrolides against nonsusceptible pneumococci is significantly reduced. They are not a therapeutic option for meningitis because they cross the blood-brain barrier poorly. Because of low serum levels, do not use azithromycin as an initial monotherapy for CAP.

Because of their limited activity against S pneumoniae, ciprofloxacin, norfloxacin, and ofloxacin are not acceptable choices for treatment of pneumococcal infections. Levofloxacin and sparfloxacin have good activity against penicillin-susceptible and penicillin-resistant strains. Moxifloxacin is the most active quinolone against pneumococci. They have excellent penetration into lung tissue. Using them excessively for the treatment of pneumococcal infections is discouraged. Resistance to these agents may develop rapidly. A lack of clinical experience precludes the use of IV levofloxacin for the treatment of meningitis. Among the new agents of this class, trovafloxacin and grepafloxacin have been removed from the market because of significant, severe, adverse effects.

Further Inpatient Care:

Pneumonia

Repeat chest radiographs after therapy to evaluate the resolution of the disease.

Once a hospitalized patient is stabilized and has begun to respond, consider stepping the patient down to oral medication.

Meningitis

Continue IV therapy with the meningeal doses for a total of 10-14 days (unless complications require longer treatment).

If the patients' response to therapy is suboptimal or if their condition deteriorates, repeat lumbar puncture.

Further Outpatient Care:

Pneumonia: Repeat chest radiograph, abnormalities can persist for as many as 14 weeks.

Deterrence/Prevention:

Offer the 23-valent vaccine to patients who have not been vaccinated.

With the exception of use in young children, the efficacy and safety of the pneumococcal vaccine has been well demonstrated. The vaccine contains capsular antigens from each of the 23 serotypes most commonly involved in infections in the US.
The pneumococcal 7-valent conjugate is available for the immunization of infants and toddlers against invasive disease caused by capsular serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F of S pneumoniae. In the US, these 7 serotypes have been responsible for more than 80% of invasive pneumococcal disease in children younger than 6 years.

According to the Immunization Practices Advisory Committee of the Center for Disease Control and Prevention, pneumococcal vaccines should be administered to the following individuals:

Persons 65 years or older
Persons aged 2-64 years who have chronic illness that includes chronic cardiovascular disease, chronic pulmonary disease, diabetes mellitus, cirrhosis, alcoholism, or cerebral spinal fluid (CSF) leaks
Persons aged 2-64 years who have functional or anatomic asplenia, persons who are splenectomized, and particularly those suffering from sickle cell disease
Persons aged 2-64 years who are living in a particular environment or social setting that may include Alaskan natives, certain American Indian populations, and residents of nursing homes and other long-term care facilities
Persons who are immunocompromised with illnesses, such as HIV infection, leukemia, lymphoma, Hodgkin disease, multiple myeloma, generalized malignancy, chronic renal failure, nephrotic syndrome, organ or bone marrow transplantation, and persons receiving immunosuppressive chemotherapy (including long-term systemic corticosteroids)
Vaccinate persons without hesitation for whom the vaccination status is unknown.

Revaccination: The duration of protection after vaccination cannot be precisely defined, but it decreases more rapidly in the elderly/compromised hosts.
One revaccination is recommended for persons 2 years or older who are at high risk for serious pneumococci infection and for those who are likely to have a rapid decline in pneumococcal antibody levels, including the following:

Revaccinate children with anatomical or functional asplenia, nephrotic syndrome, renal failure, or renal transplantation 3 years after the initial pneumococcal vaccination.

Other persons who are immunocompromised, including persons older than or equal to 65 years, should be administered a second dose of vaccine 5 years after the initial vaccination.

At present time, the need for subsequent doses of pneumococcal vaccine is unclear. Revaccination 4 or more years after an initial vaccination is not associated with an increased incidence of adverse effects.

Hypogammaglobulinemia: Treat patients with immunoglobulin G deficiency with intravenous immunoglobulins (IVIG at 100-400 mg/kg) every 3-4 weeks. Maintain trough levels of immunoglobulins above 400 mg/dL. This therapy should significantly prevent repeated sinopulmonary infections. Immunoglobulin A (IgA) deficiency deserves special consideration because immunoglobulin E (IgE) antibodies against exogenous IgA may develop and cause anaphylactic reaction. These subjects should not receive immunoglobulin preparations containing IgA. Fortunately, most people with IgA deficiency are clinically normal.

