Omicron BA.2 breakthrough infection elicits CD8+ T cell responses recognizing the spike of later Omicron subvariants.

Here, we examine peripheral blood memory T cell responses against the SARS-CoV-2 BA.4/BA.5 variant spike among vaccinated individuals with or without Omicron breakthrough infections. We provide evidence supporting a lack of original antigenic sin in CD8+ T cell responses targeting the spike. We show that BNT162b2-induced memory T cells respond to the BA.4/BA.5 spike. Among individuals with BA.1/BA.2 breakthrough infections, IFN-γ-producing CD8+ T cell responses against the BA.4/BA.5 spike increased. In a subgroup with BA.2 breakthrough infections, IFN-γ-producing CD8+ T cell responses against the BA.2-mutated spike region increased and correlated directly with responses against the BA.4/BA.5 spike, indicating that BA.2 spike-specific CD8+ T cells elicited by BA.2 breakthrough infection cross-react with the BA.4/BA.5 spike. We identified CD8+ T cell epitope peptides that are present in the spike of BA.2 and BA.4/BA.5 but not the original spike. These peptides are fully conserved in the spike of now-dominant XBB lineages. Our study shows that breakthrough infection by early Omicron subvariants elicits CD8+ T cell responses that recognize epitopes within the spike of newly emerging subvariants.

Risk factors and clinical outcomes of cytomegalovirus diseases in hematologic malignancy patients without hematopoietic stem-cell transplantation.

PURPOSE: This study aims to evaluate the risk factors and prognosis for CMV diseases in hematologic malignancy patients without hematopoietic stem-cell transplantation (HSCT). METHODS: We performed a case-control study (1:2) between 2012 and 2022. Adults with pathologic-confirmed CMV diseases (n=60) among hematologic malignancy patients were matched and compared to whom without CMV disease. RESULTS: Lymphoma was the most common underlying malignancy, and gastrointestinal tract involvement was the most common CMV disease. In the case group, high-dose steroid administration and transfusion within one month before diagnosis were higher (p<0.001). Steroid administration (aOR=5.78; 95% confidence interval: 1.25-26.68, p=0.024), red blood cell transfusion within one month (aOR=14.63; 2.75-77.76, p=0.002), low BMI (aOR=13.46, 2.07-87.45, p=0.006), and hypoalbuminemia (aOR=26.48, 5.93-118.17, p<0.001) were independent risk factors associated with CMV disease. The 30-day mortality was higher in the case group and CMV disease was significantly associated with all-cause mortality (aOR=14.41, 3.23-64.31, p<0.001). CONCLUSION: In hematologic malignancy patients without HSCT, risk factors for CMV organ disease included high-dose steroid administration and RBC transfusion within one month, low BMI, and hypoalbuminemia. Overall mortality was significantly higher with CMV disease, and CMV disease occurrence was a significant risk factor for mortality.

Breakthrough invasive fungal infection in patients with myeloid malignancy receiving posaconazole tablet prophylaxis: Clinical features, risk factors, and posaconazole profiles.

Posaconazole (PSC) delayed-release tablet prophylaxis is the standard of care for preventing invasive fungal infection (IFI) in patients with acute myeloid leukemia undergoing myelosuppressive chemotherapy. The clinical features, risk factors, and PSC profiles of breakthrough IFI (bIFI) in patients receiving PSC tablet prophylaxis were investigated. A single-center retrospective cohort study was conducted, including adult patients with myeloid malignancy who received prophylactic PSC tablets while undergoing chemotherapy from June 2016 to June 2021. Logistic regression analysis was used to identify risk factors for bIFI. A receiver operating characteristic curve was used to predict the relationship between PSC trough level at steady state and bIFI. A total of 434 patients with myeloid malignancy who received PSC tablets were screened. A total of 10 patients with bIFI were compared with 208 non-IFI patients. There were four proven and six probable IFI cases, nine due to Aspergillus, and one due to Fusarium species. The bIFI patients had higher in-hospital mortality (30.0%) than the non-IFI patients (1.9%; P < 0.001). History of allogeneic hematopoietic stem cell transplantation (odds ratio [OR] 6.27; 95% confidence interval [CI] 1.63-24.09), prolonged neutropenia ≥28 days (OR 4.33; 95% CI 1.20-15.70), and low plasma PSC concentration <0.7 µg/ml (OR 16.33; 95% CI 4.15-64.26) were risk factors for bIFI. The optimal cutoff value of plasma PSC concentration predicting bIFI was 0.765 µg/ml (sensitivity, 60.0%; specificity, 91.3%; area under the curve, 0.746). bIFI was not uncommon in patients with myeloid malignancy receiving PSC tablet prophylaxis and associated with poor outcomes. Therapeutic drug monitoring may still be necessary, even in patients receiving PSC tablets.

