Ciprofloxacin-Resistant Pseudomonas aeruginosa Lung Abscess Complicating COVID-19 Treated with the Novel Oral Fluoroquinolone Delafloxacin.

PURPOSE: We report the development of a lung abscess caused by a ciprofloxacin-resistant Pseudomonas aeruginosa in a patient with COVID-19 on long-term corticosteroid therapy. Successful antimicrobial treatment included the novel oral fluoroquinolone delafloxacin suggesting an oral administration option for ciprofloxacin-resistant Pseudomonas aeruginosa lung abscess. Case Presentation. An 86-year-old male was admitted to the hospital with fever, dry cough, and fatigue. PCR testing from a nasopharyngeal swab confirmed SARS-CoV-2 infection. An initial CT scan of the chest showed COVID-19 typical peripheral ground-glass opacities of both lungs. The patient required supplemental oxygen, and anti-inflammatory treatment with corticosteroids was initiated. After four weeks of corticosteroid therapy, the follow-up CT scan of the chest suddenly showed a new cavernous formation in the right lower lung lobe. The patient's condition deteriorated requiring high-flow oxygen support. Consequently, the patient was transferred to the intensive care unit. Empiric therapy with intravenous piperacillin/tazobactam was started. Mycobacterial and fungal infections were excluded, while all sputum samples revealed cultural growth of P. aeruginosa. Antimicrobial susceptibility testing showed resistance to meropenem, imipenem, ciprofloxacin, gentamicin, and tobramycin. After two weeks of treatment with intravenous piperacillin/tazobactam, the clinical condition improved significantly, and supplemental oxygen could be stopped. Subsequently antimicrobial treatment was switched to oral delafloxacin facilitating an outpatient management. CONCLUSION: Our case demonstrates that long-term corticosteroid administration in severe COVID-19 can result in severe bacterial coinfections including P. aeruginosa lung abscess. To our knowledge, this is the first reported case of a P. aeruginosa lung abscess whose successful therapy included oral delafloxacin. This is important because real-life data for the novel drug delafloxacin are scarce, and fluoroquinolones are the only reliable oral treatment option for P. aeruginosa infection. Even more importantly, our case suggests an oral therapy option for P. aeruginosa lung abscess in case of resistance to ciprofloxacin, the most widely used fluoroquinolone in P. aeruginosa infection.

qSOFA score poorly predicts critical progression in COVID-19 patients.

BACKGROUND: In December 2019, the new virus infection coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged. Simple clinical risk scores may improve the management of COVID-19 patients. Therefore, the aim of this pilot study was to evaluate the quick Sequential Organ Failure Assessment (qSOFA) score, which is well established for other diseases, as an early risk assessment tool predicting a severe course of COVID-19. METHODS: We retrospectively analyzed data from adult COVID-19 patients hospitalized between March and July 2020. A critical disease progress was defined as admission to intensive care unit (ICU) or death. RESULTS: Of 64 COVID-19 patients, 33% (21/64) had a critical disease progression from which 13 patients had to be transferred to ICU. The COVID-19-associated mortality rate was 20%, increasing to 39% after ICU admission. All patients without a critical progress had a qSOFA score ≤ 1 at admission. Patients with a critical progress had in only 14% (3/21) and in 20% (3/15) of cases a qSOFA score ≥ 2 at admission (p = 0.023) or when measured directly before critical progression, respectively, while 95% (20/21) of patients with critical progress had an impairment oxygen saturation (SO2) at admission time requiring oxygen supplementation. CONCLUSION: A low qSOFA score cannot be used to assume short-term stable or noncritical disease status in COVID-19.

Rare manifestation of a large stenosing gastrointestinal tumor caused by Mycobacterium tuberculosis in a previously healthy man from Austria.