Cigarette smoking: Recently, cigarette smoking has been shown to be the strongest independent risk factor for invasive pneumococcal disease among immunocompetent nonelderly adults in a study by Nuorti et al conducted in the metropolitan areas of Atlanta, Baltimore, and Toronto. Consequently, programs to reduce both smoking and exposure to environmental tobacco smoke have the potential to reduce the incidence of pneumococcal disease.

Complications:

Pneumonia: Pleural effusion may occur in some cases of pneumococcal pneumonia.

Pleural effusions usually are small and self-limited.

For empyema, frank pus is a characteristic finding. Pleural fluid cultures and Gram stain are frequently positive. Pleural fluid loculation is seen with empyema. Besides antibiotics administration, tube drainage is indicated for empyema. Decortication by thoracoscopy or thoracotomy occasionally is indicated for empyema and extremely complex exudates.

Meningitis

If present, cranial nerve palsies (III, VI, VII, VIII) usually disappear within a few weeks. Approximately 10% of infants and children are left with persistent unilateral or bilateral sensory hearing loss.

Vasculitis and cerebral infarction are causes of focal and lateralizing neurologic signs, epilepsy, and mental retardation.

For obstructive hydrocephalus and subdural empyema, shunting or surgical drainage is mandatory.

Prognosis:

For pneumonia, the prognosis varies widely with age and host factors.

Meningitis

Of the common forms of meningitis, pneumococcal meningitis has a high incidence of neurologic sequelae.

Other conditions, such as alcoholism, head trauma, multiple myeloma, HIV infection, and asplenia, are prognostic factors.

Patient Education:

Patients suffering from medical conditions that predispose them to or aggravate pneumococcal infections should be informed about the morbidity and mortality of pneumococcal infections and seek early medical attention. They should be aware that the pneumococcal vaccine may prevent such infections.

MISCELLANEOUS

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Medical/Legal Pitfalls:

Recognize severe pneumonia in patients who are elderly or debilitated and may not look sick enough to have pneumococcal pneumonia.

Treat pneumococcal meningitis with antibiotics with in vitro activity that crosses the blood-brain barrier (ie, third-generation cephalosporins).

Appropriately investigate young persons with repeated episodes of pneumococcal infections. Such persons could suffer from immunoglobulin deficiency (common variable, hypogammaglobulinemia being the most frequent) and benefit from regular administration of IV immunoglobulin.

PICTURES

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Caption: Picture 1. Sputum Gram stain from a patient with a pneumococcal pneumonia. Note the numerous polymorphonuclear neutrophils and gram-positive, lancet-shaped diplococci. Courtesy of C. Sinave, MD, personal collection.
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Picture Type: Photo

Caption: Picture 2. Lobar consolidation with pneumococcal pneumonia. Posteroanterior film. Courtesy of R. Duperval, MD.
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Picture Type: X-RAY

Caption: Picture 3. Lobar consolidation with pneumococcal pneumonia. Lateral film. Courtesy of R. Duperval, MD.
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Picture Type: X-RAY

Caption: Picture 4. Empyema caused by Streptococcus pneumoniae. Anteroposterior film. Courtesy of R. Duperval, MD.
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Picture Type: X-RAY

Caption: Picture 5. Purpura due to pneumococcal sepsis in a 39-year-old man who had a splenectomy 20 years earlier. Courtesy Thomas Herchline, MD, Wright State University, Dayton, Ohio.
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Picture Type: Photo

BIBLIOGRAPHY Section 11 of 11

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Advisory Committee on Immunization Practices (ACIP): Prevention of pneumococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 1997 Apr 4; 46(RR-8): 1-24 [Medline].
Bonoan JT, Cunha BA: S. aureus as a cause of Community-acquired pneumonia in patients with diabetes mellitus. Infect Dis Clin Pract 1999; 8: 319-321.
Bonoan JT, Cunha BA: Pulmonary toxicity of granulytic stimulating factor (GCSF) in treating Community-acquired pneumonia. Antibiotics for Clinicians 1998; 2: 18-20.
Bryant RE, Salmon CJ: Pleural empyema. Clin Infect Dis 1996 May; 22(5): 747-62; quiz 763-4[Medline].
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Pneumococcal Infections excerpt