A Retrospective Characterization of Dexmedetomidine-Suspected Fever and Its Consequences in Adult Critically Ill Patients.

BACKGROUND: Current evidence for dexmedetomidine-suspected fever (DSF) is limited. Lack of recognition may lead to costly or potentially harmful interventions for critically ill patients. OBJECTIVE: The primary objective was to characterize escalations of care related to DSF. Secondary objectives were to describe the incidence, severity, and consequences associated with DSF. METHODS: A retrospective review was conducted in critically ill adults who developed fever ≥39°C within 12 h from initiation of dexmedetomidine, with resolution of fever to <39°C within 12 h after discontinuation. The primary outcome was percentage of patients who received an escalation of care due to fever. Secondary outcomes included the percentage of patients who developed a multidrug-resistant organism or Clostridium difficile infection. RESULTS: Eighteen of 3943 patients screened in 4099 encounters met criteria for DSF (0.4%). The majority were white (83.3%), male (66.7%), and underwent cardiac surgery (61.1%). Median (interquartile range [IQR]) time to fever onset and resolution were 5.5 (3.6-7.6) and 1.3 (1.0-2.9) h. Nine patients (50%) underwent infectious workup including antimicrobial initiation (n = 1, 5.6%), broadening of antimicrobials (n = 4, 22.2%), or culture collection (n = 9, 50%). Eleven patients (61.1%) underwent attempted temperature reduction. Twelve patients (66.7%) underwent diagnostic imaging. Incidence of multidrug-resistant organism and C. difficile infection were low (11.1 and 16.7% of fever patients, respectively). CONCLUSION AND RELEVANCE: Incidence of DSF was low and more common in cardiac surgery patients. Unrecognized DSF led to an escalation of care in most patients. Dexmedetomidine exposure should be considered as a potential cause of fever in critically ill adults.

Nasopharyngeal viral PCR in immunosuppressed patients and its association with virus detection in bronchoalveolar lavage by PCR.

BACKGROUND AND OBJECTIVE: Pulmonary infiltrates are common in immunosuppressed patients. Bronchoscopy with bronchoalveolar lavage (BAL) is often used to evaluate their aetiology. However, it may not always be easily performed. Thus, alternative diagnostic strategies may be needed. There is limited data on the correlation of nasopharyngeal (NP) respiratory viral panel (RVP)-PCR testing compared with BAL. We aimed to identify the predictive value of NP RVP-PCR samples compared with samples obtained from BAL in immunosuppressed patients with pulmonary infiltrates. METHODS: We conducted an observational retrospective study of immunosuppressed adults who underwent bronchoscopy in the Pulmonary Department at the University of Rochester Medical Center between January 2011 and June 2016. We compared the positive and negative predictive values, sensitivity, specificity and false negative rate of NP RVP-PCR and BAL RVP-PCR, as well as identified clinical predictors of positive viral BAL RVP-PCR. RESULTS: Eighty-nine immunosuppressed patients had both NP and bronchoalveolar RVP-PCR testing. Twenty-one patients had NP(+)BAL(+) RVP-PCR testing. Seven patients had false negative (NP(-)BAL(+)) RVP-PCR testing. Three patients had NP(+)BAL(-) RVP-PCR testing. The positive and negative predictive values of NP RVP-PCR testing were 88% and 89%, respectively. Allogeneic bone marrow transplantation and testing performed in the winter and spring months were significantly associated with positive BAL RVP-PCR (OR = 3.3 (1.19-9.12); OR = 4.62 (1.64-12.99), respectively). CONCLUSION: NP RVP-PCR testing has high concordance with testing performed on BAL samples. Repeat testing through BAL is beneficial when there is high concern for viral infection after initial NP RVP-PCR testing is negative.

Achieving high treatment success for multidrug-resistant TB in Africa: initiation and scale-up of MDR TB care in Ethiopia--an observational cohort study.

