Risk Factors for the Prescription of Ineffective Antiviral Candidates for COVID-19 During the Early Pandemic Period in Korea.

BACKGROUND: Although the evidence of treatment for coronavirus disease 2019 (COVID-19) changed rapidly, little is known about the patterns of potential pharmacological treatment during the early period of the COVID-19 pandemic in Korea and the risk factors for ineffective prescription. METHODS: Using claims data from the Korean National Health Insurance System, this retrospective cohort study included admission episodes for COVID-19 from February to December 2020. Ineffective antiviral prescriptions for COVID-19 were defined as lopinavir/ritonavir (LPN/r) and hydroxychloroquine (HCQ) prescribed after July 2020, according to the revised National Institute of Health COVID-19 treatment guidelines. Factors associated with ineffective prescriptions, including patient and hospital factors, were identified by multivariate logistic regression analysis. RESULTS: Of the 15,723 COVID-19 admission episodes from February to June 2020, 4,183 (26.6%) included prescriptions of LPN/r, and 3,312 (21.1%) included prescriptions of HCQ. Of the 48,843 admission episodes from July to December 2020, after the guidelines were revised, 2,258 (4.6%) and 182 (0.4%) included prescriptions of ineffective LPN/r and HCQ, respectively. Patient factors independently associated with ineffective antiviral prescription were older age (adjusted odds ratio [aOR] per 10-year increase, 1.17; 95% confidence interval [CI], 1.14-1.20) and severe condition with an oxygen requirement (aOR, 2.49; 95% CI, 2.24-2.77). The prescription of ineffective antiviral drugs was highly prevalent in primary and nursing hospitals (aOR, 40.58; 95% CI, 31.97-51.50), public sector hospitals (aOR, 15.61; 95% CI, 12.76-19.09), and regions in which these drugs were highly prescribed before July 2020 (aOR, 10.65; 95% CI, 8.26-13.74). CONCLUSION: Ineffective antiviral agents were prescribed to a substantial number of patients during the first year of the COVID-19 pandemic in Korea. Treatment with these ineffective drugs tended to be prolonged in severely ill patients and in primary and public hospitals.

Efficacy of Intranasal Administration of the Recombinant Endolysin SAL200 in a Lethal Murine Staphylococcus aureus Pneumonia Model.

SAL200 is derived from a phage endolysin and is a novel candidate drug for the treatment of Staphylococcus aureus infection. We investigated the efficacy of the recombinant endolysin SAL200 in a lethal murine pneumonia model. Lethal pneumonia was established by intranasally administering a methicillin-susceptible (Newman) or methicillin-resistant (LAC) S. aureus strain into BALB/c mice. The mice were treated with a single intranasal administration of SAL200 or phosphate-buffered saline at 2 h after S. aureus infection. The survival rates were recorded until 60 h after the bacterial challenge. The bacterial loads in the lungs and blood, histopathology of lung tissues, and serum cytokine levels were evaluated following the S. aureus challenge. The SAL200-treated group and control group exhibited 90% to 95% and 10% to 40% survival rates, respectively. The bacterial loads in the lungs of the SAL200-treated group were significantly lower by ∼10-fold than those of the control group as early as 1 h after treatment. Histopathologic recovery of pneumonia was observed in the SAL200-treated mice. The cytokine levels were comparable between groups. These results suggest that direct administration of SAL200 into the lungs could be a potential adjunct treatment against severe pneumonia caused by S. aureus.

A Prospective Cohort Study of Durations of Staphylococcus aureus Bacteremia According to Different Phenotypes and a New Concept of Persistent Bacteremia.

