Bacteremia Follow-up

Updated: Sep 08, 2017
  • Author: Nicholas John Bennett, MBBCh, PhD, MA(Cantab), FAAP; Chief Editor: Russell W Steele, MD  more...
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Follow-up

Further Outpatient Care

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  • Follow-up care: Febrile infants and young children who have a known source for their fever, such as a recognizable viral infection, soft tissue infection, pneumonia, or UTI, should be monitored based on guidelines for those specific infections. Febrile infants and young children who have been evaluated and found to have FWS should be closely observed and reevaluated in 24 hours. This can be conducted on an inpatient (see Further Inpatient Care) or outpatient basis, with or without blood cultures and antibiotics.

  • Antibiotic treatment at follow-up: The 1993 AAP guidelines recommend that all children at risk for occult bacteremia be reevaluated in 18-24 hours. For children who remained asymptomatic, continued to have nonfocal examination findings, and had blood cultures that were negative for known bacterial pathogens at 24 hours, a second dose of intramuscular ceftriaxone (50 mg/kg) is recommended to cover for a total of 48 hours of negative cultures. [10]

  • Monitoring blood cultures: In addition to reevaluating the patient in 24 hours, monitoring blood cultures is important in detecting occult bacteremia and preventing sequelae of subsequent focal infections. A recent review stated that 50% of patients with serious complications from occult bacteremia returned for evaluation and treatment because of a blood culture positive for known bacterial pathogens; only 12% returned because of illness. [1] For adequate outpatient follow-up and monitoring of blood culture results, the laboratory must be able to contact the physician, the physician must be able to contact the family, and the family must be able to seek care as soon as the blood culture becomes positive for known bacterial pathogens.

  • Blood cultures positive for known bacterial pathogens: Patients who are evaluated for FWS and are monitored as outpatients with blood cultures must be reevaluated if the blood cultures become positive with a known pathogen. The appropriate treatment depends on the clinical situation and the specific bacteria present.

    • S pneumoniae

      • Infants and young children with occult pneumococcal bacteremia may be treated and monitored as outpatients if they are well-appearing and afebrile on follow-up. [1, 6, 10] Treatment recommendations include a second dose of ceftriaxone with the addition of an oral antibiotic when sensitivities are known or with the empiric addition of an oral antibiotic on day 2. [1, 6, 10] Therapy with ceftriaxone is recommended if concern penicillin-resistant pneumococcus is a concern because of recent antibiotic use. [10] An alternate choice for oral antibiotic coverage may be necessary if the patient is allergic to penicillin.

      • If a patient with pneumococcal bacteremia is febrile or ill appearing on follow-up, the treatment should include a complete evaluation with LP, parenteral antibiotics, and hospitalization pending culture sensitivities. Serious bacterial infection (eg, meningitis) and pneumococcus resistant to third-generation cephalosporins are concerns; thus, hospitalization and close monitoring are recommended, with adjustment of antibiotic coverage as indicated by sensitivities and clinical course. [1, 6, 10]

    • Salmonella: Patients with Salmonella bacteremia should be treated with a course of antibiotics and appropriately monitored. Appropriate therapy depends on the clinical situation; patients who are ill appearing, febrile, younger than 3 months, or immunocompromised should receive a full sepsis evaluation and parenteral antibiotics, whereas immunocompetent afebrile children aged 3-36 months may be treated with a course of oral antibiotics. [1]

    • N meningitidis: As many as 50% of children who develop meningococcal disease are evaluated 2-3 days before the diagnosis and are treated on an outpatient basis for FWS. [1] Meningococcal disease has a high rate of occult presentation, and meningococcal bacteremia has a high potential morbidity and mortality rate because of focal complications such as meningitis, shock, and extremity necrosis. Treatment in patients with meningococcal bacteremia, regardless of clinical appearance, should involve a full sepsis evaluation, parenteral antibiotics, and hospitalization. [1, 6]

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Further Inpatient Care

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  • Hospitalization

    • Neonates younger than 1 month: Most guidelines recommend hospitalization, with or without antibiotic therapy, for all febrile infants younger than 1 month pending culture results. [10, 14]

    • Infants aged 1-3 months: Most guidelines recommend hospitalization for infants in this age group who do not meet low-risk criteria (ie, they are ill-appearing, appear toxic, are hypotensive, or were not previously healthy or they have a focal infection, high-risk petechiae, UTI, or WBC count per HPF of < 5 or >15). Infants who need supportive care such as oxygen and intravenous fluids should also be treated as inpatients, as well as those who cannot be treated as outpatients because of caregiver, transportation, communication, or other logistics. [10, 15] Outpatients whose blood or CSF cultures are positive for known bacterial pathogens should be readmitted for intravenous antibiotic therapy. [10]

    • Children aged 3-36 months: Infants and young children in this age group should be hospitalized if sepsis is a concern because of toxic appearance, unstable vital signs, or high-risk petechiae upon examination. They may also be admitted if they cannot be treated as outpatients because of caregiver, transportation, communication, or other logistics. [10, 15] Many infants and young children in this age group are initially treated as outpatients. They may need to be admitted if a blood culture is positive for known pathogens, depending on the clinical status of the patient and the specific organism grown (see Further Outpatient Care).

