AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Streptococcus pneumoniae colonizes the upper respiratory tract of healthy individuals, and it is one of the most frequent causes of bacterial infection in children. Common infections caused by this pathogen include otitis media (OM), sinusitis, occult bacteremia, pneumonia, and meningitis. Pneumococci also may cause osteomyelitis, septic arthritis, pericarditis, and peritonitis.

Pathophysiology

Pneumococci are encapsulated, lancet-shaped, gram-positive diplococci. The bacteria are transmitted person to person via respiratory droplet contact. Pneumococci can cause disease either by direct spread from colonized mucosal surfaces (eg, otitis media) or by hematogenous spread (eg, meningitis following bacteremia). Mucosal irritation resulting from factors such as viral infection or smoke often is a predisposing factor for pneumococcal infection. Ninety serotypes have been identified, with varying degrees of pathogenicity. Serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F cause the majority of invasive disease, and pneumococci with these serotypes often are resistant to penicillin.

Frequency

United States

Invasive disease is most frequent in children younger than 2 years and in adults older than 65 years. Overall annual incidence of invasive disease in the United States is 15 cases per 100,000 individuals, but it varies greatly by age, from 166 cases per 100,000 children younger than 2 years to 5 cases per 100,000 young adults. After the introduction of heptavalent conjugated pneumococcal vaccine, the rate of invasive pneumococcal disease (IPD) has trended down. In an active laboratory surveillance from 1997-2004, the IPD decreased by 40% from 11.8 cases to 7.2 cases per 100,000 live births. Among African American infants a marked decrease was noted in incidence of IPD from 17.1 cases to 5.3 cases per 100,000 live births compared with white infants with a decrease from 9.6 cases to 6.8 cases per 100,000 live births.

An increased frequency of disease and increased morbidity and mortality rates are seen in children younger than 2 years and in children with humoral immunodeficiency (eg, HIV infection, agammaglobulinemia, complement deficiency), absent or deficient splenic function (eg, splenectomy, sickle cell anemia), nephrotic syndrome, chronic renal failure, organ transplantation, chronic pulmonary disease, cerebral spinal fluid (CSF) leak after skull fracture, and malignancy. Parental smoking invariably increases acute OM by about 64% compared to no history of parental smoking (56%).

Specific infections

Otitis media: Approximately 30% of children have at least one episode of pneumococcal OM by age 3 years. Pneumococci cause approximately 40% of OM cases. After the pneumococcal vaccination, nonvaccine serotype is encountered more frequently as a cause of otitis compared with vaccine serotypes.

Bacteremia: Pneumococci are responsible for as many as 85% of occult cases of bacteremia in children. Bacteremia is seen in 3-5% of children aged 3-36 months with fever higher than 102.5°F without another source. In the postvaccine licensure period, the annual episodes of pneumococcal bacteremia decreased from 7.2 episodes to 2.3 episodes per 100,000 emergency department visits in 1999. However, it increased to 2.8 episodes in 2004 and to 3.64 episodes per 100,000 emergency department visits in 2005. The rate of invasive disease due to serotype 19F in the conjugate vaccine has increased.

Pneumonia: S pneumoniae is the most common bacterial cause of childhood pneumonia, especially in children younger than 5 years.

Meningitis/central nervous system (CNS) infections: S pneumoniae is the most common cause of bacterial meningitis in children. Yearly incidence in all age groups is 1-2 cases per 100,000 population.

Osteomyelitis/septic arthritis: Pneumococci are responsible for fewer than 10% of all cases of osteomyelitis and septic arthritis.

Other unusual infections caused by pneumococci are sporadic.

The recent inclusion of the pneumococcal conjugate vaccine in the routine pediatric immunization schedule has decreased the incidence of invasive pneumococcal disease markedly. The vaccine is about 50-60% efficacious in reducing OM caused by the vaccine strains of S pneumoniae compared with 80-100% in preventing invasive disease (IPD).

International

Pneumococcal pneumonia is estimated to cause 1.2 million deaths per year worldwide in children younger than 5 years.