The purpose of this study was to describe and compare the duration of Staphylococcus aureus bacteremia (SAB) according to methicillin resistance and the primary foci of infection. We also aimed to newly define persistent SAB considering these results. Nonduplicated episodes of SAB in patients aged ≥15 years from 14 hospitals in the Republic of Korea were analyzed between January 2009 and February 2018. The duration of SAB was defined as the number of days from the time of administration of an antibiotic to which the isolate was susceptible after the onset of SAB to the last day of a positive blood culture for S. aureus SAB durations were described and compared based on methicillin resistance and the primary foci of infection. Cases in the top quartile for the duration of bacteremia in the respective clinical context were classified as newly defined persistent SAB, and its association with in-hospital mortality was evaluated. A total of 1,917 cases were analyzed. The duration of SAB was longer in patients with methicillin-resistant SAB (MRSAB; n = 995) than in patients with methicillin-susceptible SAB (MSSAB; n = 922) (median duration, 1 day [interquartile range, 1 to 3 days] for MSSAB and 1 day [interquartile range, 0 to 5 days] for MRSAB; P < 0.001). The duration of bacteremia was longer in patients with endocarditis and bone and joint, endovascular, and surgical site infections and was shorter in patients with skin and soft tissue infections. Newly defined persistent SAB was independently associated with in-hospital mortality (adjusted odds ratio, 1.97; 95% confidence interval, 1.54 to 2.53; P < 0.001). The durations of SAB were dependent on methicillin resistance and the primary foci of infection, and considering these contexts, persistent SAB was significantly associated with in-hospital mortality.

Effects of Phage Endolysin SAL200 Combined with Antibiotics on Staphylococcus aureus Infection.

Phages and their derivatives are increasingly being reconsidered for use in the treatment of bacterial infections due to the rising rates of antibiotic resistance. We assessed the antistaphylococcal effect of the endolysin SAL200 in combination with standard-of-care (SOC) antibiotics. The activity of SAL200 when it was combined with SOC antibiotics was assessed in vitro by checkerboard and time-kill assays and in vivo with murine bacteremia and Galleria mellonella infection models. SAL200 reduced the SOC antibiotic MICs and showed a ≥3-log10-CFU/ml reduction of Staphylococcus aureus counts within 30 min in time-kill assays. Combinations of SAL200 and SOC antibiotics achieved a sustained decrease of >2 log10 CFU/ml. SAL200 significantly lowered the blood bacterial density within 1 h by >1 log10 CFU/ml in bacteremic mice (P < 0.05 versus untreated mice), and SAL200 and SOC antibiotic combinations achieved the lowest levels of bacteremia. The bacterial density in splenic tissue at 72 h postinfection was the lowest in mice treated with SAL200 and SOC antibiotic combinations. SAL200 combined with SOC antibiotics also improved Galleria mellonella larva survival at 96 h postinfection. The combination of the phage endolysin SAL200 with SOC antistaphylococcal antibiotics showed synergistic effects in vitro and in vivo The combination of SAL200 with SOC antibiotics could help in the treatment of difficult-to-treat S. aureus infections.

agr dysfunction affects staphylococcal cassette chromosome mec type-dependent clinical outcomes in methicillin-resistant Staphylococcus aureus bacteremia.

Staphylococcal cassette chromosome mec element (SCCmec) type-dependent clinical outcomes may vary due to geographical variation in the presence of virulence determinants. We compared the microbiological factors and mortality attributed to methicillin-resistant Staphylococcus aureus (MRSA) bacteremia between SCCmec types II/III and type IV. All episodes of MRSA bacteremia in a tertiary-care hospital (South Korea) over a 4.5-year period were reviewed. We studied the microbiological factors associated with all blood MRSA isolates, including spa type, agr type, agr dysfunction, and the genes for Panton-Valentine leukocidin (PVL) and phenol-soluble modulin (PSM)-mec, in addition to SCCmec type. Of 195 cases, 137 involved SCCmec types II/III, and 58 involved type IV. The mortality attributed to MRSA bacteremia was less frequent among the SCCmec type IV (5/58) than that among types II/III (39/137, P = 0.002). This difference remained significant when adjusted for clinical factors (adjusted odds ratio [aOR], 0.14; 95% confidence interval [CI], 0.04 to 0.49; P = 0.002). Of the microbiological factors tested, agr dysfunction was the only significant factor that showed different positivity between the SCCmec types, and it was independently associated with MRSA bacteremia-attributed mortality (aOR, 4.71; 95% CI, 1.72 to 12.92; P = 0.003). SCCmec type IV is associated with lower MRSA bacteremia-attributed mortality than are types II/III, which might be explained by the high rate of agr dysfunction in SCCmec types II/III in South Korea.

Impact of medical waste bin on contamination of patient's environment: An experimental study.

