Changing spectrum of bacterial infections
The type of bacterial infections depends on the stage of the transplant, the use of prophylactic antibiotics, the presence of invasive devices, and the nature of bacterial colony.
During the first week after stem cell infusion, enteric gram negative bacterial infections are most common because of progressive mucositis and ongoing neutropenia. Of these, Pseudomonas species, E. coli and Klebsiella species are most common, all of which should respond to a combination of cephalosporin and aminoglycoside antibiotics except for multi-drug resistant Pseudomonas species.
Starting in the second week of the transplant, the incidence of gram positive bacterial infections increases. Generally, they are induced by Staphylococcus epidermidis and other skin flora, associated with the central venous catheter colonization.
Once patients recover from neutropenia, the risk of bacterial infections decreases until 2-3 months post-transplant when the level of opsonizing antibodies of IgG decreases below the threshold. In general, fever in a patient who is 1-3 months out from the transplant should be regarded as indication of either encapsulated bacterial infection or line associated bacterial infection. Most common encapsulated bacteria include Streptococcus pneumoniae, Hemophilus influenzae, Klebsiella pneumoniae, and Neisseria meningitides. Line associated bacteria may include both gram positive and gram negative organisms.
Persistent immunodeficiency induced by chronic graft versus host disease could also increase the risk of encapsulated bacterial infection.
Empiric management of febrile neutropenic patients
Since most patients receive broad-spectrum prophylactic antibiotics during the period of neutropenia, fever from a breakthrough bacterial infection indicates infections caused by drug resistant species. Although the relative risk of infection by either gram negative bacteria or gram positive bacteria would be the same during the first two weeks of neutropenia while on prophylactic antibiotics, the current guidelines emphasize empiric coverage for resistant gram negative bacteria before confirmation by cultures. It is based on several clinical studies that have shown a benign course of gram positive bacterial infection.
If patients continue to be febrile or show a new onset of fever after 2-3 days of no evidence of infection upon a changed spectrum of antibitotics for gram negative organisms, the gram negative coverage should be broadened to cover drug resistant Pseudomonas aeruginosa, Pseudomonas cepacia, Sternotrophomonas maltophilia, Proteus species, Acinetobacter species, Citrobacter species, Serratia species, or Enterobacter species. These organism can be covered by either imipenem or appropriate quinolone antibiotics. S. maltophilia is known to be more sensitive to minocycline and doxycycline.
If gram positive organisms are responsible for recurrent fever, it may indicate infections caused by Enterococcus species including vancomycin resistant Enterococcus, group D Streptococcus, non-hemolytic Streptococcus, Bacillus species, Corynebacterium species, or Lactobacillus species. Vancomycin si currently the drug of choice for these organisms, except for resistant Enterococcus species that requires other antibitotics such as Synercid (quinupristin/ dalfopristin).
Prophylaxis of Pneumocystis carinii and Toxoplasma gondii
Bactrim double strength 1 tablet bid on Mondays and Tuesdays has been used for the prophylaxis of infections by Pneumocystis carinii and Toxoplasmosis gondii. For prophylaxis of P. carinii infection in patients who are allergic or intolerant to sulfonamide, dapsone 100 mg daily with or without trimethoprim 5 mg/kg four times daily, inhalational pentamidine 300 mg per month, or atovaquone suspension 1500 mg daily may be used. Low dosage atovaquone (750 mg daily) has been associated with increase in P. carinii infection (J Infect Dis. 1999 Aug;180(2):369-76). For prophylaxis of toxoplasmosis in patients allergic to bactrim, pyrimethamine in a dosage of 50 mg daily or 50 mg three times a week with folinic acid 5-7.5 mg for each dose is recommended.
Therefore, combination of dapsone 100 mg daily with pyrimethamine 50 mg/folinic acid 7.5 mg 3 times weekly, or combination of inhalational pentamidine 300 mg per month with pyrimethamine 50 mg/folinic acid 7.5 mg 3 times weekly is recommended for patients who are allergic or intolerant to sulfonamide.