  • Tailored antibiotic therapy

    • Although this article focuses on the management of bacteremia caused by S pneumoniae, which is the most common isolated organism, occult bacteremia can be caused by rare pathogens, such as Enterobacteriaceae species and S aureus, which are not optimally covered by most common empiric antibiotics. As microbiologic laboratory data become available, antibiotic coverage may be tailored for improved coverage against specific organisms. Carbapenems, vancomycin, and cefepime should be considered when pathogens that are resistant to other antibiotics are recovered or suspected. Although these antibiotics have not been studied or suggested as empiric coverage in patients with FWS, they may be very useful when tailoring antibiotic treatment.

    • Microbiology, antibiotic coverage, and the clinical situation should be considered together when tailoring antibiotic therapy. A full discussion of focal infections and treatment approaches to rare pathogens is beyond the scope of this article, but 2 important situations warrant mention. First, vancomycin should be added upon clinical concern for meningitis to cover possible penicillin-resistant and ceftriaxone-resistant gram-positive organisms. Second, any infant or child with occult S aureus bacteremia should have an evaluation for a likely underlying source of infection, such as osteomyelitis or endocarditis, and should be covered with vancomycin or nafcillin.

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Inpatient & Outpatient Medications

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  • Amoxicillin, ampicillin, ceftriaxone, cefotaxime (See Medication.)

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Transfer

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  • Transfer is not likely unless complications such as sepsis or focal infections are present.

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Deterrence/Prevention

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  • Secondary prevention: Early identification of outpatients by screening and empiric antibiotic treatment of febrile infants and young children at risk for occult bacteremia is a form of secondary prevention. This approach does not prevent bacteria from entering the bloodstream in the first place, but it does prevent subsequent focal bacterial illness, morbidity, and mortality. [12]

  • Judicious antibiotic use: Approximately 30% of children with invasive pneumococcal infections received antibiotic treatment in the month before the infection, and children who have received antibiotics within the last month are at increased risk for invasive pneumococcal disease with antibiotic-resistant strains. [29] This suggests that judicious use of antibiotics for upper respiratory infections, bronchitis, acute otitis media, and sinusitis can prevent pneumococcal infections by decreasing the antibiotic pressure that selects for invasive and resistant pneumococcal strains.

  • Recent history

    • Widespread use of the conjugate Hib vaccine in the early 1990s is a recent example of the potential effects of vaccines as primary prevention. Before this vaccine, invasive Hib disease accounted for 10% of occult bacteremia in children aged 3-36 months; children with untreated bacteremia had approximately 20% risk for persistent bacteremia and as much as 15% risk for important focal infections such as meningitis. [6, 10, 12, 32]

    • Introduction of the vaccine decreased the incidence of invasive Hib disease by 90% shortly after its widespread use. [2, 11] Use of the vaccine has now essentially eliminated Hib as a cause of invasive disease in immunized children. [24] This success story serves as not only an example of prevention in occult bacteremia, but also (the authors hope) a roadmap for expectations following widespread use of the conjugate 7-valent pneumococcal vaccine.

  • S pneumoniae vaccine

    • The 7-valent conjugate pneumococcal vaccine was designed to cover 98% of the strains of S pneumoniae responsible for occult bacteremia. A multicenter surveillance found that isolates that are contained in the 7-valent conjugate pneumococcal vaccine cause 82-94% of S pneumoniae invasive disease. [29] See Causes.

