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By Carol A. Kemper, MD, FACP, Section Editor: Updates, Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases; Santa Clara Valley Medical Center, is Associate Editor for Infectious Disease Alert.
XDR gone TOTALLY Resistant?
Source: ProMED-mail alert January 13, 2012; promedmail.org
Following reports of the discovery of a strain of totally-drug resistant M. tuberculosis (TDR-TB) infecting 4 individuals in a Mumbai Hospital this month, another hospital in Bangalore may have identified two additional patients infected with an equally resistant strain of MTb. And the scary news is that one of the two patients seems to have gone AWOL and has not been seen for 2 weeks. Totally-drug resistant strains of MTb do not respond to any recognized antimycobacterial agent.
The two patients were being cared for at the Rajiv Ghandi Institute for Chest Disease (RGICD) in Bangalore, a public hospital that provides care for patients with active MTb, including those with resistant MTb. The patients are a 29-year old woman and a 56-year old man, and were initially receiving treatment for MDR-TB. After failing to respond to 8 months of initial therapy, their sputum culture results indicated the development of XDR-TB (eXtremely drug resistant version of the organism, which means they had developed resistance to at least 3 classes of antimycobacterial drugs). Both have now been treated for approximately 2.5 years, and both show evidence of ongoing treatment failure. Conflicting reports from the RGICD suggest that sputum cultures from both are now consistent with a totally-drug resistant strain, although specialized microbiologic susceptibility testing has not yet been performed.
Even worse, the RGICD failed to notify authorities regarding their findings and that the patient, who remains infectious, was missing. Sounds like India needs to tighten up their public health policies.
Aspergillosis in the ICU patient
Source: Hsu JL, et al. Diagnosing invasive fungal disease in critically ill patients. Critical Rev Micro 2011; 37(4):277-312.
Twice in the past year, I've been asked to evaluate the clinical significance of a positive sputum or endotracheal specimen for Aspergillus spp. in a critically ill non-immunocompromised cardiac surgery patient in the ICU. Both patients grew scant amounts of Aspergillus fumigatus from two or more respiratory specimens in the absence of any recognized malignancy or immunosuppression. Neither was a candidate for endobronchoscopic lung biopsy at the time of consultation, which may have been helpful in determining the presence of invasive disease. Both had underlying COPD; one had been treated with a single dose of methylprednisolone; and the other (from China) had a positive gamma-interferon TB blood test, and evidence of old healed MTb on chest radiographs. How significant was this information?
This helpful review by Hsu and colleagues examines the host and risk factors, and clinical and radiographic findings in patients with invasive fungal disease (IFD) in the ICU setting. Because diagnostic techniques are often inadequate at confirming IFD in critically ill patients in the absence of histopathologic data demonstrating invasive disease, the diagnosis can be problematic. Available serologic studies provide poor test performance, a high frequency of false-positives, and delayed results.
An awareness of risk factors and host factors is important. Beyond the usual overt immunosuppression, risk factors include corticosteroids, indwelling central venous catheters, the use of prolonged antibiotics and total parenteral nutrition, breakdown of mucosal surfaces, and renal failure. Certain groups of non-immunocompromised patients are also at increased risk for fungal infection, including patients with a history of COPD, bronchiectasis, previous pulmonary tuberculosis, and cirrhosis. Among 89 ICU patients without malignancy diagnosed with invasive aspergillosis, 42% had COPD and 7% had cirrhosis. Another study found that, among 65 COPD patients diagnosed with invasive aspergillosis, the mean forced expiratory volume was 39% of predicted (consistent with severe disease), the mean corticosteroid use was 24 mg per day, and the mortality was 91%.
The authors advocate a "diagnosis centered approach" including prompt CT scanning and bronchoalveolar lavage (including BAL-b-D-glucan testing), and the use of CT-guided percutaneous lung biopsy in non-mechanically ventilated patients whenever possible. As many specimens as possible should be submitted to the lab for respiratory culture, blood fungal culture, and non-culture techniques, such as galactomannin and b-D-glucan [This should b as in "Beta" symbol.] testing of blood; Cryptococcal antigen of blood is relatively easy and reliable.
Radiographically, fungal lung infection may present differently in non-immunosuppressed patients compared with those with immunosuppression. For example, in one survey of critically ill patients without malignancy diagnosed with invasive aspergillosis, only 17% exhibited the "classic" halo sign; other radiographic findings such as bronchpenumonia, atelectasis and pleural effusion were more common. In another survey, only 6% of COPD patients without malignancy with invasive aspergillosis exhibited a halo sign. More commonly such patients with IFA may exhibit bronchopneumonia, centrilobular nodularity, a "tree-in-bud" pattern, peribronchial changes, or ground glass attenuation. The typically angioinvasive disease, with macronodules > 1 cm are not as likely to occur, as the disease typically begins with a respiratory portal of entry.