Reducing Microbial Contamination in Hematopoietic Stem Cell Products and Quality Improvement Strategy: Retrospective Analysis of 1996-2021 Data.

Background: Sterility and safety assurance of hematopoietic stem cell (HSC) products is critical in transplantation. Microbial contamination can lead to product disposal and increases the risk of unsuccessful clinical outcomes. Therefore, it is important to implement and maintain good practice guidelines and regulations for the HSC collection and processing unit in each hospital. We aimed to share our experiences and suggest strategies to improve the quality assurance of HSC processing. Methods: We retrospectively analyzed microbial culture results of 11,743 HSC products processed over a 25-year period (January 1996 to May 2021). Because of reorganization of the HSC management system in 2008, the 25-year period was divided into periods 1 (January 1996 to December 2007) and 2 (January 2008 to May 2021). We reviewed all culture results of the HSC products and stored aliquot samples and collected culture results for peripheral blood and catheter samples. Results: Of the 11,743 products in total, 35 (0.3%) were contaminated by microorganisms, including 19 (0.5%) of 3,861 products during period 1 and 16 (0.2%) of 7,882 products during period 2. Penicillium was the most commonly identified microorganism (15.8%) during period 1 and coagulase-negative Staphylococcus was the most commonly identified (31.3%) during period 2. HSC product contamination occurred most often during HSC collection and processing. Conclusions: The contamination rate decreased significantly during period 2, when the HSC management system was reorganized. Our results imply that handling HSC products by trained personnel and adopting established protocols, including quality assurance programs, aid in decreasing the contamination risk.

Predictive and prognostic factors associated with unliquefied pyogenic liver abscesses.

INTRODUCTION: Poor liquefaction of pyogenic liver abscesses, which makes drainage impossible at the time of diagnosis, is not infrequent. The impact of poor liquefaction and subsequent drainage failure on clinical outcomes is unknown. METHODS: We conducted a retrospective study with all patients diagnosed with liver abscesses from July 2017 through June 2020. Late drainage (LD) was defined as drainage performed ≥48 h after diagnosis due to poor liquefaction. Logistic regression was performed to identify the factors associated with late or non-drainage (LD/ND). The Cox proportional hazard model was used to identify the variables related to abscess recurrence by 90 days after diagnosis. RESULTS: A total of 153 patients were included. Thirty (19.6%) patients underwent LD and 54 (35.3%) did not undergo drainage. Other than non-cystic appearance, LD/ND was associated with smaller size (adjusted odds ratio [aOR] 0.85, 95% confidence interval [CI] 0.73-0.98, p = 0.031) and culture-negativity (aOR 2.69, 95% CI 1.14-6.67, p = 0.027). Current hepatopancreaticobiliary malignancy was the only significant predictor of 90-day recurrence. Neither LD/ND (OR, 0.56; 95% CI, 0.13-2.41; p = 0.426) nor LD (OR, 1.26; 95% CI, 0.23-5.55; p = 0.719) was associated with recurrence by 90 days. The incidence of late complications was reduced by drainage, without a reduction in the duration of hospitalization. CONCLUSION: Several clinical features were associated with undrainable liver abscesses. Neither LD/ND nor ND had an adverse impact on clinical outcomes.

Pharmacokinetic/pharmacodynamic parameters of vancomycin for predicting clinical outcome of enterococcal bacteremia.

PURPOSE: To find pharmacokinetic/pharmacodynamic parameters of vancomycin associated with the optimal outcome of severe infection due to Enterococcus species. METHODS: We retrospectively reviewed enterococcal bacteremia cases treated with vancomycin from January 2015 to December 2020. The primary outcome was 30-day mortality. We calculated cutoff values of the ratio of vancomycin area under the concentration-time curve over 24 h to the minimum inhibitory concentration (AUC24/MIC) and trough concentration (Ctrough) during the initial 72 h of treatment. The optimal cutoff value was determined using the Youden index. Binary variables created based on these cutoffs were further assessed using multivariable analysis. RESULTS: A total of 65 patients were included. The majority (87.7%) had solid or hematologic malignancies. Thirty-day mortality and nephrotoxicity occurred in nine (13.4%) and 14 (21.5%) patients, respectively. Both vancomycin AUC24/MIC and Ctrough showed fair performance in predicting 30-day mortality (AUC of receiver-operator curve for AUC24/MIC, 0.712; 95% confidence interval [CI] 0.539-0.886; AUC for Ctrough, 0.760; 95% CI 0.627-0.892; pairwise AUC comparison: p = 0.570). Ctrough ≥ 13.94 µg/mL, but not AUC24/MIC ≥ 504, had a significant association with 30-day mortality after adjusting for confounders (odds ratio, 8.40; 95% CI 1.60-86.62; p = 0.010). CONCLUSION: Mean Ctrough ≥ 13.94 µg/mL during the initial 72 h was associated with higher 30-day mortality in enterococcal bacteremia. Further studies are warranted to elucidate optimal pharmacokinetic targets for enterococcal bacteremia.