BACKGROUND: In Africa, fewer than half of patients receiving therapy for multidrug-resistant TB (MDR TB) are successfully treated, with poor outcomes reported for HIV-coinfected patients. METHODS: A standardised second-line drug (SLD) regimen was used in a non-governmental organisation-Ministry of Health (NGO-MOH) collaborative community and hospital-based programme in Ethiopia that included intensive side effect monitoring, adherence strategies and nutritional supplementation. Clinical outcomes for patients with at least 24 months of follow-up were reviewed and predictors of treatment failure or death were evaluated by Cox proportional hazards models. RESULTS: From February 2009 to December 2014, 1044 patients were initiated on SLD. 612 patients with confirmed or presumed MDR TB had ≥ 24 months of follow-up, 551 (90.0%) were confirmed and 61 (10.0%) were suspected MDR TB cases. 603 (98.5%) had prior TB treatment, 133 (21.7%) were HIV coinfected and median body mass index (BMI) was 16.6. Composite treatment success was 78.6% with 396 (64.7%) cured, 85 (13.9%) who completed treatment, 10 (1.6%) who failed, 85 (13.9%) who died and 36 (5.9%) who were lost to follow-up. HIV coinfection (adjusted HR (AHR): 2.60, p<0.001), BMI (AHR 0.88/kg/m(2), p=0.006) and cor pulmonale (AHR 3.61, p=0.003) and confirmed MDR TB (AHR 0.50, p=0.026) were predictive of treatment failure or death. CONCLUSIONS: We report from Ethiopia the highest MDR TB treatment success outcomes so far achieved in Africa, in a setting with severe resource constraints and patients with advanced disease. Intensive treatment of adverse effects, nutritional supplementation, adherence interventions and NGO-MOH collaboration were key strategies contributing to success. We argue these approaches should be routinely incorporated into programmes.

Excess deaths associated with tigecycline after approval based on noninferiority trials.

BACKGROUND: On the basis of noninferiority trials, tigecycline received Food and Drug Administration (FDA) approval in 2005. In 2010, the FDA warned in a safety communication that tigecycline was associated with an increased risk of death. METHODS: PubMed, EMBASE, Scopus, and ClinicalTrials.gov were searched using the terms "tigecycline" and "randomized controlled trial (RCT)" through April 2011. Excess deaths and noncure rates for both approved and nonapproved indications were examined using meta-analysis. RESULTS: Ten published and 3 unpublished studies met inclusion criteria (N = 7434). No significant heterogeneity was seen for mortality (I(2 )= 0%; P = .99) or noncure rates (I(2 )= 25%; P = .19). Across randomized controlled trials, tigecycline was associated with increased mortality (risk difference [RD], 0.7%; 95% confidence interval [CI], 0.1%-1.2%; P = .01) and noncure rates (RD, 2.9%; 95% CI, 0.6%-5.2%; P = .01). Effects were not isolated to type of infection or comparator antibiotic regimen, and the impact on survival remained significant when limited to trials of approved indications (I(2 )= 0%; RD, 0.6%; P = .04). A pooled analysis of the 5 trials completed by early 2005 before tigecycline was approved would have demonstrated a similar harmful effect of tigecycline on survival (I(2 )= 0%; RD, 0.7%; P = .06). CONCLUSIONS: Pooling noninferiority studies to examine survival may help ensure the safety and efficacy of new antibiotics. The association of tigecycline with excess deaths and noncure includes indications for which it is approved and marketed. Tigecycline cannot be relied on in serious infections.

"If the glove fits": Hospital-wide universal gloving is associated with improved hand hygiene and may reduce Clostridioides difficile infection.

OBJECTIVE: To determine whether a hospital-wide universal gloving program resulted in increased hand hygiene compliance and reduced inpatient Clostridioides difficile infection (CDI) rates. DESIGN: We carried out a multiple-year before-and-after quasi-experimental quality improvement study. Gloving and hand hygiene compliance data as well as hospital-acquired infection rates were prospectively collected from January 1, 2015, to December 31, 2017, by secret monitors. SETTINGS: The University of Rochester Strong Memorial Hospital, an 849-bed quaternary-care teaching hospital. PATIENTS: All adult inpatients with the exception of patients in the obstetrics unit. INTERVENTIONS: A hospital-wide universal gloving protocol was initiated on January 1, 2016. RESULTS: Hand hygiene compliance increased from 68% in 2015 reaching an average of 88% by 2017 (P < .0002). A 10% increase in gloving per unit was associated with a 1.13-fold increase in the odds of hand hygiene (95% credible interval, 1.12-1.14). The rates of CDI decreased from 1.05 infections per 1,000 patient days in 2015 to 0.74 in 2017 (P < .04). CONCLUSION: A universal gloving initiative was associated with a statistically significant increase in both gloving and hand hygiene compliance. CDI rates decreased during this intervention.