Mortality/Morbidity

• Death resulting from complications of pneumococcal otitis, sinusitis, bacteremia, and pneumonia is rare in otherwise healthy children. As a complication of pneumonia, pneumococcal empyema is not infrequent, even in developed countries, and it remains a significant problem in developing nations.
• The case-fatality rate for pneumococcal meningitis is 5-10%. Between 25 and 35% of children with pneumococcal meningitis develop permanent neurologic sequelae (eg, hearing deficits, paralysis, hydrocephalus).
• The risk of fulminant pneumococcal infection and death in the high-risk patient population outlined above (eg, children with humoral immunodeficiency, functional asplenia, nephrotic syndrome) is much higher than the risk in otherwise healthy children.

Race

An increased incidence of invasive pneumococcal disease has been documented in African Americans, American Indians (white Mountain Apache, Navajo), and Alaskan Eskimos.

Sex

Pneumococcal disease is slightly more frequent in males than in females, with a male-to-female ratio of 3:2 for pneumococcal bacteremia.

Age

Pneumococcal infections are most common in children aged 1-24 months.

• OM and bacteremia are most common in children aged 6 months to 2 years.
• Sinusitis is most common in children 2 years and older.
• Pneumonia and meningitis are most common in children younger than 5 years.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Children with pneumococcal infections usually have a temperature higher than 102°F. Children with invasive infections also demonstrate signs and symptoms related to the site of infection. Symptoms of specific infections in addition to fever are as follows:

• Otitis media
• • Otalgia (irritability and ear pulling in younger children)
  • Upper respiratory symptoms
  • Vomiting
• Sinusitis
• • Headache
  • Facial tenderness (much less frequent than in adults)
  • Symptoms of upper respiratory infection (cough, nasal drainage, congestion) lasting for 10 days or longer
• Occult bacteremia - Fever without a localizing source in children aged 2-24 months
• Pneumonia
• • Cough
  • Chest pain, shortness of breath, or respiratory difficulty
  • Malaise and poor appetite
• Meningitis
• • Stiff neck
  • Vomiting
  • Headache (older children)
  • High fever (temperature >103°F)
  • Lethargy
  • Irritability
  • Poor feeding
  • Unconsolable crying

Physical

• Otitis media - Bulging, erythematous, or yellow tympanic membrane with poor mobility and purulent fluid seen behind the tympanic membrane
• Sinusitis
• • Tenderness to palpation over maxillary or frontal sinuses
  • Nasal discharge of any color
  • Swollen nasal turbinates
• Bacteremia - No physical findings except fever (temperature of 102°F or higher) and tachycardia associated with the fever
• Pneumonia
• • Crackles or decreased breath sounds in the area of lobar consolidation on chest auscultation, with egophony in patients with severe consolidation and dullness to percussion
  • Retractions, tachypnea, or both
• Meningitis/CNS infections
• • Ill appearance
  • Nuchal rigidity (may not be present in infants <4 mo)
  • Altered mental status, poorly responsive (patient may present in comatose state)
  • Other neurologic abnormalities possible, such as cranial nerve deficits, ataxia, and weakness
  • Poor perfusion and signs of shock in patients with concurrent pneumococcal sepsis