Invasive fungal infections increase mortality in acute myeloid leukemia patients. This study investigated breakthrough invasive fungal infection cases in patients receiving posaconazole tablet prophylaxis. Our results will contribute to improving the outcome of patients with myeloid malignancy.

Corticosteroids reduce pathologic interferon responses by downregulating STAT1 in patients with high-risk COVID-19.

We do not yet understand exactly how corticosteroids attenuate hyperinflammatory responses and alleviate high-risk coronavirus disease 2019 (COVID-19). We aimed to reveal the molecular mechanisms of hyperinflammation in COVID-19 and the anti-inflammatory effects of corticosteroids in patients with high-risk COVID-19. We performed single-cell RNA sequencing of peripheral blood mononuclear cells (PBMCs) from three independent COVID-19 cohorts: cohort 1 was used for comparative analysis of high-risk and low-risk COVID-19 (47 PBMC samples from 28 patients), cohort 2 for longitudinal analysis during COVID-19 (57 PBMC samples from 15 patients), and cohort 3 for investigating the effects of corticosteroid treatment in patients with high-risk COVID-19 (55 PBMC samples from 13 patients). PBMC samples from healthy donors (12 PBMC samples from 12 donors) were also included. Cohort 1 revealed a significant increase in the proportion of monocytes expressing the long noncoding RNAs NEAT1 and MALAT1 in high-risk patients. Cohort 2 showed that genes encoding inflammatory chemokines and their receptors were upregulated during aggravation, whereas genes related to angiogenesis were upregulated during improvement. Cohort 3 demonstrated downregulation of interferon-stimulated genes (ISGs), including STAT1, in monocytes after corticosteroid treatment. In particular, unphosphorylated STAT-dependent ISGs enriched in monocytes from lupus patients were selectively downregulated by corticosteroid treatment in patients with high-risk COVID-19. Corticosteroid treatment suppresses pathologic interferon responses in monocytes by downregulating STAT1 in patients with high-risk COVID-19. Our study provides insights into the mechanisms underlying COVID-19 aggravation and improvement and the effects of corticosteroid treatment.

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.

Impact of vancomycin use trend change due to the availability of alternative antibiotics on the prevalence of Staphylococcus aureus with reduced vancomycin susceptibility: a 14-year retrospective study.

BACKGROUND: We investigated the trend change in vancomycin-intermediate Staphylococcus aureus (VISA)/heterogeneous VISA (hVISA) prevalence among methicillin-resistant S. aureus (MRSA) bacteremia strains and antistaphylococcal antibiotic use together with mutation studies of vancomycin resistance-related gene loci to evaluate the impact of changes in antibiotic use after new antistaphylococcal antibiotics became available. METHODS: Among 850 healthcare-associated MRSA isolates from 2006 to 2019 at a tertiary hospital in South Korea, hVISA/VISA was determined by modified PAP/AUC analysis, and the identified hVISA/VISA strains were genotyped. Gene mutations at vraSR, graSR, walKR, and rpoB were studied by full-length sequencing. Antistaphylococcal antibiotic use in 2005-2018 was analyzed. RESULTS: Two VISA and 23 hVISA strains were identified. The prevalence rate ratio of hVISA/VISA carrying mutations at the two-component regulatory systems among MRSA was 0.668 (95% CI 0.531-0.841; P = 0.001), and the prevalence rate ratio of hVISA/VISA carrying rpoB gene mutations was 1.293 (95% CI 0.981-1.702; 174 P = 0.068). Annual vancomycin use density analyzed by days of therapy (DOT) per 1,000 patient-days did not decrease significantly, however the annual average length of time analyzed by the number of days vancomycin was administered for each case showed a significantly decreasing trend. CONCLUSIONS: During the 14-year period when the average length of vancomycin therapy decreased every year with the availability of alternative antibiotics, the prevalence of hVISA/VISA did not decrease significantly. This seems to be because the resistant strains carrying the rpoB mutations increased despite the decrease in the strains carrying the mutations at the two-component regulatory systems.