Fatal Prototheca zopfii Algaemia in a Patient with Acute Lymphoblastic Leukemia: a Case Report.

BACKGROUND: Prototheca algaemia is a rare but life-threatening disease that occurs primarily in immunocompromised patients. We report a fatal case of Prototheca zopfii bloodstream infection in a 54-year-old woman receiving chemotherapy for relapsed acute lymphoblastic leukemia. METHODS: The isolate was identified using an automated biochemical identification system (VITEK 2; bioMerieux) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (VITEK MS; bioMerieux). Partial 18S and 28S rDNA sequencing was performed for definitive identification and genotyping. RESULTS: The patient had persistent neutropenic fever, and isolates from blood culture were identified as P. zopfii. Sequencing was performed and the isolate was confirmed to be P. zopfii genotype 2, which was newly named as P. bovis. The patient was treated with liposomal amphotericin B but died of septic shock. CONCLUSIONS: Prototheca spp. should be considered an emerging pathogen, especially in immunocompromised patients, due to its ubiquitous nature.

The impact of vancomycin-resistant Enterococcus (VRE) screening policy change on the incidence of healthcare-associated VRE bacteremia.

OBJECTIVE: To evaluate the impact of a vancomycin-resistant Enterococcus (VRE) screening policy change on the incidence of healthcare-associated (HA)-VRE bacteremia in an endemic hospital setting. DESIGN: A quasi-experimental before-and-after study. SETTING: A 1,989-bed tertiary-care referral center in Seoul, Republic of Korea. METHODS: Since May 2010, our hospital has diminished VRE screening for admitted patients transferred from other healthcare facilities. We assessed the impact of this policy change on the incidence of HA-VRE bacteremia using segmented autoregression analysis of interrupted time series from January 2006 to December 2014 at the hospital and unit levels. In addition, we compared the molecular characteristics of VRE blood isolates collected before and after the screening policy change using multilocus sequence typing and pulsed-field gel electrophoresis. RESULTS: After the VRE screening policy change, the incidence of hospital-wide HA-VRE bacteremia increased, although no significant changes of level or slope were observed. In addition, a significant slope change in the incidence of HA-VRE bacteremia (change in slope, 0.007; 95% CI, 0.001-0.013; P = .02) was observed in the hemato-oncology department. Molecular analysis revealed that various VRE sequence types appeared after the policy change and that clonally related strains became more predominant (increasing from 26.1% to 59.3%). CONCLUSIONS: The incidence of HA-VRE bacteremia increased significantly after VRE screening policy change, and this increase was mainly driven by high-risk patient populations. When planning VRE control programs in hospitals, different approaches that consider risk for severe VRE infection in patients may be required.

Clinical Usefulness of Fungal Culture of EBUS-TBNA Needle Rinse Fluid and Core Tissue.

