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Sinusitis in the Immunocompromised, Diabetic, Cystic fibrosis, and HIV Infected Patients

Bacterial and fungal sinusitis occurs in a wide range of immunocompromised hosts, including those with neutropenia, diabetes mellitus, patients in critical care units (intubation, nasogastric tubes), cystic fibrosis, and patients infected with HIV, and may be acute or chronic. Although each group possesses a different risk attributed to their acquired immunodeficiency, early recognition, diagnosis, and treatment are paramount.

Sinusitis continues to be a potentially lethal and dreaded infectious complication of chemotherapy or bone marrow transplant-induced neutropenia. Recovery of the immune system is still the major prognostic factor in patients with this infection.


Predisposing factors

Absolute neutrophil counts (ANC) below 500 cells/mm3 strongly correlate with the development of invasive fungal disease in neutropenic patients. In bone marrow transplant patients, the critical time period for the development of fungal rhinosinusitis is approximately 3 weeks after transplantation. Secondary risk factors include 2 weeks or more of any of the following: systemic steroid use, ANC < 500 cells/ml, and exposure to multiple broad-spectrum antibiotics.

A number of factors may predispose the HIV-infected patient to sinonasal disease.   Qualitative and quantitative humoral immunity defects likely predispose HIV-infected patients to sinusitis. As in bone marrow transplant patients, mucociliary clearance abnormalities have been demonstrated in patients infected with HIV, particularly with CD4 counts < 300 cells/mm3. Ig-E mediated allergic disease is more prevalent in HIV-infected patients than in non-infected individuals and can cause mucosal edema and blockage of sinus ostia, resulting in a secondary bacterial infection. Nasopharyngeal lymphoid hypertrophy occurs in over half of patients in early HIV infection and decreases in size with immune system impairment. This local lymphoid hypertrophy may mechanically alter sinus drainage, predisposing to sinusitis.










The increased susceptibility of diabetic patients to infections including sinusitis is believed to be due to poor glucose control and the occurrence of hyperglycemia.  Hyperglycemia produces qualitative immune dysfunction through impairment of neutrophils. These include in vitro impairments in phagocytic function, granulocyte adherence, chemotaxis and bactericidal function. Hyperglycemia may also impair complement fixation and thereby decrease opsonization. 




Etiology


• Gram negative, and Gram positive bacteria and Fungi are the most common forms of infectious sinusitis in neutropenic patients. The bacterial isolates include Pseudomonas aeruginosa, Enterobacter spp., Escherichia coli, Serratia marcescens, Haemophilus influenzae, and Staphylococcus and Streptococcus spp. 


Aspergillus species are often the causative organisms of invasive fungal rhinosinusitis in the neutropenic host, although Mucor, Rhizopus, Alternaria species and other invasive molds have also been implicated.


• In patients with diabetes mellitus, fungi and S. aureus, streptococci and gram-negative enteric bacteria are the most common isolates. Aspergillus and Zygomycetes species are the most common causes of fungal sinusitis in this patient group, whereas Candida species are rarely reported.


• In patients with cystic fibrosis, Pseudomons aeruginosa is the most common cause of sinusitis. There appears to be an age related prevalence of  pathogens in both the lower and upper respiratory tracts. These include Haemophilus influenzae, Staphylococcus aureus, P. aeruginosa, Stenotrophomonas maltophilia, Achromobacter xylosoxidans, and Burkholderia cepacia complex.








• The organisms most commonly isolated in nosocomial sinusitis are gram-negative enteric bacteria (such as P. aeruginosa, Klebsiella pneumoniae, Enterobacteriaceae, Proteus mirabilis, and Serratia marcescens, streptococci, staphylococci, and anaerobic bacteria.


In general, the infecting organisms which cause sinusitis in the HIV-infected patient vary with the degree of immunosuppression. Sinusitis caused by opportunistic pathogens such as protozoa, fungi and atypical organisms usually occurs with a CD4 count less than 200 cells/mm3.The Causative Organisms in Patients with HIV Infection are:

• The same organisms seen in individuals without HIV.

• Aerobic bacteria (P. aeruginosa, Haemophillus influenzae, Klebsiella pneumoniae, Escerichia coli, Listeria monocytogenes, S. aureus, and Streptococcus spp.)

• Fungi ( Alternaria alternata, Aspergillus, Pseudallescheria boydii, Cryptococcus, Rhizopusand Candida albicans.)

• Parasites (Microsporidium, Cryptosporidium, and Acanthamoeba)

• Viruses (i.e., cytomegalovirus)

• Mycobacteria (atypical mycobacteria and Mycobacterium kansasii)

• Legionella pneumophila






Gram stain of Pseudomonas aeruginosa








Management


A successful outcome is contingent on both the recovery of immune function and early medical and surgical intervention. Effective glycemic control in diabetic patients improves multiple factors important in the host response to sinusitis.



The administration of growth factors also plays a role in the treatment of neutropenic patients with fungal rhinosinusitis. Patients who respond to granulocyte colony-stimulating factor (G-CSF) are more likely to have a favorable outcome. Granulocyte transfusions have also been used in invasive fungal rhinosinusitis to enhance immune status and bridge the interval until hematopoietic regeneration occurs. 


The choice of antimicrobials and antifungals effective against the organism causing sinusitis in the immunocompromised should be individualized as the microbiology varies from patient to patient. Empirical broad-spectrum coverage with a combination of a penicillin and a beta-lactamase inhibitor, plus an antimicrobial effective against aerobic gram-negative rods (i.e., an aminoglycoside, ceftazidime, a quinolone in adults and/or an antifungal), or a carbapenem may be warranted initially. Failure to respond to therapy mandates surgical drainage for culture and biopsy.


Treatment of fungal sinusitis includes a combination of early and aggressive surgical debridement and high-dose amphotericin B. An azole (i.e., miconazole) could be administered to treat susceptible isolates.


Correction or improvement in the underlying pathology, such as removing nasal tubes, controlling diabetes, and augmenting the immune status, may also be helpful.





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