A COVID-19 Exposure at a Dental Clinic Where Healthcare Workers Routinely Use Particulate Filtering Respirators.

Asymptomatic/mildly symptomatic coronavirus disease 2019 (COVID-19) patients produce a considerable amount of virus and transmit severe acute respiratory syndrome virus 2 (SARS-CoV-2) through close contact. Preventing in-hospital transmission of SARS-CoV-2 is challenging, since symptom-based screening protocols may miss asymptomatic/mildly symptomatic patients. In particular, dental healthcare workers (HCWs) are at high risk of exposure, as face-to-face contact and exposure to oral secretions is unavoidable. We report exposure of HCWs during dental procedures on a mild symptomatic COVID-19 patient. A 32-year-old male visited a dental clinic at a tertiary care hospital. He experienced mild cough, which started three days before the dental visit, but did not report his symptom during the entrance screening. He underwent several dental procedures and imaging for orthognathic surgery without wearing a mask. Seven HCWs were closely exposed to the patient during dental procedures that could have generated droplets and aerosols. One HCW had close contact with the patient during radiologic exams, and seven HCWs had casual contact. All HCWs wore particulate filtering respirators with 94% filter capacity and gloves, but none wore eye protection or gowns. The next day, the patient experienced dysgeusia and was diagnosed with COVID-19 with high viral load. All HCWs who had close contact with the patient were quarantined for 14 days, and polymerase chain reaction and antibody tests for SARS-CoV-2 were negative. This exposure event suggests the protective effect of particulate filtering respirators in dental clinics. The recommendations of different levels of personal protective equipment (PPE) for dental HCWs according to the procedure types should be established according to the planned procedure, the risk of COVID-19 infection of the patient, and the outbreak situation of the community.

Clinical and Virologic Effectiveness of Remdesivir Treatment for Severe Coronavirus Disease 2019 (COVID-19) in Korea: a Nationwide Multicenter Retrospective Cohort Study.

BACKGROUND: Remdesivir is widely used for the treatment of coronavirus disease 2019 (COVID-19), but controversies regarding its efficacy still remain. METHODS: A retrospective cohort study was conducted to evaluate the effect of remdesivir on clinical and virologic outcomes of severe COVID-19 patients from June to July 2020. Primary clinical endpoints included clinical recovery, additional mechanical ventilator (MV) support, and duration of oxygen or MV support. Viral load reduction by hospital day (HD) 15 was evaluated by calculating changes in cycle threshold (Ct) values. RESULTS: A total of 86 severe COVID-19 patients were evaluated including 48 remdesivir-treated patients. Baseline characteristics were not significantly different between the two groups. Remdesivir was administered an average of 7.42 days from symptom onset. The proportions of clinical recovery of the remdesivir and supportive care group at HD 14 (56.3% and 39.5%) and HD 28 (87.5% and 78.9%) were not statistically different. The proportion of patients requiring MV support by HD 28 was significantly lower in the remdesivir group than in the supportive care group (22.9% vs. 44.7%, P = 0.032), and MV duration was significantly shorter in the remdesivir group (average, 1.97 vs. 5.37 days; P = 0.017). Analysis of upper respiratory tract specimens demonstrated that increases of Ct value from HD 1-5 to 11-15 were significantly greater in the remdesivir group than the supportive care group (average, 10.19 vs. 5.36; P = 0.007), and the slope of the Ct value increase was also significantly steeper in the remdesivir group (average, 5.10 vs. 2.68; P = 0.007). CONCLUSION: The remdesivir group showed clinical and virologic benefit in terms of MV requirement and viral load reduction, supporting remdesivir treatment for severe COVID-19.