BACKGROUND: Medical waste bins are a potential source of microbial contamination in the hospital environment, while there is no clear guidance for the management of them. We aimed to assess the impact of medical waste bins on patient's environment. METHODS: This experimental study simulated microbial contamination by performing medical procedures on a patient model with fluorescent lotion. The waste bin was set as initially empty or two-thirds filled with waste, open or with a lid. The percentage of fluorescent-contaminated area in designated patient's environments was analyzed by 2 independent observers. RESULTS: Among a total of 120 experiments, the sides of the bins were more contaminated in open-occupied bins compared to open-empty bins and in open-occupied bins compared to lid-occupied bins (median 1.9175% vs 0.0916% [P = .001] and 1.9175% vs 0.0899% [P = .003], respectively). The top of the bedside equipment trolley for preparing medical procedures was more contaminated in lid-occupied bins than open-occupied bins (median 0.0080% vs 0.0040%, P = .013). DISCUSSION: In addition to reducing contamination of the bin itself, the manually operated lid had a potential risk of contributing to microbial transmission by contaminating the equipment trolley. CONCLUSIONS: Medical waste bins should be kept no more than two-thirds full, and caution should be taken when using the manually operated lid, to avoid cross-contamination.

Severe Fever with Thrombocytopenia Syndrome in South Korea, 2016-2021: Clinical Features of Severe Progression and Complications.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infection with a high case fatality rate. The serious clinical features need to be further defined. We performed a retrospective analysis among SFTS patients in South Korea during 2016-2021 to update the current status. The basic epidemiology of all reported cases was analyzed, and the detailed clinical data of the subjects were further collected from study hospitals selected in terms of their geographic location and capability of SFTS care. Cases of SFTS were reported across the country and were greatly increased since the initial endemic phase, even under the passive surveillance system. The case fatality rate remained at approximately 16.8%. Coinfections at admission were present in 7.8% of the patients. Major complications included bleeding (15.2%), hemophagocytic lymphohistiocytosis (6.7%), bacteremia or candidemia (4.0%), and invasive pulmonary aspergillosis (1.7%). It took a median 4 days from the onset of illness to hospital admission. Rapid clinical deterioration was observed with a median 1 day for intensive care unit admission, 3 days for mechanical ventilation, 4 days for renal replacement therapy, and 5 days for death, all after the hospitalization. Multivariate analysis showed that the fatality was associated with older age, bacteremia, or candidemia during hospitalization, and the presence of several variables at admission such as fever, altered mentality, aspartate aminotransferase >200 IU/L, serum creatinine level >1.2 mg/dL, and prolonged prothrombin time and activated partial thromboplastin time. Treatment options to improve clinical outcomes are limited, despite best supportive care. Specific treatment is urgently needed to change the fatal course.

Limited impact of bacterial virulence on early mortality risk factors in Acinetobacter baumannii bacteremia observed in a Galleria mellonella model.

Acinetobacter baumannii (AB) has emerged as a major pathogen in vulnerable and severely ill patients. It remains unclear whether early mortality (EM) due to AB bacteremia is because of worse clinical characteristics of the infected patients or the virulence of the pathogen. In this study, we aimed to investigate the effect of AB virulence on EM due to bacteremia. This retrospective study included 138 patients with AB bacteremia (age: ≥ 18 years) who were admitted to a tertiary care teaching hospital in South Korea between 2015 and 2019. EM was defined as death occurring within 7 days of bacteremia onset. The AB clinical isolates obtained from the patients' blood cultures were injected into 15 Galleria mellonella larvae each, which were incubated for 5 days. Clinical isolates were classified into high- and low-virulence groups based on the number of dead larvae. Patients' clinical data were combined and subjected to multivariate Cox regression analyses to identify the risk factors for EM. In total, 48/138 (34.8%) patients died within 7 days of bacteremia onset. The Pitt bacteremia score was the only risk factor associated with EM. In conclusion, AB virulence had no independent effect on EM in patients with AB bacteremia.

Can a routine follow-up blood culture be justified in Klebsiella pneumoniae bacteremia? A retrospective case-control study.