Chronic therapeutic anticoagulation is associated with decreased thrombotic complications in SARS-CoV-2 infection.

BACKGROUND: Thrombotic disease complicates severe SARS-CoV-2 infection and is associated with increased morbidity and mortality. Various anticoagulation strategies have been evaluated in hospitalized patients to prevent complications. The impact of chronic anticoagulation before SARS-CoV-2 infection on the risk for subsequent thrombosis has not been systematically studied. METHODS: This was a retrospective single-center study. All patients with positive SARS-CoV-2 PCR testing from March 13, 2020, through May 6, 2020, at the University of Rochester Medical Center were identified. We included all patients receiving therapeutic anticoagulation for at least 1 month before COVID diagnosis. We documented the rate of thrombotic complications, type of anticoagulation, bleeding complications, and mortality. RESULTS: A total of 107 SARS-CoV2-infected patients were chronically anticoagulated before SARS-CoV-2 testing with a median age of 78. Of those, 42 required hospital admission, with 17 requiring intensive care. No patients, inpatient or outpatient, were diagnosed with a new symptomatic thrombotic complication. Three patients had minor bleeding in the hospital. Thirteen (12%) patients died (69% male). CONCLUSION: Our uncontrolled findings suggest that chronic anticoagulation at the time of infection may protect against thrombotic complications and decrease disease severity.

Probable Donor-Derived Human Adenovirus Type 34 Infection in 2 Kidney Transplant Recipients From the Same Donor.

Human adenovirus type 34 (HAdV-34) infection is a recognized cause of transplant-associated hemorrhagic cystitis and, in rare cases, tubulointerstitial nephritis. The source of such infections is often difficult to assess, that is, whether acquired as a primary infection, exposure to a pathogen in the transplanted organ, or reactivation of an endogenous latent infection. We present here 2 cases of likely transplant-acquired HAdV-34 infection from the same organ donor, manifesting as tubulointerstitial nephritis in 1.

CNS Melioidosis in a Traveler Returning from Cabo, Mexico.

Melioidosis is caused by the gram-negative bacillus Burkholderia pseudomallei, endemic to northern Australia and Southeast Asia. We present a patient who traveled to Mexico, returned to the United States, and developed progressive manifestations of melioidosis, culminating as central nervous system disease. Standard therapy was contraindicated, and a prolonged intensive phase was employed.

The clinical impact of pneumocystis and viral PCR testing on bronchoalveolar lavage in immunosuppressed patients.

INTRODUCTION: Pulmonary infiltrates in immunosuppressed patients are common. Yields from bronchoscopy with bronchoalveolar lavage (BAL) has been reported to be between 31 and 65%. The clinical impact of pneumocystis and viral Polymerase chain reaction (PCR) testing on BAL has not been extensively evaluated in a mixed immunosuppressed patient population. METHODS: We performed a retrospective chart review of immunosuppressed adults with pulmonary infiltrates who underwent BAL at the University of Rochester Medical Center. Only one BAL per patient was included. We compared the rate of positive PCR testing to conventional testing. We then investigated factors associated with positive PCR testing. Finally, we assessed for changes in antimicrobial therapy after bronchoscopy. RESULTS: Three hundred and fifty-nine patients underwent BAL with 249 patients having pneumocystis PCR testing and 142 having viral PCR testing. Pneumocystis identification occurred in 43 patients and viral species identification occurred in 56 patients. PCR testing increased pneumocystis identification compared to microscopy, 14% vs. 5%, p = 0.01, and viral identification compared to culture, 25% vs. 6%, p = 0.0001. Of the patients with positive pneumocystis PCR testing 49% had antibiotics stopped, 66% were started on anti-pneumocystis therapy, and only 6% did not receive treatment. There was no difference in the number of patients with antibiotics stopped based on viral PCR testing results. DISCUSSION: PCR testing increases BAL yield in immunosuppressed patients compared to conventional testing. Pneumocystis identified by PCR only may cause a self-limited infection and may not require antimicrobial therapy. PCR testing should be included in the evaluation of pulmonary infiltrates in immunosuppressed patients.