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• White blood cell count
• • Elevated WBC count and differential showing a high band count or left shift may suggest bacterial infection.
  • Young children with a WBC count greater than 15,000 cells/mL and/or an absolute band count greater than 1500/mcL have an increased likelihood of occult bacteremia.
  • WBC count may be low in children with meningitis and other severe pneumococcal infections.
• Antigen tests
• • Use of CSF and urine antigen tests for pneumococci is limited because of the multitude of S pneumoniae serotypes and the poor sensitivity of the test. At present, these tests should be used only in children in whom blood and CSF cultures were obtained after antibiotic treatment. In these children, antigen test results occasionally are positive when culture results are negative.
  • A negative result on an antigen test does not exclude pneumococcal infection.
• Gram stain
• • Gram stains of usually sterile body fluids (CSF, synovial fluid, pleural fluid) showing gram-positive diplococci strongly suggest the diagnosis of pneumococcal infection, although alpha-hemolytic streptococci and group B streptococci can look like S pneumoniae.
  • Results of CSF Gram stains in younger children with meningitis are positive 90-100% of the time, but the CSF Gram stain technique may be slightly less sensitive in older children.
• Culture
• • Culture of S pneumoniae from usually sterile body fluids (eg, blood, CSF, pleural fluid, middle ear effusion, synovial fluid) establishes the diagnosis definitively.
  • Perform susceptibility testing when an invasive infection is present.
• For each of the following clinical syndromes, specific testing recommendations are as follows:
• • Otitis media or sinusitis
    • Tympanocentesis and bacterial cultures of middle ear fluid should be performed in children with chronic otitis media refractory to antibiotic treatment. This requires technical expertise.
    • Sinus fluid should be obtained and sent for bacterial culture if the sinusitis is refractory to antibiotic treatment.
    • Upper respiratory tract cultures are not reliable in determining infection because of the high rate of asymptomatic children carrying S pneumoniae.
  • Occult bacteremia - Blood culture of sufficient volume (minimum of 2 mL)
• Pneumonia
• • Sputum cultures are difficult to obtain from children, and results may be falsely positive because of the high rates of upper respiratory colonization in this population.
  • Blood cultures should be obtained in all patients, although only 25-30% of patients with pneumococcal pneumonia have positive results on blood culture.
• Meningitis
• • When meningitis is suspected, lumbar puncture should be performed. CSF should be sent for cell count, protein levels, glucose levels, Gram stain, and culture. Antigen tests are needed only if the patient was pretreated with antibiotics.
  • A blood culture also should be obtained to further confirm the diagnosis and the pathogens.
• Osteomyelitis/septic arthritis
• • Procedures include surgical biopsy or joint aspiration; fluid or bone is cultured for the organism.
  • Perform blood culture, since bacteremia often is present as well.

Imaging Studies

• Chest radiographs may show lobar or segmental consolidation or typical findings of round pneumonia.
• In many centers, a head CT scan is performed in older children with meningitis to exclude increased intracranial pressure prior to performing lumbar puncture. No compelling evidence exists that CT findings are better than physical examination at predicting complications from lumbar puncture, and, in most patients, a CT scan causes unnecessary delay of lumbar puncture. In young children with an open fontanelle, a head CT scan is unnecessary unless physical findings suggest complications or a diagnosis other than meningitis. In children with persistent fevers despite appropriate antimicrobial therapy, a head CT scan, or preferably an MRI, should be performed to exclude subdural empyema. MRI is more sensitive than CT in the detection of subdural or epidural empyema.

Procedures

• Lumbar puncture

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• Antibiotic therapy (see Medication)
• Supportive care

Consultations

• Surgeon: Children with septic arthritis, osteomyelitis, subdural effusion with meningitis, mastoiditis, or other unusual invasive infections require appropriate surgical consultation.
• Infectious disease specialist: A specialist in pediatric infectious diseases should be consulted when treating children with complicated pneumococcal infections or invasive pneumococcal disease caused by drug-resistant S pneumoniae.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Many pneumococcal strains are resistant to penicillin (8-40%, depending on geographic location), and resistance to ceftriaxone also is increasing. Therapy must be altered accordingly. Nonsusceptibility to penicillin and trimethoprim/sulfamethoxazole has increased from 25% and 18%, respectively, in the prepneumococcal vaccine (PCV7) era to 39% and 29%, respectively, in the postvaccination period.

When a strain is resistant to penicillin and cephalosporins, it often is also resistant to erythromycin, trimethoprim-sulfamethoxazole, and tetracyclines. Resistance is seen most often in serotypes 6, 9, 14, 19, and 23.

Penicillin-resistant strains are defined as intermediately resistant (minimum inhibitory concentration [MIC] >0.1-1 mcg/mL) or highly resistant (MIC >2 mcg/mL). The susceptibility to cefotaxime or ceftriaxone is based on location of isolation of the organism.

The key to successful antibiotic therapy of pneumococcal disease is achieving drug concentrations in the affected area of the body that are several times higher than the MIC of the organism.

