See [@Wingard2012a]
Apparently HRCT gives diagnosis of pneumonia about four days prior to chest x-ray. Infectious causes much less likely in those not receiving chemotherapy, newly diagnosed patients and those post-treatment or post-transplant without GVHD. In newly diagnosed AML pulmonary infiltrates are generally not infectious and pre-treatment aspergillus is rare. Those patients undergoing chemotherapy or otherwise immunocompromised, infections are usually the cause of nodular lesions and bacteria are the leading cause. Diagnostic yields are highest when performed at initial presentation, i.e., bronchoscopy within 24 hours of presentation. Realize that patients may clinically, and most certainly radiographically, deteriorate during early therapy (first week or two) but that this clinical deterioration may be accompanied by microbiologic improvement. If GM was positive initially, serial monitoring may be helpful in determining response.
- viral disease
- P. jiroveci
- Legionella
- Mycoplasma
Mass lesions larger than 3cm more likely to be malignant, while those smaller than 1cm are generally not malignant. PET not sensitive enough for nodules < 1cm. Realize that halo sign is not specific for aspergillus. Likewise, the "reverse halo" is not specific for mucor.
- Bacterial agents
- i.e., gram positive and negative organisms
- earlier after SCT
- Nocardia
- later after SCT
- Aspergillus
- generally after at least two weeks of profound neutropenia
- about 1/2 nodules due to fungus and 80% of those due to aspergillus
- particularly in AML
-
90% with nodule >1cm, 80% with multiple nodules, 60% bilateral, 60% with halo sign, 30% consolidation
- usually peripheral locations
- flavus may be more common in hematologic malignancies than other species, particularly in AML and ALL [@Steinbach2012]
- lung is most common site of presentation for aspegillus (76% lung only) [@Steinbach2012]
- Worse survival if neutropenic at time of diagnosis of invasive aspergillus [@Steinbach2012]
- median time to diagnosis after HSCT is 97 days (similar to TRANSNET) [@Steinbach2012]
- P. jiroveci
- other molds
- at least one study found pleural effusion more likely with mucor than with aspergillus
- Toxoplasma
- Strongyloides
- chronic, inactive granulomata (Mtb, endemic/dimorphic fungi)
- considered mixed infections as well.
Need to place in references specific for this, all taken from [@Wingard2012a].
Sensitivity and specificity are >80% when used serially, 2x/week in those at risk of disease. Not so good when used once when have findings on radiography. Can be positive for penicillium and endemic fungi infections. Use of fungal prophylaxis attenuates usefulness of test. Bronchoalveolar lavage GM may increase yield over cultures alone.
As sensitive but not specific for aspergillus as many fungi release beta-glucan including candida, fusarium, trichosporon and pneumocystis.
Risk factors include:
- ATG induction
- Cord blood transplant
- Unmatched donor/recipient transplants
- GVHD
- T cell depleted stem cell transplants
Increasing number of risk factors increases risk. Most likely to see 6--12 months post-transplant.
Recent single center review by Marr and associates at Hopkins [@Neofytos2013] again demonstrates that HSCT patients are at the highest risk of disease and the greatest risk of death (52%). For the SOT, lung has the highest incidence (49/1000 person-years) and liver has the greatest mortality at 47%, approximating HSCT.
Includes stem cell, cord/double cord transplants. [@Winston2011] Initiate posaconazole 400mg PO BID from day 1 to day 100 post-transplant (day +1--+100) or until off of prednisone for GVHD prophylaxis. Ensure take with acidic drink. 2013 outpatient guidelines suggest if risk is 6--10% then to use fungal prophylaxis [@Flowers2013].
PCP prophylaxis should be considered in regimens with a risk of >3.5% i.e., purine analog-based regimens or >=20mg prednisone daily for at least a month [@Flowers2013]. These are essentially patients undergoing HSCT or induction therapy for leukemia and rhabdosarcoma.
Some taken during reading of [@Luong2010a], need to review [@Fischer2009] for more, plus add the NTM stuff. For now looks like the American Journal of Transplantation December 2009 Supplement 4 is all about screening.
Pre-transplant isolation does increase the risk of post-transplant recurrence. Some studies have found same strain is commonly found post-transplant [@RefWorks:2938], while others have not found this to be the case (need reference). No benefit shown (yet) of pre-transplant sinus surgery at reducing post-transplant recurrence, however post-transplant surgery combined with excellent nasal hygiene was of benefit in reducing BOS and reinfection/colonization [@Vital2012a]. MDR/pan-resistant organism does not preclude transplantation. One study at Toronto and Duke from patients CF transplanted from 1992--2001 did show decreased one and three year survival [@RefWorks:2926], but UNOS data shows no significant difference.
Several genomovars of B. cepacia, with III cenocepacia and II multivorans being the most frequently isolated. In CF patients, survival was worse at one year in those with post-transplant cencepacia (29%) as compared with other genomovars (89%) [@Alexander2008a; Boussaud2008]. But given nature of the studies, can really only just recommend caution in transplanting those with cenocepacia.
Only abscessus abscessus is of concern. Have plenty of literature on this and can add later.
Not much of a concern pre-transplant unless is a aspergilloma, which them would be removed at the time of surgery. Typically suggest 4--6 months of pre-transplant therapy with an effective drug. Is there anything on pre-transplant pulmonary aspergillosis that is not colonization? [@Singh2013] found in a small multicenter observational study that the median time after lung transplantation for invasive aspergillosis was 423 days. 53% of the patients had nodular disease, which was associated with better outcomes. Non-nodular disease associated with renal failure, CMV infection and prior vori prophylaxis. Successful outcome in 64% and 75% survival overall. But 12 week all-cause mortality 23% in nodular, 54% non-nodular.
If S. prolificans may have concern given propensity to cause invasive disease and difficulty in treating it.
Preventative/preemptive therapy should be considered for those who have anticipated duration of neutropenia, ANC <100, of >6 days in association with other risk factors such as severe mucositis [@Flowers2013]. Table 2 in Flowers, et. al., 2013 has expected febrile neutropenia rates for different diagnoses. Table 4 has other exclusion criteria for outpatient management. Empiric therapy should be fluoroquinolone plus amox/clav (or clinda if PCN allergy). Protection against HBV reactivation should be initiated with 3TC for those at risk and protection against herpes viruses should be considered in HSCT and leukemia patients (not lymphoma or solid organ based on a Cochrane review). Initial evaluation and management of neutropenic fever be as inpatient and monitored for at least four hours after initiation of IV antibiotics. MASCC score >20 or Talcott group 4 can be managed as outpatients. As additional precautions they do not recommend a neutropenic diet nor masks.