BACKGROUND: Gastrointestinal tuberculosis (TB) is a rare manifestation in low TB-incidence countries such as Austria. It is usually seen in immunocompromised patients or in migrants being more susceptible for extrapulmonary disease manifestations. CASE DESCRIPTION: We report a very rare manifestation of severe gastrointestinal TB in a 49-year-old previously healthy man from Upper Austria. Endoscopy showed a large tumor mass obstructing about 2/3 of the lumen of the cecum. Positron emission tomography/computed tomography scan revealed not only a high metabolic activity in the tumor mass, but also active pulmonary lesions in both upper lung lobes. Bronchial secretion showed acid-fast bacilli in the microscopy and polymerase chain reaction was positive for M. tuberculosis complex. Phenotypic resistance testing showed no resistance for first-line anti-TB drugs. Treatment with isoniazid, rifampicin, pyrazinamide and ethambutol was initiated. Based on therapeutic drug monitoring, the standard treatment regime was adapted to rifampicin high dose. TB treatment was well tolerated and the patient achieved relapse-free cure one year after the end of treatment. CONCLUSION: Gastrointestinal involvement mimicking an intestinal tumor is a very rare TB manifestation in previously healthy Austrians. However, it should be kept in mind due to increasing migration from countries with higher rates of extrapulmonary TB and due to an increasing number of immunocompromised patients. TB telephone consultations can support medical professionals in the diagnosis and the management of complex TB patients. TB management is currently at a transitional stage from a programmatic to personalized management concept including therapeutic drug monitoring or biomarker-guided treatment duration to achieve relapse-free cure.

Seroprevalence of Aspergillus-Specific IgG Antibody among Mozambican Tuberculosis Patients.

BACKGROUND: Chronic pulmonary aspergillosis (CPA) is a life-threatening sequel in patients with pulmonary tuberculosis (PTB). Aspergillus-specific IgG antibody is a useful diagnostic biomarker supporting CPA diagnosis, especially in countries with limited health recourses. METHODS: We conducted a prospective pilot study to assess the seroprevalence of Aspergillus-specific IgG antibodies among 61 Mozambican tuberculosis patients before, during, and after the end of TB treatment. Aspergillus-specific IgG antibody levels were measured using the ImmunoCAP®. RESULTS: In this study, 3 out of 21 HIV-negative PTB patients had a positive Aspergillus-specific IgG antibody level before, during, and after the end of TB treatment. Antibody levels were 41.1, 45.5, and 174 mg/L at end of treatment (EOT), respectively. Additionally, two HIV-negative PTB patients with negative Aspergillus-specific IgG antibody levels at baseline became seropositive at EOT (41.9 and 158 mg/L, respectively). Interestingly, none of the HIV-positive PTB patients (40/61) had a positive Aspergillus-specific IgG antibody level at any time, neither at baseline nor at EOT. Probable CPA was diagnosed in one HIV-negative patient (5%; 1/20). CONCLUSION: Seroprevalence of Aspergillus-specific IgG antibody may differ between HIV-negative and HIV-positive Mozambican PTB patients. Future studies evaluating post-tuberculosis lung disease should integrate CPA as a life-threatening sequel to PTB.

Using Interleukin 6 and 8 in Blood and Bronchoalveolar Lavage Fluid to Predict Survival in Hematological Malignancy Patients With Suspected Pulmonary Mold Infection.

Background: Molds and other pathogens induce elevated levels of several cytokines, including interleukin (IL)-6 and IL-8. The objective of this study was to investigate the prognostic value of IL-6 and IL-8 as well as fungal biomarkers in blood and bronchoalveolar lavage fluid (BAL) for overall survival in patients with underlying hematological malignancies and suspected mold infection. Methods: This cohort study included 106 prospectively enrolled adult cases undergoing bronchoscopy. Blood samples were collected within 24 h of BAL sampling and, in a subset of 62 patients, serial blood samples were collected up until 4 days after bronchoscopy. IL-6, IL-8, and other cytokines as well as galactomannan (GM) and ß-D-glucan (BDG) were assayed in blood and BAL fluid and associations with overall mortality were assessed at the end of the study using receiver operating characteristic (ROC) curve analysis. Results: Both blood IL-8 (AUC 0.731) and blood IL-6 (AUC 0.699) as well as BAL IL-6 (AUC 0.763) and BAL IL-8 (AUC 0.700) levels at the time of bronchoscopy were predictors of 30-day all-cause mortality. Increasing blood IL-6 levels between bronchoscopy and day four after bronchoscopy were significantly associated with higher 90-day mortality, with similar findings for increasing IL-8 levels. In ROC analysis the difference of blood IL-8 levels between 4 days after bronchoscopy and the day of bronchoscopy had an AUC of 0.829 (95%CI 0.71-0.95; p < 0.001) for predicting 90-day mortality. Conclusions: Elevated levels of IL-6 and IL-8 in blood or BAL fluid at the time of bronchoscopy, and rising levels in blood 4 days following bronchoscopy were predictive of mortality in these patients with underlying hematological malignancy who underwent bronchoscopy for suspected mold infection.