Beta-lactam antibiotics (eg, amoxicillin, cefuroxime) achieve high levels in middle ear fluid and in the respiratory tract. For this reason, they remain the drugs of choice for OM and sinusitis, even when these infections are caused by penicillin-resistant pneumococci. Amoxicillin is the drug of choice for susceptible strains causing most noninvasive disease (eg, OM, sinusitis) and for outpatient treatment of pneumonia. High-dose amoxicillin (80-90 mg/kg/d) also can be used for OM, sinusitis, and pneumonia caused by penicillin-resistant pneumococci with intermediate resistance.

In the CNS, a drug concentration 8- to 15-fold higher than the minimum bactericidal concentration (MBC) is required for eradication of meningitis. Initial empiric therapy should include cefotaxime (225-300 mg/kg/d divided q8h) or ceftriaxone (100 mg/kg/d divided q12-24h) along with vancomycin (60 mg/kg/d divided q6h). Ceftriaxone is the drug of choice for meningitis caused by ceftriaxone-susceptible pneumococci (MIC <0.5 mcg/mL).

Meropenem may be an alternative to ceftriaxone for ceftriaxone-resistant pneumococcal meningitis. If the MIC to meropenem is greater than 0.12 mcg/mL, vancomycin should be used in addition to meropenem.

For nonmeningeal invasive pneumococcal disease including disease caused by penicillin- and ceftriaxone-resistant pneumococci, ceftriaxone is the drug of choice if the organism's MIC to ceftriaxone is less than 4 mcg/mL. For organisms with an MIC of 4 mcg/mL or higher, vancomycin probably should be used in addition to ceftriaxone.

Drug Category: Antibiotic agents

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Drug Name	Ceftriaxone (Rocephin)
Description	Third-generation cephalosporin. DOC for meningitis (age > 1 mo), inpatient treatment of pneumonia, occult bacteremia, and other invasive infections. Alternative for outpatient treatment of occult bacteremia and OM unresponsive to standard antibiotics.
Adult Dose	1-4 g/d IV/IM divided q12-24h; not to exceed 4 g/24 h
Pediatric Dose	50-75 mg/kg/d IM/IV divided q12-24h Meningitis (including penicillin-resistant strains): 100 mg/kg/d IV divided q12h administered with vancomycin Non-CNS infections caused by penicillin-resistant strains: 80-100 mg/kg/d IV divided q12-24h Acute OM: 50 mg/kg IM as single dose Acute OM refractory to prior antibiotic treatment: 50 mg/kg/d IM for 3 d Occult bacteremia: 50 mg/kg/d IM Note: Not to exceed 1 g/dose
Contraindications	Documented hypersensitivity
Interactions	Probenecid may increase ceftriaxone levels; coadministration with ethacrynic acid, furosemide, and aminoglycosides may increase nephrotoxicity
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust in renal impairment; caution in infants <4 wk because of risk of hyperbilirubinemia (consider alternative cephalosporin, eg, cefotaxime)

Drug Name	Cefotaxime (Claforan)
Description	Third-generation cephalosporin. DOC for meningitis (all ages), inpatient treatment of pneumonia, bacteremia, and other invasive infections.
Adult Dose	Standard dose: 1-2 g/dose IV/IM q6-8h Meningitis or other severe infection: 2 g/dose IV/IM q4-6h Note: Not to exceed 12 g/d
Pediatric Dose	Neonates (dose based on postnatal age and weight): <7 days and <2000 g: 100 mg/kg/d IV/IM divided q12h <7 days and >2000 g: 100-150 mg/kg/d IV/IM divided q8-12h 7-28 days and <1200 g: 100 mg/kg/d IV/IM divided q12h 7-28 days and >1200 g: 150 mg/kg/d IV/IM divided q8h Infants > 4 weeks and children: 100-200 mg/kg/d IV/IM divided q8h Meningitis: 200 mg/kg/d IV/IM divided q6h Non-CNS penicillin-resistant infections: 150-225 mg/kg/d IV/IM divided q6-8h Penicillin-resistant CNS/meningitis: 225-300 mg/kg/d IV/IM q6-8h administered with vancomycin
Contraindications	Documented hypersensitivity
Interactions	Probenecid may increase cefotaxime levels; coadministration with furosemide and aminoglycosides may increase nephrotoxicity
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Possible neutropenia, thrombocytopenia, eosinophilia, positive Coombs test result, elevated BUN level, creatinine level, and liver enzyme level; dose adjustment needed in renal failure