PURPOSE: The diagnosis of pulmonary fungal infections is challenging due to the difficulty of obtaining sufficient specimens. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) needle rinse fluid has become an emerging diagnostic material. This study evaluated the role of routine fungal culture from EBUS-TBNA needle rinse fluid, in addition to histopathologic examination and fungal culture of EBUS-TBNA core tissue, in the diagnosis of pulmonary fungal infections. MATERIALS AND METHODS: Among patients who underwent EBUS-TBNA, those with results for at least one of three tests (histopathologic examination, fungal culture of EBUS-TBNA core tissue or needle rinse fluid) were included. Patients with a positive test were divided into two groups (clinical fungal infection and suspected fungal contamination) according to their clinical assessment and therapeutic response to antifungal. RESULTS: Of 6072 patients, 41 (0.7%) had positive fungal tests and 9 (22%) were diagnosed as clinical fungal infection. Of the 5222 patients who were evaluated using a fungal culture from EBUS-TBNA needle rinse fluid, 35 (0.7%) had positive results. However, only 4 out of 35 (11.4%) were classified as clinical fungal infection. Positive results were determined in 4 of the 68 (5.9%) evaluated by a fungal culture of EBUS-TBNA core tissue, and all were diagnosed as clinical fungal infection. CONCLUSION: Routine fungal culture of EBUS-TBNA needle rinse fluid is not useful due to the low incidence of fungal infection and high rate of contamination. However, fungal culture of EBUS-TBNA core tissue and needle rinse fluid should be considered in patients with clinically suspected fungal infection.

Cefepime Versus Cefepime Plus Amikacin as an Initial Antibiotic Choice for Pediatric Cancer Patients With Febrile Neutropenia in an Era of Increasing Cefepime Resistance.

BACKGROUND: We investigated the treatment outcomes before and after the addition of amikacin to cefepime monotherapy as an initial empirical antibiotic treatment in pediatric cancer patients with febrile neutropenia. METHODS: This was a retrospective historical cohort study. The subjects were pediatric cancer patients who visited the emergency room at the Samsung Medical Center, Seoul, Korea, due to chemotherapy-induced febrile neutropenia, between January 2011 and December 2016. Since September 2014, the empirical antimicrobial treatment regimen for febrile neutropenia was changed from high-dose cefepime monotherapy to combination therapy of adding a single dose of amikacin. RESULTS: Two hundred twenty-five bacteremia episodes in 164 patients were reported during the study period. Bacteremia caused by cefepime-resistant Gram-negative bacteria was observed in 16% of patients before September 2014 and in 21% of the patients after September 2014 (P = 0.331). Use of appropriate empirical antibiotic treatments increased from 62% to 83% following addition of amikacin to cefepime treatment (P = 0.003). The duration of fever was shorter in the cefepime plus amikacin group than in the cefepime group (22 vs. 34 hours, P = 0.014); however, rates of septic shock and pediatric intensive care unit hospitalizations were not significantly different between the 2 groups (septic shock, both 7%, P = 0.436; pediatric intensive care unit 3% vs. 1%, P = 0.647). CONCLUSIONS: We observed no additional benefit of amikacin addition to high-dose cefepime monotherapy. Therefore, adding amikacin to cefepime monotherapy in conditions where cefepime-resistant Gram-negative bacteremia amounts to 20% or less may not be justified.

Characteristics and Clinical Outcomes of Extended-Spectrum beta-lactamase-producing Klebsiella pneumoniae Bacteremia in Cancer Patients.

BACKGROUND: Cancer patients can be at a higher risk of infection due to drug-resistant bacteria than the general population for various reasons. We performed a retrospective study to evaluate possible risk factors and outcomes of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-KP) bacteremia in cancer patients. MATERIALS AND METHODS: Cases were divided into two groups based on whether or not the isolated strain produced ESBL and multivariable regressions were done to identify possible risk factors of ESBL-KP bacteremia and mortality. For ESBL-producing strain, additional molecular analysis was done. RESULTS: 278 cases with KP bacteremia were identified between 2010 and 2012, of which ESBL-producers were 50 (18%). The presence of percutaneous drainage catheter [odds ratio (OR) 4.99, P <0.001] and prior exposure to certain classes of antibiotics including third-generation cephalosporin (OR 2.14, P = 0.03) had significant associations with ESBL-KP bacteremia. Individuals who died within 14 days after the onset of KP bacteremia were more likely to have higher mean Pitt bacteremia score (1.56 in survival group vs. 3.43 in mortality group, P <0.001), hemodialysis (OR 17.03, P = 0.01) and chronic liver disease (OR 5.57, P = 0.01). Although 14-day mortality was higher with ESBL production (OR 2.76, P = 0.04), no significant differences in 30-day mortality (OR 1.67, P = 0.20) and other morbidity indices were observed. 49 ESBL-KP isolates, 65.4% of them produced CTX-M-14 and CTX-M-15 enzymes, and ST711 was the most common. CONCLUSION: There were several differences in clinical characteristics between ESBL-KP and non-ESBL-KP bacteremia in cancer patients, similar to previous reports including non-cancer patients.