Ongoing outbreak of human adenovirus-associated acute respiratory illness in the Republic of Korea military, 2013 to 2018.

BACKGROUND/AIMS: Human adenovirus type 55 (HAdV-55), an emerging epidemic strain, has caused several large outbreaks in the Korean military since 2014, and HAdV-associated acute respiratory illness (HAdV-ARI) has been continuously reported thereafter. METHODS: To evaluate the epidemiologic characteristics of HAdV-ARI in the Korean military, we analyzed respiratory virus polymerase chain reaction (RV-PCR) results, pneumonia surveillance results, and severe HAdV cases from all 14 Korean military hospitals from January 2013 to May 2018 and compared these data with nationwide RV surveillance data for the civilian population. RESULTS: A total of 14,630 RV-PCRs was performed at military hospitals. HAdV (45.4%) was the most frequently detected RV, followed by human rhinovirus (12.3%) and influenza virus (6.3%). The percentage of the military positive for HAdV was significantly greater than the percentage of civilians positive for HAdV throughout the study period, with a large outbreak occurring during the winter to spring of 2014 to 2015. The outbreak continued until the end of the study, and non-seasonal detections increased over time. The reported number of pneumonia patients also increased during the outbreak. Case fatality rate was 0.075% overall but 15.6% in patients with respiratory failure. The proportion of severe patients did not change significantly during the study period. CONCLUSION: A large HAdV outbreak is currently ongoing in the Korean military, with a trend away from seasonality, and HAdV-55 is likely the predominant strain. Persistent efforts to control the outbreak, HAdV type-specific surveillance, and vaccine development are required.

Comparison of clinical characteristics and inflammatory cytokines between hypoxemic and non-hypoxemic human adenovirus 55 pneumonia.

BACKGROUND: Human adenovirus (HAdV) can cause severe community-acquired pneumonia, but there are few studies on the associated cytokine patterns. The purpose of this study was to analyze the relationship between inflammatory cytokine and severity of adenovirus pneumonia. METHODS: This was a prospective observational study. We evaluated pneumonia patients admitted to the Armed Forces Capital Hospital in Korea. On admission, blood samples were acquired from patients who showed signs of pneumonia. HAdV infection was diagnosed using Real-Q RV detection Kit, and types of HAdV were confirmed by nucleotide blast analysis. We used enzyme-linked immunosorbent assays (ELISAs) to quantify the serum levels of cytokines [interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, γ-interferon (IFN-γ), and IL-10]. We evaluated clinical characteristics and cytokine patterns. RESULTS: Of 74 pneumonia patients, respiratory specimens from 43 tested positive for HAdV-55, and the other 31 tested negatives. The length of hospital stay was significantly longer in the HAdV group. The serum concentrations of IL-6, IL-8, IL-10, and IFN-γ were all significantly higher in the HAdV group. Of the 43 HAdV pneumonia patients, 6 evidenced PaO2/FiO2 (PF) ratio <300, and 37 did not. Compared to the non-hypoxemic group, the hypoxemic group showed significantly lower lymphocyte and monocyte counts, and increased IL-6 and IFN-γ concentrations. Logistic regression analysis showed that the IL-6, IL-10, and IFN-γ were significantly associated with hypoxemia in the HAdV group. The IL-6, and IFN-γ levels correlated significantly with the PF ratio. CONCLUSIONS: We found that the levels IL-6, IL-10, and IFN-γ were significantly associated with hypoxemia in patients with HAdV-55 pneumonia.

Seroprevalence of neutralizing antibodies against human adenovirus type 55 in the South Korean military, 2018-2019.

