Infectious Complications in Special Hosts

Pulmonary Symptoms

Bacterial pneumonia caused by S. pneumoniae is suspected in a patient with fever, cough, chest pain, sputum production (older patients), and abnormal chest radiograph (lobar infiltrate or other parenchymal or pleural abnormalities). Patients often appear toxic. Laboratory findings include leukocytosis, frequently with an increase in immature forms. In addition to other encapsulated bacteria, other causative agents of pneumonia include Mycoplasma pneumoniae and Chlamydophila pneumoniae , both of which have been shown to cause excessive morbidity in patients with sickle hemoglobinopathy.

Acute chest syndrome, described as fever and new pulmonary symptoms in a patient with Hb SS or Hb SC, commonly is precipitated by fat embolism and infection, usually community-acquired pneumonia. ^, Specific etiology can be difficult to differentiate. ^, Patients have chest pain, rales on auscultation, and infiltrates caused by focal vaso-occlusive necrosis or frank pulmonary infarction, although the latter may be less frequent in children. Radiographic abnormalities can be minimum during the first few days of symptoms. Precipitating infectious agents are bacteria, Chlamydophila , and viruses (especially influenza). ^, In contrast, primary vaso-occlusive crisis involving ribs can cause splinting, diminished pulmonary clearance, and secondary bacterial pneumonia.

Laboratory data helpful in differentiating bacterial infection from vaso-occlusive processes are increased band count and either extremely high or low white blood cell counts (>30,000 or <5000 cells/μL). Blood gas determinations in patients with acute pneumonia show oxygen desaturation, but patients with acute chest syndrome due to vaso-occlusion can also exhibit abnormal blood gases as a result of ventilation-perfusion mismatch. Patients with significant vaso-occlusive pulmonary disease require prompt transfusion or exchange transfusion.

Central Nervous System Symptoms

In 1971, Barrett-Connor calculated that children with Hb SS had a 300-fold higher risk for pneumococcal meningitis than unaffected children. Children with Hb SS in industrialized countries have a 6%–8% chance of experiencing bacterial meningitis, and those in Africa have a 19% risk. Of all children with Hb SS infected with S. pneumoniae in the pre-PCV era, meningitis developed in 20% of children, and, of those children, 15% died. Factors historically associated with death in children with Hb SS and Hb SC included age >4 years, S. pneumoniae serotype 19F, and not being followed by a hematologist. However, rates of invasive pneumococcal disease have declined by 93% by the use of prophylactic penicillin in young children with Hb SS, immunization with PCV7 and PCV13, and prompt use of antimicrobial agents for febrile illnesses. ^{, ,} Current rates of invasive pneumococcal infection in children in the US with Hb SS and fever probably are ≤4%.

Lumbar puncture should be performed immediately in all febrile children with Hb SS who appear ill. This practice is particularly important in infants whose mental status can be difficult to evaluate and in children who have received oral antibiotics that can mitigate or delay signs of serious infection. In children with Hb SS, the incidence of overt central nervous system (CNS) vaso-occlusive disease (stroke) has been reduced to ∼1%, and this condition typically manifests with neurologic abnormalities in the absence of signs of infection. The management of pneumococcal meningitis includes appropriate antimicrobial therapy and consideration of early adjunctive corticosteroid therapy in an attempt to decrease the CNS inflammatory response.

Bone and Joint Infections

Bone and joint infection frequently is associated with bone ischemia and can manifest as dactylitis (in infants), pyogenic arthritis, or osteomyelitis, with erythema, swelling, and pain. ^, An infectious cause sometimes is suggested by the clinical presentation (e.g., as a complication of septicemia due to S. pneumoniae or a subacute presentation with less systemic illness due to Salmonella ). A limp or refusal to bear weight may be the only clinical complaint. Bone and joint infections in Hb SS are associated most often with S. aureus , as in unaffected children. Salmonella spp., including serotypes associated specifically with bone and joint infections ( S. enterica [formerly choleraesuis ], S. heidelberg ), also are important because of splenic dysfunction, and can manifest either as systemic infection or with localized signs and symptoms. Blood and stool specimens, as well as aspirates from infected sites, should be obtained for cultures before empiric antibiotic therapy is begun. It is important to determine specific etiology and antimicrobial susceptibility because prolonged therapy generally is required.