Legionella micdadei: A Forgotten Etiology of Growing Cavitary Nodules: A Case Report and Literature Review.

Background. Legionella micdadei is a Gram negative bacterium that can stain weakly acid fast. It was first described in 1979 after immunosuppressed patients developed pneumonia at a Pittsburgh VA, initially given the name Pittsburgh Pneumonia Agent. It is the second most common Legionella species causing infection after pneumophila, and typically infects immunocompromised hosts. It is not easy to be cultured which makes diagnosing difficult. Case Presentation. A 31-year-old female with ulcerative colitis, primary sclerosing cholangitis, and cirrhosis presented with fever, chills, shortness of breath, dry cough, and chest pain for five days after being started on immunosuppression for autoimmune hepatitis two months earlier. The first chest CT showed small bilateral cavitary nodules. The nodules continued to grow on subsequent imaging despite what was thought to be appropriate therapy. A transthoracic biopsy was performed which grew Legionella micdadei and the patient improved after being treated with levofloxacin. Conclusion. Legionella micdadei is an atypical pathogen known to cause pneumonia in immunosuppressed patients. This case highlights a typical presentation of an atypical infection not commonly thought about and should be considered when nodules are growing despite being on broad antimicrobial therapy.

A case of Lemierre's syndrome with septic shock and complicated parapneumonic effusions requiring intrapleural fibrinolysis.

Lemierre's syndrome is a septic thrombophlebitis of the internal jugular vein, which can lead to severe systemic illness. We report a case of an otherwise healthy 26-year-old man who suffered from pharyngitis followed by septic shock requiring intubation and vasopressor support from Fusobacterium necrophorum bacteremia. The septic emboli to his lungs caused complicated bilateral parapneumonic effusions, which recurred after initial drainage. He required bilateral chest tubes and intrapleural tPA to successfully drain his effusions. His fever curve and overall condition improved with the resolution of his effusions and after a 33-day hospitalization, he recovered without significant disability. The severity of his illness and difficult to manage complicated parapneumonic effusions were the unique facets of this case. Using an evidence-based approach of tPA and DNase for complicated parapneumonic effusions in Lemierre's syndrome can be safe and effective.

Impact and cost of the serum galactomannan assay at a tertiary care facility.

BACKGROUND: Invasive aspergillosis carries a high mortality with a rising prevalence in immunocompromised hosts. Diagnosis of invasive aspergillosis is challenging and delays in treatment are associated with poor outcomes. The galactomannan assay (GM), a non-culture-based surrogate marker of fungal infection, is widely used in diagnosis. It is unknown whether this assay impacts clinical decision making. We evaluated whether GM testing results in earlier initiation of antifungal therapy and is cost effective. METHODS: We carried out a retrospective review of the electronic medical records of all patients undergoing GM at a 907-bed tertiary-care general hospital from July 11, 2011, to June 12, 2012. Records of patients with a positive GM were individually reviewed to determine the timing of the assay result, presence and timing of relevant culture data, whether BAL GM was performed, radiology data consistent with invasive aspergillosis, and the timing of initiation of antifungal therapy. For each case, it was determined whether GM results impacted the decision to initiate antifungal therapy. RESULTS: Forty-six nonduplicate GM samples were positive (>0.5) of 1419 performed. Results were considered to be false positives in 18 cases by care teams. In 21 cases, antifungal therapy was initiated before the assay result based on clinical suspicion, culture data, and/or radiology. The serum GM was performed 164 times at a cost of $21,789 for a single positive result effecting modification of patient care. CONCLUSION: Serum GM testing at a tertiary-care institution is commonly used but infrequently impacts clinical decision making with major financial burden.