We conducted a seroprevalence study of a large ongoing outbreak of human adenovirus type 55 (HAdV-55) among the military in South Korea. Serum samples were collected between 2018 and 2019 from military-exposed (military group) and non-exposed (non-military group) populations. The plaque reduction neutralization test (PRNT) was used to assess neutralization activity against HAdV-55. A total of 100 sera was collected from the non-military group, of which 18.8% showed HAdV-55 neutralizing antibody activity. Ninety-six sera were tested from the military group, which had significantly higher prevalence of neutralizing antibodies (56.0%, P <0.001). A significantly higher proportion of the military group had PRNT titers ≥1:1,000 than the non-military group (85.7% vs. 50.0%, P = 0.004). Among the military group, 48.9% of active-duty soldiers had PRNT titers ≥1:5,000, while none of the discharged civilians did (P = 0.007). In conclusion, Koreans were exposed to HAdV-55 in their communities, but the exposure risk was higher among people in military service.

Safe surgical tracheostomy during the COVID-19 pandemic: A protocol based on experiences with Middle East Respiratory Syndrome and COVID-19 outbreaks in South Korea.

BACKGROUND: A subset of patients with COVID-19 require intensive respiratory care and tracheostomy. Several guidelines on tracheostomy procedures and care of tracheostomized patients have been introduced. In addition to these guidelines, further details of the procedure and perioperative care would be helpful. The purpose of this study is to describe our experience and tracheostomy protocol for patients with MERS or COVID-19. MATERIALS AND METHODS: Thirteen patients with MERS were admitted to the ICU, 9 (69.2%) of whom underwent surgical tracheostomy. During the COVID-19 outbreak, surgical tracheostomy was performed in one of seven patients with COVID-19. We reviewed related documents and collected information through interviews with healthcare workers who had participated in designing a tracheostomy protocol. RESULTS: Compared with previous guidelines, our protocol consisted of enhanced PPE, simplified procedures (no limitation in the use of electrocautery and wound suction, no stay suture, and delayed cannula change) and a validated screening strategy for healthcare workers. Our protocol allowed for all associated healthcare workers to continue their routine clinical work and daily life. It guaranteed safe return to general patient care without any related complications or nosocomial transmission during the MERS and COVID-19 outbreaks. CONCLUSION: Our protocol and experience with tracheostomies for MERS and COVID-19 may be helpful to other healthcare workers in building an institutional protocol optimized for their own COVID-19 situation.

Severe Thrombocytopenia in a Patient with COVID-19.

Coronavirus disease 2019 (COVID-19) outbreak is spreading rapidly all over the world, being a major threat to public health. Since clinical feature of COVID-19 has not been fully evaluated yet, empirical antibacterial agents are frequently combined for the treatment of COVID-19 in addition to antiviral agents, concerning co-existing bacterial pathogens. We experienced a case of severe thrombocytopenia with epistaxis and petechiae, while treating a COVID-19 patient with ceftriaxone, levofloxacin, and lopinavir/ritonavir. The platelet count decreased to 2,000/mm³ and recovered after discontinuation of the three suspected drugs. In treating a potentially fatal emerging infectious disease, empirical and/or experimental approach would be unavoidable. However, the present case suggests that the possibility of adverse effects caused by polypharmacy should also be carefully considered.

Drive-Through Screening Center for COVID-19: a Safe and Efficient Screening System against Massive Community Outbreak.

As the coronavirus disease 2019 (COVID-19) outbreak is ongoing, the number of individuals to be tested for COVID-19 is rapidly increasing. For safe and efficient screening for COVID-19, drive-through (DT) screening centers have been designed and implemented in Korea. Herein, we present the overall concept, advantages, and limitations of the COVID-19 DT screening centers. The steps of the DT centers include registration, examination, specimen collection, and instructions. The entire service takes about 10 minutes for one testee without leaving his or her cars. Increased testing capacity over 100 tests per day and prevention of cross-infection between testees in the waiting space are the major advantages, while protection of staff from the outdoor atmosphere is challenging. It could be implemented in other countries to cope with the global COVID-19 outbreak and transformed according to their own situations.

Nano- And Microfiber-Based Fully Fabric Triboelectric Nanogenerator For Wearable Devices.