A nonsense variant in NME5 causes human primary ciliary dyskinesia with radial spoke defects.

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder characterized by defects in the function or structure of motitle cilia. In most cases, causative variants result in axonemal dynein arm anomalies, however, PCD due to radial spoke (RS) and central pair (CP) of microtubules has been rarely reported. To identify the molecular basis of PCD characterized by RS/CP defects, we performed whole exome sequencing in PCD patients with RS/CP defects. We identified a homozygous nonsense variant (c.572G>A; p.Trp191*) in NME5, which encodes a protein component of the RS neck, in one PCD patient with situs solitus. Morpholino knockdown of nme5 in zebrafish embryos resulted in motile cilia defects with phenotypes compatible with ciliopathy. This is the first study to show NME5 as a PCD-causative gene in humans. Our findings indicate that NME5 screening should be considered for PCD patients with RS/CP defects.

Prognostic factors associated with long-term mortality in 1445 patients with nontuberculous mycobacterial pulmonary disease: a 15-year follow-up study.

Limited data are available regarding the prognostic factors for patients with nontuberculous mycobacterial pulmonary disease (NTM-PD). We investigated the prognostic factors associated with long-term mortality in NTM-PD patients after adjusting for individual confounders, including aetiological organism and radiological form.A total of 1445 patients with treatment-naïve NTM-PD who were newly diagnosed between July 1997 and December 2013 were included. The aetiological organisms were as follows: Mycobacterium avium (n=655), M. intracellulare (n=487), M. abscessus (n=129) and M. massiliense (n=174). The factors associated with mortality in NTM-PD patients were analysed using a multivariable Cox model after adjusting for demographic, radiological and aetiological data.The overall 5-, 10- and 15-year cumulative mortality rates for the NTM-PD patients were 12.4%, 24.0% and 36.4%, respectively. On multivariable analysis, the following factors were significantly associated with mortality in NTM-PD patients: old age, male sex, low body mass index, chronic pulmonary aspergillosis, pulmonary or extrapulmonary malignancy, chronic heart or liver disease and erythrocyte sedimentation rate. The aetiological organism was also significantly associated with mortality: M. intracellulare had an adjusted hazard ratio (aHR) of 1.40, 95% CI 1.03-1.91; M. abscessus had an aHR of 2.19, 95% CI 1.36-3.51; and M. massiliense had an aHR of 0.99, 95% CI 0.61-1.64, compared to M. avium Mortality was also significantly associated with the radiological form of NTM-PD for the cavitary nodular bronchiectatic form (aHR 1.70, 95% CI 1.12-2.59) and the fibrocavitary form (aHR 2.12, 95% CI 1.57-3.08), compared to the non-cavitary nodular bronchiectatic form.Long-term mortality in patients with NTM-PD was significantly associated with the aetiological NTM organism, cavitary disease and certain demographic characteristics.

Clinical Characteristics and Outcomes of Surgically Resected Solitary Pulmonary Nodules Due to Nontuberculous Mycobacterial Infections.

BACKGROUND: Limited data are available regarding the detailed characteristics and outcomes of surgically resected nontuberculous mycobacterial (NTM) granulomas. METHODS: We evaluated the characteristics of 49 NTM granulomas presenting as solitary pulmonary nodules (SPNs) between January 2007 and December 2016. RESULTS: Twenty-five patients (51%) were male and 27 (55%) were never-smokers. Seven (14%) patients had a history of tuberculosis. More than half (51%) of patients were asymptomatic. On chest computed tomography, the median SPN diameter was 18 mm, and approximately half of all SPNs (49%) were located in the upper lobes on chest computed tomography. NTM strain were preoperatively isolated from sputum (46%, 12/26), bronchial wash fluid (54%, 14/26), and needle biopsy specimens (12%, 3/26). Mycobacterium avium (71%, 22/31) was the organism most commonly isolated, followed by Mycobacterium intracellulare (16%, 5/31). Postoperative pneumothorax and atelectasis developed in four (8%) patients and one (2%) patient, respectively. Five patients received postoperative antibiotic therapy. Over a median follow-up period of 18.0 months, one patient with residual lesions after surgery started macrolide-based therapy due to aggravated symptoms. CONCLUSIONS: Most NTM granulomas can be treated completely by surgical resection without antibiotic therapy, and microbiological examination of surgical specimens is important for optimal management.