Diagnosis of invasive aspergillosis in hematological malignancy patients: Performance of cytokines, Asp LFD, and Aspergillus PCR in same day blood and bronchoalveolar lavage samples.

BACKGROUND: Aspergillus spp. induce elevated levels of several cytokines. It remains unknown whether these cytokines hold value for clinical routine and enhance diagnostic performances of established and novel biomarkers/tests for invasive aspergillosis (IA). METHODS: This cohort study included 106 prospectively enrolled (2014-2017) adult cases with underlying hematological malignancies and suspected pulmonary infection undergoing bronchoscopy. Serum samples were collected within 24 hours of bronchoalveolar lavage fluid (BALF) sampling. Both, serum and BALF samples were used to evaluate diagnostic performances of the Aspergillus-specific lateral-flow device test (LFD), Aspergillus PCR, ß-D-glucan, and cytokines that have shown significant associations with IA before. RESULTS: Among 106 cases, 11 had probable IA, and 32 possible IA; 80% received mold-active antifungals at the time of sampling. Diagnostic tests and biomarkers showed better performance in BALF versus blood, with the exception of serum interleukin (IL)-8 which was the most reliable blood biomarker. Combinations of serum IL-8 with either BALF LFD (sensitivity 100%, specificity 94%) or BALF PCR (sensitivity 91%, specificity 97%) showed promise for differentiating probable IA from no IA. CONCLUSIONS: High serum IL-8 levels were highly specific, and when combined with either the BALF Aspergillus-specific LFD, or BALF Aspergillus PCR also highly sensitive for diagnosis of IA.

Evaluation of the new AspID polymerase chain reaction assay for detection of Aspergillus species: A pilot study.

The newly developed AspID PCR assay for detection of Aspergillus spp. was evaluated with an interlaboratory quality control programme panel and human bronchoalveolar lavage fluid (BALF) samples. With the quality control programme, 8 out of 9 panel members were correctly identified. With the clinical study, 36 BALF samples that had been obtained from 18 patients with invasive pulmonary aspergillosis (IPA) and 18 without IPA were investigated. Sensitivity, specificity, positive and negative likelihood ratio for the AspID assay were 94.1% (95% CI 73.3-99.9), 76.5% (95% CI 50.1-93.2), 4 (95% CI 1.7-9.5) and 0.1 (95% CI 0.01-0.5) respectively.

Clinical evaluation of the newly formatted lateral-flow device for invasive pulmonary aspergillosis.

The study evaluated the newly formatted Aspergillus-specific lateral-flow-device (LFD), and compared its performance to the original prototype "old" LFD test using BALF samples from 28 patients (14 patients with probable/proven invasive pulmonary aspergillosis [IPA] and 14 patients with no evidence for IPA). A total of 10/14 (71%) of BALF samples from patients with probable/proven IPA resulted positive with the new LFD, including 8/9 with true-positive and 2/5 with false-negative results with the old LFD. All 14 samples from patients without IPA resulted negative with the new LFD; specificity of the new LFD was significantly improved compared to the old LFD.

Levels of interleukin (IL)-6 and IL-8 are elevated in serum and bronchoalveolar lavage fluid of haematological patients with invasive pulmonary aspergillosis.

Aspergillus spp. have been shown to induce T-helper cell (Th) 1 and Th17 subsets resulting in elevated levels of several cytokines. The objective of this study was to analyse a bundle of cytokines in serum and bronchoalveolar lavage fluid (BALF) in patients with and without invasive pulmonary aspergillosis (IPA). This nested case-control analysis included 10 patients with probable/proven IPA and 20 matched controls without evidence of IPA, out of a pool of prospectively enrolled (2014-2017) adult cases with underlying haematological malignancies and suspected pulmonary infection. Serum samples were collected within 24 hours of BALF sampling. All samples were stored at -70°C for retrospective determination of cytokines. IL-6 and IL-8 were significantly associated with IPA in both serum (P = .011 and P = .028) and BALF (P = .006 and P = .012, respectively), and a trend was observed for serum IL-10 (P = .059). In multivariate conditional logistic regression analysis, IL-10 remained a significant predictor of IPA in serum and IL-8 among BALF cytokines. In conclusion, levels of IL-6 and IL-8 were significantly associated with probable/proven IPA, and a similar trend was observed for serum IL-10. Future cohort studies should determine the diagnostic potential of these cytokines for IPA, and evaluate combinations with other IPA biomarkers/diagnostic tests.