The combination of the triboelectric effect and static electricity as a triboelectric nanogenerator (TENG) has been extensively studied. TENGs using nanofibers have advantages such as high surface roughness, porous structure, and ease of production by electrospinning; however, their shortcomings include high-cost, limited yield, and poor mechanical properties. Microfibers are produced on mass scale at low cost; they are solvent-free, their thickness can be easily controlled, and they have relatively better mechanical properties than nanofiber webs. Herein, a nano- and micro-fiber-based TENG (NMF-TENG) was fabricated using a nylon 6 nanofiber mat and melt blown nonwoven polypropylene (PP) as triboelectric layers. Hence, the advantages of nanofibers and microfibers are maintained and mutually complemented. The NMF-TENG was manufactured by electrospinning nylon 6 on the nonwoven PP, and then attaching Ni coated fabric electrodes on the top and bottom of the triboelectric layers. The morphology, porosity, pore size distribution, and fiber diameters of the triboelectric layers were investigated. The triboelectric output performances were confirmed by controlling the pressure area and basis weight of the nonwoven PP. This study proposes a low-cost fabrication process of NMF-TENGs with high air-permeability, durability, and productivity, which makes them applicable to a variety of wearable electronics.

Infection Prevention Measures for Surgical Procedures during a Middle East Respiratory Syndrome Outbreak in a Tertiary Care Hospital in South Korea.

In 2015, we experienced the largest in-hospital Middle East respiratory syndrome (MERS) outbreak outside the Arabian Peninsula. We share the infection prevention measures for surgical procedures during the unexpected outbreak at our hospital. We reviewed all forms of related documents and collected information through interviews with healthcare workers of our hospital. After the onset of outbreak, a multidisciplinary team devised institutional MERS-control guidelines. Two standard operating rooms were converted to temporary negative-pressure rooms by physically decreasing the inflow air volume (-4.7 Pa in the main room and -1.2 Pa in the anteroom). Healthcare workers were equipped with standard or enhanced personal protective equipment according to the MERS-related patient's profile and symptoms. Six MERS-related patients underwent emergency surgery, including four MERS-exposed and two MERS-confirmed patients. Negative conversion of MERS-CoV polymerase chain reaction tests was noticed for MERS-confirmed patients before surgery. MERS-exposed patients were also tested twice preoperatively, all of which were negative. All operative procedures in MERS-related patients were performed without specific adverse events or perioperative MERS transmission. Our experience with setting up a temporary negative-pressure operation room and our conservative approach for managing MERS-related patients can be referred in cases of future unexpected MERS outbreaks in non-endemic countries.

Efficacy of inhaled ciprofloxacin agents for the treatment of bronchiectasis: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The efficacy of inhaled ciprofloxacin agents in the treatment of patients with bronchiectasis is controversial. The objective of the study was to review systematically the efficacy of inhaled ciprofloxacin agents in patients with bronchiectasis. METHODS: We searched PubMed, EMBASE, and Cochrane Library databases for randomized controlled trials (RCTs) evaluating inhaled ciprofloxacin agents among patients with bronchiectasis. Data were pooled using a meta-analysis technique. RESULTS: Two phase II and four phase III RCTs were included with a total of 1685 patients. Treatment durations of phase III studies were 48 weeks, while those of phase II studies were shorter. Pooled analysis of overall studies exhibited a statistically significant benefit of inhaled ciprofloxacin agents in three exacerbation outcome measures, including time to first exacerbation (hazard ratio 0.74, 95% confidence interval [CI] 0.63-0.86, I2 23%), exacerbation frequency (risk ratio [RR] 0.73, 95% CI 0.61-0.86, I2 42%), and exacerbation proportion (RR 0.85, 95% CI 0.76-0.96, I2 25%) without significant heterogeneity. Outcomes evaluating pulmonary function, quality of life, and adverse events were not significantly different between the two groups. Although eradication of respiratory pathogens was more frequently observed, the emergence of ciprofloxacin resistance was also significantly higher in the ciprofloxacin group. CONCLUSIONS: A meta-analysis of RCTs of inhaled ciprofloxacin agents showed clinical benefit in terms of pulmonary exacerbations in patients with bronchiectasis. Since a significant increase of resistance was also noticed, clinical trials with a longer study period are required for a conclusive assessment. The reviews of this paper are available via the supplemental material section.

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.