Clinical Significance of Isolates Known to Be Blood Culture Contaminants in Pediatric Patients.

Background and objectives: The objective of this study was to investigate the clinical significance of isolates from blood stream infection known to be blood culture contaminants in pediatric patients. Materials and Methods: Microbiological reports and medical records of all blood culture tests issued from 2002 to 2012 (n = 76,331) were retrospectively reviewed. Evaluation for potential contaminants were done by reviewing medical records of patients with the following isolates: coagulase-negative Staphylococcus, viridans group Streptococcus, Bacillus, Corynebacterium, Micrococcus, Aerococcus, and Proprionibacterium species. Repeated cultures with same isolates were considered as a single case. Cases were evaluated for their status as a pathogen. Results: Coagulase-negative Staphylococcus had clinical significance in 23.8% of all cases. Its rate of being a true pathogen was particularly high in patients with malignancy (43.7%). Viridans group Streptococcus showed clinical significance in 46.2% of all cases. Its rate of being a true pathogen was similar regardless of the underlying morbidity of the patient. The rate of being a true pathogens for remaining isolates was 27.7% for Bacillus and 19.0% for Corynebacterium species. Conclusions: Coagulase-negative Staphylococcus and viridans group Streptococcus isolates showed high probability of being true pathogens in the pediatric population, especially in patients with underlying malignancy.

Treatment of community-onset pneumonia in neutropenic cancer patients: ß-lactam monotherapy versus combination antibiotic regimens.

BACKGROUND: Although ß-lactam monotherapy may be sufficient in non-critically ill patients with community-acquired pneumonia, the value of combination antibiotic regimens in community-onset neutropenic pneumonia remains unclear. METHODS: A retrospective cohort study was conducted to compare the effects of combination antibiotic regimens to those of ß-lactam monotherapy in cancer patients with community-onset neutropenic pneumonia. Electronic medical records of patients diagnosed with community-onset neutropenic pneumonia between March 1995 and February 2015 at a tertiary care center were reviewed. RESULTS: During the study period, 165 cancer patients with community-onset neutropenic pneumonia were identified. Seventy-two patients received ß-lactam monotherapy and 93 received combination therapy (ß-lactam plus either a macrolide or fluoroquinolone). Causative pathogens were identified in 27.9% of the patients, and only two were positive for atypical pathogens. Although 30-day mortality was higher in the ß-lactam group (15.3% versus 4.3%; P = 0.015), combination therapy was not associated with a statistically significant survival benefit in the multivariate analysis (hazard ratio 0.85, 95% confidence interval 0.20-3.67; P = 0.827). Duration of neutropenia, C-reactive protein level, and Multinational Association for Supportive Care in Cancer risk index were significant factors for 30-day mortality. In a subgroup analysis of patients treated with cefepime, the most frequently used ß-lactam (63.0%), combination therapy also showed no significant survival benefit. CONCLUSIONS: Combination antibiotic regimens were not associated with a survival benefit over ß-lactam monotherapy in the treatment of community-onset neutropenic pneumonia. Unnecessary combination therapy should be reconsidered in cancer patients who are at high risk for adverse drug reactions and colonization with multi-drug resistant organisms.

Long-term natural history of non-cavitary nodular bronchiectatic nontuberculous mycobacterial pulmonary disease.