Drug Name	Vancomycin (Vancocin)
Description	DOC for initial treatment of all meningitis (with cefotaxime or ceftriaxone) until susceptibilities are known. Continue in addition to ceftriaxone if the organism's ceftriaxone MIC is >0.25 mcg/mL. Also consider adding for non-CNS invasive infections if not responding to standard treatment because the infection may be caused by highly penicillin-resistant strains. DOC for patients allergic to penicillin with meningitis (with rifampin) or other invasive infections (alone).
Adult Dose	2 g/d IV divided q6-12h
Pediatric Dose	Neonates (dose based on postnatal age and weight): <7 days and <1200 g: 15 mg/kg/dose/d IV <7 days and 1200-2000 g: 10-15 mg/kg/dose IV q12-18h <7 days and >2000 g: 10-15 mg/kg/dose IV q8-12h 7-28 days and <1200 g: 15 mg/kg/dose/d IV 7-28 days and 1200-2000 g: 10-15 mg/kg/dose IV q8-12h 7-28 days and >2000 g: 15-20 mg/kg/dose IV q8h Infants > 4 weeks and children: 40 mg/kg/d IV divided q6-8h CNS infections: 60 mg/kg/d IV divided q6-8h Note: Not to exceed 2 g/24 h
Contraindications	Documented hypersensitivity
Interactions	Erythema, histaminelike flushing, and anaphylactic reactions may occur when administered with anesthetic agents; taken concurrently with aminoglycosides, risk of nephrotoxicity may increase above risk with aminoglycoside monotherapy; effects in neuromuscular blockade may be enhanced when coadministered with nondepolarizing muscle relaxants
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Possibility of ototoxicity and nephrotoxicity; possible exacerbation by concurrent aminoglycosides; dose adjustment needed in renal failure; possible red man syndrome with rapid IV infusion; infuse over 60-120 min for safety; monitor serum levels to avoid toxicity and ensure therapeutic levels (obtain trough level 30 min prior to dose 3, obtain peak level 60 min after dose 5); desired peak level is 25-40 mg/L and desired trough level is <10 mg/L; for meningitis, desired peak level is a minimum of 30 mg/L; when coadministered with aminoglycosides, monitor serum levels of both drugs and creatinine daily

Drug Name	Azithromycin (Zithromax)
Description	Alternative for patients allergic to penicillin with OM, sinusitis, or outpatient treatment of pneumonia.
Adult Dose	500 mg PO on day 1, then 250 mg/d PO on days 2-5
Pediatric Dose	10 mg/kg/dose PO day 1, then 5 mg/kg/d PO on days 2-5; not to exceed 250 mg/d
Contraindications	Documented hypersensitivity; hepatic impairment; do not administer with pimozide
Interactions	May increase toxicity of theophylline, warfarin, and digoxin; effects are reduced with coadministration of aluminum and/or magnesium antacids; nephrotoxicity and neurotoxicity may occur when coadministered with cyclosporine
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	May increase hepatic enzymes and cholestatic jaundice; caution in patients with impaired hepatic function, prolonged QT intervals, or pneumonia; caution in hospitalized, geriatric, or debilitated patients

Drug Name	Clindamycin (Cleocin)
Description	Alternative treatment for OM or sinusitis unresponsive to standard treatment. Alternative also for OM, sinusitis, and inpatient or outpatient treatment of pneumonia and treatment of invasive infections other than CNS infections in patients who are allergic to penicillin.
Adult Dose	150-450 mg/dose PO q6-8h; not to exceed 1.8 g/d 1200-1800 mg/d IM/IV divided q6-12h; not to exceed 4.8 g/d
Pediatric Dose	Neonates: 5 mg/kg/dose q6-12h (longer interval if weight <2 kg) Infants > 4 weeks and children: 30 mg/kg/d PO divided q6-8h 40 mg/kg/d IV/IM divided q6-8h
Contraindications	Documented hypersensitivity; hepatic impairment; antibiotic-associated colitis; CNS infections
Interactions	Increases duration of neuromuscular blockade induced by tubocurarine and pancuronium; erythromycin may antagonize effects of clindamycin; antidiarrheals may delay absorption of clindamycin
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Possibility of pseudomembranous colitis up to several weeks after cessation of therapy; possible diarrhea, rash, Stevens-Johnson syndrome, granulocytopenia, thrombocytopenia, or sterile abscess at injection site; not to exceed infusion rate of 30 mg/min; possible hypotension or cardiac arrest; do not use in CNS infections (poor CNS penetration)