Clinical differentiation between osteomyelitis and vaso-occlusive ischemia in the bone is difficult. Pain and tenderness out of proportion to physical findings, bilateral or symmetric involvement, and diffuse (as opposed to focal) symptoms over the diaphysis or the diaphysis and metaphysis of long bones (or dorsum of the hands and fingers in infants) may indicate infarction. Laboratory findings may be helpful. Elevated erythrocyte sedimentation rate (which, at baseline, is typically low in Hb SS) suggests bacterial infection, whereas leukocyte count and C-reactive protein level can be elevated during infarction. Bony destruction (“crumbling-bone disease”) and periosteal new bone formation visualized on plain radiograph can occur with either condition. Needle aspiration of involved bone, or open bone biopsy, often is necessary to establish a definite bacterial cause. Imaging studies can be useful in establishing an etiology, but differentiation of infarction from infection remains difficult in some cases ( Fig. 106.1 ). Magnetic resonance imaging (MRI) can identify a subperiosteal fluid collection that signifies osteomyelitis and can distinguish bone from muscle involvement. In addition, higher fat-saturated T1 signal intensity has been proposed as a sensitive finding in bone infarction. Ultrasound has been proposed as another helpful modality. However, definitive studies (e.g., prospective imaging and universal sampling for microbiologic confirmation) have not been performed. Radionuclide bone scanning is difficult to interpret in this context and is infrequently useful.

Meningitis, Septicemia, and Pneumonia

Infants and young children with Hb SS and fever should be evaluated and treated for presumed bacterial infection. Initial evaluation usually includes a complete blood cell count, blood culture, and chest radiograph, particularly in young children in whom the physical examination may not be optimal. Patients who are at high risk for infection (i.e., those who look ill and who have a body temperature >40°C or white blood cell count >30,000 or <5000 cells/μL) are more likely to have systemic bacterial infection and should be hospitalized for aggressive therapy. Children who have had previous episodes of pneumococcal BSIs are at increased risk for repeated infection and warrant special consideration.

Patients who are febrile but do not appear ill have been managed successfully in a variety of ways, including (1) observation in a short-stay area of the hospital for several hours after institution of antimicrobial therapy and (2) parenteral administration of ceftriaxone and close observation on an outpatient basis. Enthusiasm for the latter approach is tempered by case reports of severe and rapidly fatal immune-mediated hemolysis due to ceftriaxone in patients with Hb SS and in other patients who have received multiple courses of the drug. ^, All febrile children with Hb SS should be given an antibiotic. In the case of disease that is highly likely to be a vaso-occlusive crisis, therapy can be given orally with close follow-up.

S. pneumoniae that is nonsusceptible to penicillin or cephalosporins poses a particular challenge, ^{, ,} especially for children <3 years who are receiving penicillin prophylaxis. Most commonly, vancomycin, plus a third-generation cephalosporin, is considered presumptive therapy for BSI (i.e., pending culture and susceptibility results). Fluoroquinolones may be considered for therapy in developing countries where widespread antibiotic resistance is present. For meningitis, particularly when corticosteroids are used, vancomycin (60 mg/kg/day, up to 3600 mg/day), plus ceftriaxone, is given empirically.

If clinically indicated for treatment at the clinical site and the documented organism, newer agents with activity against resistant gram-positive organisms, including daptomycin, ceftaroline, or linezolid, can be considered, but no studies of these agents have been performed specifically in patients with sickle cell disease.

Bone and Joint Infections

Management for bone or joint infection includes surgical consultation for a specimen for culture and empiric use of agents effective against S. aureus (e.g., oxacillin, nafcillin, vancomycin) and Salmonella (e.g., third-generation cephalosporin or fluoroquinolone). Extensive disease, particularly that due to Salmonella spp., usually requires debridement and prolonged antimicrobial therapy (e.g., ≥6 months), as for chronic osteomyelitis.