Lateral Flow Assays for the Diagnosis of Invasive Aspergillosis: Current Status.

PURPOSE OF REVIEW: Diagnosis during early stages of invasive aspergillosis (IA) and targeted antifungal treatment has the potential to improve survival significantly. Despite advances in the diagnostic arsenal, invasive mold infections remain difficult to diagnose-especially at early stages before typical radiological signs develop. Varying availability and time-to-results are important limitations of current approved biomarkers and molecular assays for diagnosis of IA. Here, we will give an update on the Aspergillus-specific lateral-flow device (LFD) test. We further review promising findings on feasibility of point-of-care (POC) detection of urinary excreted fungal galactomannan-like antigens. RECENT FINDINGS: POC LFD assays for detection of Aspergillus antigens are currently in development. The Aspergillus-specific LFD test, which is based on the JF5 antibody (Ab), detects an extracellular glycoprotein antigen secreted during active growth of Aspergillus spp. The test has shown promising results in various studies. In addition, a monoclonal Ab476-based LFD for POC detection of urinary excreted fungal galactomannan-like antigens has been developed but needs further validation. SUMMARY: Important advances have been made in the development of LFD assays for IA. Most promising is the Aspergillus-specific LFD test; commercial availability is still pending, however. The search for reliable POC tests for other molds, including mucorales, continues.

Galactomannan testing and Aspergillus PCR in same-day bronchoalveolar lavage and blood samples for diagnosis of invasive aspergillosis.

In recent years galactomannan antigen testing (GM) and also Aspergillus PCR have become increasingly important for diagnosis of invasive aspergillosis (IA). Whether or not these tests need to be performed with bronchoalveolar lavage fluid (BALF; i.e., primary site of infection), or testing of blood samples is sufficient, remains, however, a matter of debate. We evaluated the diagnostic performance of GM ELISA, and Aspergillus PCR by using BALF samples and blood samples obtained at the same day from a total of 53 immunocompromised patients (16 with probable/proven IA and 37 with no evidence of IA according to the revised EORTC/MSG criteria; 38 patients with hematological malignancies were prospectively enrolled at the Medical University of Graz, Austria, 15 patients with mixed underlying diseases at the Mannheim University Hospital). Patients with possible IA were excluded from this analysis. A total of 34/53 (64%) of all patients and 12/16 (75%) of patients with probable/proven IA received mold-active antifungal prophylaxis/therapy at the time of the BALF procedure. Sensitivities of GM and Aspergillus PCR were 38% and 44% in BALF, and 31% and 0% in blood, respectively. Best sensitivity (75%) for detecting proven/probable IA was achieved when BALF Aspergillus PCR, BALF GM (>1.0 ODI), BALF-culture and serum-GM (>0.5 ODI) were combined (specificity 95%). In conclusion, sensitivities of the evaluated diagnostic tests-when interpreted on their own-were low in BALF and even lower in blood, sensitivities increased markedly when diagnostic tests were combined.

Point of Care Testing for the Diagnosis of Fungal Infections: Are We There Yet?

Diagnostic tools for invasive fungal infections have continuously improved within the last decades. Nowadays, cultural methods, antigen testing, and molecular tests, such as polymerase chain reaction, are widely used. These methods, however, are accompanied with different limitations as various availability, various turnaround time or high costs. A new generation of point-of-care test has shown promising results in various studies and may overcome some of these limitations. We therefore reviewed the literature for the most promising new point-of-care tests for invasive aspergillosis (Aspergillus-specific lateral-flow device test, Aspergillus proximity ligation antigen assay), cryptococcosis (cryptococcal lateral-flow assay), and for histoplasmosis (loop-mediated isothermal amplification assay).