Drug Name	Meropenem (Merrem IV)
Description	A carbapenem antibiotic alternative for patients allergic to penicillin with meningitis or other severe invasive infections (good CSF penetration). Has been used successfully in patients with meningitis caused by penicillin-resistant pneumococci.
Adult Dose	1.5-3 g/d IV divided q8h Meningitis and severe infections: 6 g/d IV divided q8h
Pediatric Dose	<3 months: Not established >3 months and children: 60 mg/kg/d IV divided q8h; not to exceed 3 g/d Meningitis: 120 mg/kg/d IV divided q8h; not to exceed 6 g/d
Contraindications	Documented hypersensitivity
Interactions	Probenecid may inhibit renal excretion of meropenem, increasing meropenem levels
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Possible diarrhea, rash, vomiting, oral moniliasis, glossitis, pain and irritation at IV injection site, and headache; possible hepatic enzyme elevation, bilirubin elevation, leukopenia, and neutropenia; dose adjustment needed in renal impairment; use in meningitis only if organism is susceptible to meropenem (MIC <0.12 mcg/mL)

Drug Name	Rifampin (Rifadin)
Description	Used in conjunction with vancomycin for patients allergic to penicillin with meningitis.
Adult Dose	600-1200 mg/d IV divided q12h
Pediatric Dose	20 mg/kg/d IV divided q12h
Contraindications	Documented hypersensitivity
Interactions	Induces CYP450 microsomal enzymes, which may decrease effects of acetaminophen, oral anticoagulants, barbiturates, benzodiazepines, beta-blockers, chloramphenicol, oral contraceptives, corticosteroids, mexiletine, cyclosporine, digitoxin, disopyramide, estrogens, hydantoins, methadone, clofibrate, quinidine, dapsone, tazobactam, sulfonylureas, theophyllines, tocainide, and digoxin; blood pressure may increase with coadministration of enalapril; coadministration with isoniazid may result in higher rate of hepatotoxicity than with either agent alone (discontinue one or both agents if alterations occur in LFTs)
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Obtain CBCs and baseline clinical chemistry panels prior to and throughout therapy; in liver disease, weigh benefits against risk of further liver damage; interruption of therapy and high-dose intermittent therapy are associated with thrombocytopenia that is reversible if therapy is discontinued as soon as purpura occurs; if treatment is continued or resumed after appearance of purpura, cerebral hemorrhage or death may occur

Drug Name	Amoxicillin-clavulanic acid (Augmentin)
Description	Antibiotic with beta-lactam inhibitor. Alternative for OM or sinusitis unresponsive to standard treatment. In children > 3 mo, base dosage protocol on amoxicillin content. As a result of different amoxicillin–to–clavulanic acid ratios in 250-mg tab (250/125) vs 250-mg chewable tab (250/62.5), do not use 250-mg tab until child weighs >40 kg.
Adult Dose	250-500 mg/dose PO tid or 750 mg/dose PO bid
Pediatric Dose	Based on amoxicillin component: <3 months: 30 mg/kg/d PO divided bid >3 months: 20-40 mg/kg/d PO divided tid or 25-45 mg/kg/d PO divided bid
Contraindications	Documented hypersensitivity; sensitivity to phenylketonurics (bid dosage form contains phenylalanine)
Interactions	Coadministration with warfarin or heparin increases risk of bleeding
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Dose adjustment needed with renal impairment