BACKGROUND: Information about the natural history of nontuberculous mycobacterial pulmonary disease (NTM-PD) is limited. The purpose of this study was to evaluate the long-term natural history of non-cavitary nodular bronchiectatic NTM-PD and the factors associated with treatment initiation and the frequency of spontaneous sputum culture conversion after diagnosis of NTM-PD. METHODS: We evaluated 1,021 patients with newly diagnosed non-cavitary nodular bronchiectatic NTM-PD caused by Mycobacterium avium complex or M. abscessus between 2003 and 2013. RESULTS: Of 1,021 patients, 562 (55%) initiated antibiotic treatment and 459 (45%) did not. Young age (adjusted hazard ratio [aHR] = 0.99; 95% confidence interval [CI] = 0.98-0.99), low body mass index (aHR = 0.96; 95% CI = 0.93-0.99), previous history of tuberculosis (aHR = 1.23; 95% CI = 1.01-1.50), respiratory complaints such as cough (aHR = 1.36; 95% CI = 1.05-1.75) and sputum production (aHR = 1.47; 95% CI = 1.13-1.91), and high number of involved lobes on high-resolution computed tomography (aHR = 1.22; 95% CI = 1.14-1.31) were associated with treatment initiation. Of 459 patients who did not initiate treatment, 157 (34%) showed spontaneous sputum culture conversion. None of the clinical factors was associated with spontaneous conversion. After spontaneous culture conversion, 26 of 157 (17%) showed redeveloped NTM-PD caused by a species different from the original species. CONCLUSIONS: The natural history of non-cavitary nodular bronchiectatic NTM-PD is variable. After diagnosis, the decision to initiate antibiotic therapy should be individualized based on consideration of the risk factors for disease progression. However, for patients who do not start antibiotic therapy, continuous and lifetime follow-up is recommended to manage underlying bronchiectasis and the possibility of late progression of NTM-PD.

Evaluation of a Carbapenem-Saving Strategy Using Empirical Combination Regimen of Piperacillin-Tazobactam and Amikacin in Hemato-Oncology Patients.

We implemented a carbapenem-saving strategy in hemato-oncology patients from 2013, using an empirical combination of piperacillin-tazobactam and amikacin for high-risk hemato-oncology patients with febrile neutropenia, who remain hemodynamically unstable > 72 hours despite initial cefepime treatment. All-cause mortality was not different between the two periods (6.54 and 6.57 deaths per 1,000 person-day, P = 0.926). Group 2 carbapenem use significantly decreased after strategy implementation (78.43 vs. 67.43 monthly days of therapy, P = 0.018), while carbapenem-resistant gram-negative bacilli did not show meaningful changes during the study period. Our carbapenem-saving strategy could effectively suppress carbapenem use without an increase of overall mortality.

Prospective monitoring of adenovirus infection and type analysis after allogeneic hematopoietic cell transplantation: A single-center study in Korea.

BACKGROUND: Epidemiologic studies of human adenovirus (HAdV) in allogeneic hematopoietic cell transplantation (HCT) recipients have been conducted mostly in European countries where HAdV 2 (species C) has been most prevalent in the community. The main objective of this study was to investigate the epidemiology and the characteristics of HAdV infection in Korean allogeneic HCT recipients (<19 years). METHODS: In a prospective study from April 2012 to September 2015, HAdV in blood, urine, and stool specimens were monitored weekly from transplantation to day 100 or after if clinically suspected. HAdV infection was defined as positive HAdV PCR result in any specimens regardless of symptoms. RESULTS: A total of 1734 specimens were collected from 57 consecutively enrolled recipients. The cumulative incidence of HAdV infection at day 100, and 1 year was 10%, and 20%, and the incidence of viremia was 2% and 6%, respectively. The median onset time from HCT to viremia was 221 days (range, 7-596 days). All viremia cases were caused by only HAdV 3 (species B), whereas several types were detected in stool. Among patients with HAdV infection, lower absolute lymphocyte counts and extensive chronic graft-vs-host disease were associated with viremia (P = .028 and P = .006, respectively). CONCLUSIONS: Compared to western studies, this study demonstrated a lower incidence and delayed onset of HAdV infections and HAdV 3 was most prevalent in Korea.

Treatment outcomes of macrolide-susceptible Mycobacterium abscessus lung disease.

Mycobacterium abscessus lung disease is difficult to treat due to inducible resistance to macrolides. However, 15%-20% of isolates are macrolide susceptible. In 14 patients with macrolide-susceptible M. abscessus lung disease, all isolates had nonfunctional erm(41) gene, and sputum culture conversion rate was achieved in 93% (13/14) following antibiotic therapy.