    • Results of initial efficacy studies of the 7-valent pneumococcal vaccine are encouraging. Published reports of the phase II US trials in 37,000 children found that that the vaccine was 97% effective for vaccine-associated strains in fully vaccinated children and 89% effective overall. [2, 30] A study of the efficacy of this vaccine during the first year of its licensure indicates that 34-58% of children received at least one dose of vaccine and 14-16% of children were fully vaccinated; a 58-87% reduction in invasive pneumococcal disease occurred. [28] Further studies have reinforced these findings over the last decade. [49, 50, 51, 52]

    • More recent studies have highlighted a dampening in the overall rate of decline in invasive pneumococcal disease, with a rise in nonvaccine serotypes in some age groups. [52, 53, 54] These findings have confirmed concerns by some authors that reducing nasopharyngeal carriage of the vaccine serotypes may leave an ecologic niche that invasive serotypes not included in the vaccine may fill. [2] Early studies in the United States and a study in East Africa using a 5-valent conjugate pneumococcal vaccine revealed evidence of serotype replacement in nasopharyngeal carriage. [2, 85] However, the connection between colonization and virulence is not necessarily direct. No evidence indicates that nonvaccine strains in vaccinated children increase the rates of invasive disease. [2, 28]

    • Some authors are also concerned that use of the conjugate pneumococcal vaccine may alter antibiotic resistance patterns. Early studies show that the most common serogroups associated with penicillin resistance were all included in the 7-valent vaccine. [29] Strain 19A had become important in recent years because it is a nonvaccine strain with high antibiotic resistance that has been found in a large percentage of recent pneumococcal isolates. [53] The release of the 13-valent vaccine, which includes 19A, is expected to bring this serotype back under control.

    • Although the indications and dosing schedule for the conjugate pneumococcal vaccine are a separate topic and not fully addressed here, evidence suggests that the vaccine should be administered to all children younger than 5 years and priority should be given to children with underlying illnesses because of increased risk of morbidity and mortality associated with invasive pneumococcal infections. [29]

    • The release of the 13-valent pneumococcal conjugate vaccine in 2010, which includes serotype 19A along with 1, 3, 5, 6A and 7F, is likely to decrease the serotype replacement phenomenon and further reduce invasive pneumococcal disease. PCV13 should replace the remaining doses of PCV7 for partially immunized children and be given as an additional fifth dose for children who have received 4 PCV7 doses. [86]

  • N Meningitidis vaccine

    • The conjugated multivalent polysaccharide vaccine to strains A, C, Y and W-135 of N meningitidis has had success in Europe and Canada and was approved for use in the United States in 2005.

    • The vaccine is currently approved for use in children as young as 9 months with certain risk factors (eg, terminal complement deficiency, asplenia

    • A vaccine for the group B strain of the bacteria is undergoing clinical trials.

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Complications

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  • Complications of bacteremia (see Mortality/Morbidity)

    • Occult bacteremia results in morbidity and mortality due to focal infections that arise following the initial bloodstream infection. Most episodes of occult bacteremia spontaneously resolve, and serious sequelae are increasingly uncommon. However, serious bacterial infections occur, including pneumonia, septic arthritis, osteomyelitis, cellulitis, meningitis, and sepsis; death may result. [1, 5]

    • Of all focal infections that develop because of pneumococcal bacteremia, pneumococcal meningitis carries the highest risk for significant morbidity and mortality, including a 25-30% risk of neurologic sequelae such as deafness, mental retardation, seizures, and paralysis. [1, 2]

  • Complications of hospitalization

    • In addition to complications associated with bacteremia and its sequelae, numerous possible complications are associated with evaluation and empiric treatment of infants and young children at risk for occult bacteremia.

    • A study of hospitalized febrile infants younger than 2 months found that complications were common, many complications were preventable, and most infants were hospitalized longer than necessary. [87] In this study, 20% of all admissions resulted in at least one complication, and 60% of these complications were believed to be preventable (eg, medications overdose, fluid overload, intravenous infiltrate, intravenous skin sloughing, a kidnapped infant [a preventable complication of hospitalization in general, unrelated to the reason for admission], culture contamination that required follow-up). Of the infants in this study who were evaluated and found not to have bacterial disease based on cultures negative for known bacterial pathogens, 98% were hospitalized longer than 72 hours.

    • The risk of complications should be considered when weighing the risks and benefits of evaluation and empiric treatment of febrile infants and young children at risk for occult bacteremia and its sequelae. Because the overall risk of occult bacteremia decreases with widespread use of the conjugate pneumococcal vaccine, this balance between risk and benefit may need to be reevaluated.

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Prognosis

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  • Most episodes of occult bacteremia spontaneously resolve, and serious sequelae are increasingly uncommon. However, serious bacterial infections occur, including pneumonia, septic arthritis, osteomyelitis, cellulitis, meningitis, and sepsis; death may result. [1, 5]

  • Evaluation, treatment, and follow-up of febrile infants and young children at risk for occult bacteremia significantly decrease the risk for serious bacterial infections and sequelae.

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Patient Education

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