Drug Name	Cefprozil (Cefzil)
Description	Alternative for OM or sinusitis unresponsive to standard treatment or in patients with penicillin allergy but no cephalosporin allergy. Alternative outpatient treatment for pneumonia.
Adult Dose	500-1000 mg/d PO divided q12h
Pediatric Dose	30 mg/kg/d PO divided q12h; not to exceed 1 g/d
Contraindications	Documented hypersensitivity; caution with penicillin allergy
Interactions	Probenecid increases effect of cefprozil; coadministration with furosemide and aminoglycosides increases nephrotoxic effects of cefprozil
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Dose adjustment needed with renal failure

Drug Name	Cefepime (Maxipime)
Description	Fourth-generation cephalosporin with good gram-negative coverage. Similar to third-generation cephalosporins but has better gram-positive coverage. Has good pneumococcal coverage and penetrates the CSF well, thus, can be used as alternative to ceftriaxone.
Adult Dose	1-2 g IV q12h for 10 d
Pediatric Dose	50 mg/kg IV q8h; not to exceed 2 g/dose
Contraindications	Documented hypersensitivity
Interactions	At high doses, probenecid decreases cefepime clearance; when used concurrently, aminoglycosides increase nephrotoxic potential of cefepime
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in severe renal insufficiency; prolonged use of cefepime may predispose patients to superinfection

Drug Name	Cefuroxime (Kefurox, Zinacef, Ceftin)
Description	Second-generation cephalosporin good for treatment of non-CNS pneumococcal disease
Adult Dose	250-500 mg PO bid 750 mg to 1.5 g IV q8h
Pediatric Dose	30 mg/kg/d PO divided bid; not to exceed 1 g/d 150 mg/kg/d IV divided q8h; not to exceed adult dose
Contraindications	Documented hypersensitivity
Interactions	Disulfiramlike reactions may occur when alcohol is consumed within 72 h after taking cefuroxime; may increase hypoprothrombinemic effects of anticoagulants; may increase nephrotoxicity in patients receiving potent diuretics, such as loop diuretics; coadministration with aminoglycosides increase nephrotoxic potential
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Administer one-half dose if creatinine clearance is 10-30 mL/min and one-quarter dose if <10 mL/min; fungal and microorganism overgrowth may occur with prolonged therapy

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Meningitis
• • ICU admission is recommended initially for all patients with bacterial meningitis.
  • Consider a second lumbar puncture at 24-48 hours to evaluate therapy if patient is not improving. A repeat lumbar puncture should be performed in all patients with penicillin-resistant pneumococcal meningitis.
  • If the pneumococcal isolate is found to be susceptible to ceftriaxone (MIC <0.5), discontinue vancomycin. If the isolate is resistant to ceftriaxone, continue vancomycin and ceftriaxone.
  • Daily fluid intake and output should be recorded in children with meningitis, and daily electrolyte levels tested during the acute phase of the illness, since children are at risk for SIADH and resultant hyponatremia. Most experts now agree that children with meningitis should receive regular maintenance intravenous or oral fluids rather than fluid restriction, but fluid intake and output still should be recorded carefully.
  • Children with meningitis should be observed for signs of hydrocephalus. In the young child with an open fontanelle, daily head circumference measurements and palpation of the fontanelle should be performed. Older children should be observed for signs and symptoms of hydrocephalus.
  • All children with meningitis should undergo hearing tests.
  • Dexamethasone therapy started prior to antibiotics and administered for 4 days decreased the frequency of hearing loss in children with meningitis caused by Haemophilus influenzae. Smaller studies have documented a decreased frequency of hearing loss in children and adults with pneumococcal meningitis who were treated with dexamethasone. Dexamethasone dosing is 0.6 mg/kg/d divided q6h for 4 days. However, dexamethasone may decrease CSF concentrations of vancomycin; therefore, use of dexamethasone in regions with a high prevalence of penicillin-resistant pneumococci is controversial.

Further Outpatient Care

• Discharged patients treated for invasive disease should have outpatient follow-up care at 24-48 hours.

