16.2 Infections in the Immunocompromised Host, Tropical & Bioterror Infections

Febrile Neutropenia

Definition: a single temperature of 38.3 °C or more, or 38.0 °C sustained for an hour, with an absolute neutrophil count below 500/µL or expected to fall below it.

• Act within 1 hour: draw blood cultures from a peripheral site and each catheter lumen, then start an antipseudomonal beta-lactam (piperacillin-tazobactam, cefepime, meropenem, or imipenem).
• Add vancomycin only for an indication:
  • Suspected catheter-related infection.
  • Skin or soft tissue infection.
  • Pneumonia.
  • Hemodynamic instability.
  • Known colonization with resistant gram-positive organisms.
  • Severe mucositis in a patient on fluoroquinolone prophylaxis.
• Add antifungal therapy for persistent fever after about 4 to 7 days, or for a suggestive CT (nodules with halo signs), with an echinocandin or a mold-active azole.
• Think beyond bacteria: typhlitis (neutropenic enterocolitis), perirectal infection (avoid digital rectal examination and rectal thermometers), Clostridioides difficile, and viral reactivation.
• G-CSF is not routinely added to treat established fever, but is used in high-risk settings.
• Do not wait for neutrophil recovery before escalating in deteriorating patients; the inflammatory response is blunted, so physical findings are muted.

Transplant Recipients: Timeline Thinking

• Cytomegalovirus disease presents with fever, leukopenia and thrombocytopenia, pneumonitis, hepatitis, or colitis; diagnose by quantitative PCR with tissue biopsy for organ disease, and treat with IV ganciclovir (valganciclovir for less severe disease). Resistance is managed with foscarnet, cidofovir, or maribavir.
• Pneumocystis pneumonia presents with dry cough, progressive hypoxemia, and a markedly elevated LDH, with diffuse ground-glass opacity on CT. Treat with high-dose trimethoprim-sulfamethoxazole plus corticosteroids when PaO2 is below 70 mmHg or the alveolar-arterial gradient is above 35 mmHg.
• Invasive aspergillosis: nodules with halo and later air-crescent signs, serum and BAL galactomannan; treat with voriconazole or isavuconazole.
• Mucormycosis: diabetes with ketoacidosis, deferoxamine, or hematologic malignancy; rhino-orbital-cerebral or pulmonary disease with tissue necrosis. Treatment requires surgical debridement plus liposomal amphotericin B; mucorales are resistant to voriconazole.
• Asplenia: fulminant sepsis from encapsulated organisms (S. pneumoniae, H. influenzae, N. meningitidis), Capnocytophaga after dog bites, and severe babesiosis. Treat early and aggressively; vaccinate and educate.
• HIV with advanced immunosuppression: consider Pneumocystis, tuberculosis, cryptococcosis, toxoplasmosis, disseminated Mycobacterium avium complex, and CMV retinitis, as well as the usual bacterial pathogens.

Malaria, Babesiosis and Other Parasitic Emergencies

Severe Falciparum Malaria

• Criteria: impaired consciousness or coma, severe anemia, acidosis, hypoglycemia, kidney injury, pulmonary edema, shock, bleeding, parasitemia above about 10%, or jaundice with other organ dysfunction.
• Treatment: intravenous artesunate, which reduced mortality compared with quinine in large trials. Follow with a full oral course (artemether-lumefantrine). Watch for delayed post-artesunate hemolysis at 1 to 3 weeks, and check a hemoglobin weekly for a month.
• Supportive care: avoid overhydration (pulmonary edema is common), treat hypoglycemia, use kidney replacement therapy for acidosis and kidney failure, and transfuse for severe anemia. Exchange transfusion is no longer routinely recommended.
• Avoid corticosteroids in cerebral malaria.

Babesiosis

• Northeastern and upper midwestern United States; Ixodes ticks, which also transmit Lyme disease and anaplasmosis.
• Severe disease occurs with asplenia, age over 50, HIV, and immunosuppression: hemolytic anemia, jaundice, ARDS, and disseminated intravascular coagulation.
• Diagnosis: thin smear ring forms and "Maltese cross" tetrads, plus PCR.
• Treatment: azithromycin plus atovaquone for mild disease; clindamycin plus quinine with exchange transfusion for high parasitemia (above about 10%), severe hemolysis, or organ failure.

Strongyloides Hyperinfection

• Chronic autoinfection can persist for decades after exposure in endemic regions.
• Corticosteroids (and HTLV-1 infection) convert it to hyperinfection and dissemination: diffuse alveolar hemorrhage, ileus, and recurrent gram-negative bacteremia and meningitis from enteric organisms carried by migrating larvae.
• Diagnosis: larvae in stool, sputum, or BAL; serology before immunosuppression in at-risk patients.
• Treatment: ivermectin (parenteral or rectal routes are used when ileus prevents absorption), plus antibiotics for the bacteremia. Screen and treat before starting steroids in at-risk patients.

Other Travel-Related Causes

• Dengue: biphasic fever, severe myalgia, thrombocytopenia, plasma leakage with shock; supportive care with careful fluid titration.
• Typhoid: fever, abdominal pain, relative bradycardia; treat with ceftriaxone or azithromycin.
• Leptospirosis: freshwater exposure, conjunctival suffusion, jaundice with kidney failure (Weil disease), and pulmonary hemorrhage; treat with penicillin or ceftriaxone.
• Rickettsial disease: Rocky Mountain spotted fever with a centripetal rash, hyponatremia, and thrombocytopenia; doxycycline empirically, because delay is fatal. Scrub typhus and murine typhus follow the same rule.

Bioterrorism Agents

Varicella can mimic smallpox, but its lesions are asynchronous, centripetal, and spare the palms and soles. Notify public health authorities immediately for any suspected agent of bioterrorism.