In/Out Patient Meds

• Initial treatment of OM or sinusitis: Administer amoxicillin for 5-10 days (OM) or 10-21 days (sinusitis).
• Treatment of OM or sinusitis that has failed to improve clinically using standard-dose amoxicillin treatment: Administer high-dose amoxicillin, amoxicillin-clavulanic acid (Augmentin), cefuroxime, or ceftriaxone (IM).
• Occult bacteremia (with positive culture results): See Pneumococcal Bacteremia.
• Outpatient pneumonia: Administer amoxicillin for 10 days.
• Inpatient pneumonia
• • Administer intravenous ceftriaxone until the child has improved clinically, with a subsequent outpatient regimen for a total of 10 days of treatment.
  • For critically ill patients, the addition of vancomycin should be considered, but most pneumococci causing non-CNS disease, even penicillin-resistant strains, should respond to high-dose ceftriaxone.
• Other invasive pneumococcal diseases
• • Administer third- or fourth-generation parenteral cephalosporins (ceftriaxone, cefotaxime, cefepime).
  • If a patient is critically ill at presentation or not clinically improving, consider adding vancomycin until susceptibilities are known.
• Meningitis in children older than 1 month
• • Ceftriaxone or cefotaxime are the drugs of choice because they have the best CSF penetration.
  • For meningitis, always add vancomycin until susceptibilities are known.
  • After 24-48 hours of therapy, adding rifampin to vancomycin therapy may be considered if (1) clinical worsening is noted, (2) the follow-up CSF does not show eradication of organism or decrease in bacterial load, or (3) MIC of pneumococci to cefotaxime is >4.0.
• Patients allergic to penicillin
• • OM, sinusitis, outpatient treatment of pneumonia: Administer azithromycin (or other macrolide), clindamycin (if not allergic to cephalosporins), cefuroxime, or cefprozil.
  • Inpatient treatment of pneumonia or other invasive infections: Administer intravenous ceftriaxone if the patient is not allergic to cephalosporins. If the patient is allergic to cephalosporins, administer intravenous clindamycin or meropenem. Meropenem has 5-10% cross-reactivity with beta-lactams; therefore, hypersensitivity testing may need to be performed if the allergy is severe. Consider adding vancomycin if the patient is severely ill and organism susceptibility is not known.
  • Meningitis: Administer vancomycin plus rifampin or meropenem (patients > 3 mo).

Transfer

• In hospitals without a pediatric ICU, consider transfer of patients with meningitis or critically ill patients with other invasive disease.
• Also consider transfer if subspecialty surgical consultation may be needed (osteomyelitis, septic arthritis, mastoiditis, other unusual invasive disease).

Deterrence/Prevention

• Pneumococcal vaccination
• • In March 2000, the US Food and Drug Administration approved a heptavalent protein-conjugate vaccine safe for use in children as young as 6 weeks. The new heptavalent conjugate vaccine has been recommended by the American Academy of Pediatrics Advisory Committee on Immunization Practices for all children younger than 2 years and for high-risk children (see Frequency) aged 2-5 years. The vaccine has been shown in several large-scale trials to markedly reduce the number of cases of meningitis and bacteremic pneumonia. The vaccine was less efficacious in reducing OM. Children should receive the pneumococcal vaccine at age 2, 4, 6, and 12-15 months.
  • The older 23-valent pneumococcal polysaccharide vaccine is effective and safe in children older than 5 years. It can be used in children at high risk for invasive pneumococcal disease who have not received the conjugate vaccine. Further study is required to determine whether high-risk children who have received the conjugate vaccine will require revaccination in later years and which vaccine they should receive if revaccination is necessary.

Complications

• Meningitis - Subdural empyema, hydrocephalus, hearing loss, developmental delay, spasticity, mental retardation, and neurologic weakness
• Otitis media - Mastoiditis and cavernous sinus thrombosis
• Sinusitis - Intracranial abscess, periorbital/orbital cellulitis, subperiosteal abscess, cavernous sinus or sagittal sinus thrombosis, and meningitis
• Bacteremia - Osteomyelitis, endocarditis, and meningitis

Prognosis

• See Mortality/Morbidity.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• The major medical-legal pitfall in pneumococcal infections is failure to diagnose meningitis. With the exception of very young children (<6 wk), the diagnosis is usually strongly evident by history and physical examination. In addition, osteomyelitis and septic arthritis occasionally are difficult to diagnose and can be overlooked. Fortunately, pneumococci is not a frequent cause of these conditions.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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Article Last Updated: Sep 21, 2006