BACKGROUND: The need for mandatory confirmation of negative conversion in Klebsiella pneumoniae bacteremia (KpB) has not been adequately addressed. We conducted a retrospective case-control study of adult patients with KpB over a 5-year period in two tertiary-care hospitals to determine the risk factors for persistent bacteremia and to reevaluate the necessity of follow-up blood culture in KpB. METHODS: Persistent KpB is defined as the finding of K. pneumoniae in more than two separate blood-culture samples for longer than a two-day period in a single episode. The case- and control-groups were patients with persistent and non-persistent KpB, respectively, and they were matched 1-to-3 according to age and gender. RESULTS: Among 1068 KpB episodes analyzed after excluding polymicrobial infection and repeated KpB, follow-up blood cultures were performed in 862 cases (80.7%), 62 of which (7.2%) were persistent. Independent risk factors for persistence were intra-abdominal infection, higher Charlson's comorbidity weighted index score, prior solid organ transplantation, and unfavorable treatment response, which was defined as positivity for at least two parameters among fever, leukocytosis, and no decrease of C-reactive protein on the second day after initial culture. A proposed scoring system using four variables, namely, intra-abdominal infection, nosocomial KpB, fever and lack of C-reactive protein decrease, the last two being assessed on the second day after the initial blood culture, showed that only 4.9% of the patients with no risk factors or with only intra-abdominal infection had persistent KpB. CONCLUSIONS: Though persistent KpB is uncommon, follow-up blood culture was performed in as many as 80% of the cases in this study. A more careful clinical assessment is warranted to reduce the cost and patient inconvenience involved in follow-up blood culture.

Mortality After Acute Coronary Syndrome in Human Immunodeficiency Virus Infection with Optimal Adherence: A Nationwide Study.

BACKGROUND: There have been few studies on the outcome of acute coronary syndrome (ACS) in human immunodeficiency virus (HIV) infection in the era when antiretroviral therapy (ART) is generalized and most of them have achieved viral suppression. Using claims data, we aimed to assess the mortality after atherosclerotic cardiovascular events in people with HIV (PWH) who maintain optimal adherence to ART. MATERIALS AND METHODS: We used claims data from the National Health Insurance of the Korea to confirm newly diagnosed PWH from 2009 to 2019, and measured ART adherence. ACS and mortality were confirmed in PWH who showed optimal adherence to ART. RESULTS: Among 7,100 PWH with optimal adherence and during 27,387 person-year of follow-up duration, ACS was confirmed in 140 (2.0%) cases, which was 1.3 times greater than statistics of the Korean general population (511.0 vs. 383.1 per 100,000). Acquired immunodeficiency syndrome, hypertension, dyslipidemia, and diabetes mellitus were associated with the development of ACS in PWH with optimal adherence. Mortality was confirmed in 10 cases, which is 7.1% overall and 2.9% when limited to myocardial infarction. It was comparable with the mortality rate of the Korean general population after myocardial infarction (8.9%). CONCLUSION: ACS prevalence was higher in PWH even when optimal adherence was maintained. However, mortality after ACS was comparable to that in the HIV-negative population.

Resistance Trends of Antiretroviral Agents in People with Human Immunodeficiency Virus in Korea, 2012 - 2020.

BACKGROUND: Domestic data on antiretroviral drug (ARV) resistance are limited, while alterations in ARV resistance are expected as the incidence of human immunodeficiency virus (HIV) infection increases. We evaluated the ten-year change in ARV resistance in people with HIV (PWH) in Korea. MATERIALS AND METHODS: Adults aged ≥19 years and diagnosed with HIV infection between January 2010 and December 2020 at a 750-bed municipal hospital were retrospectively reviewed. Data on clinical characteristics and resistance mutation test results were collected. The study population was divided into three-year intervals according to diagnosed year and their clinical characteristics were compared. RESULTS: A total of 248 PWH were analyzed, and ARV resistance was detected in 30 of them (12.1%). Resistance was detected most frequently in PWH aged ≤29 years (16, 6.5%), and the median percentage of resistance detection per year was 14.3% (interquartile range, 12.7 - 16.1). The trend of the overall prevalence of ARV resistance mutations slightly decreased and then increased over time (15.3% in 2012 - 2014, 9.6% in 2015 - 2017, and 12.9% in 2018 - 2020). The prevalence of the non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance markedly decreased over time (15.3% in 2012 - 2014, 8.7% in 2015 - 2017, and 2.4% in 2018-2020), while that of protease inhibitor (PI) and integrase strand transfer inhibitor (INSTI) increased from 0 until 2018 to 3.5% and 8.2% in 2018 - 2020, respectively. CONCLUSION: The trend of NNRTI resistance has decreased over time, and resistance to PIs and INSTIs increased from 2018. Therefore, continuous monitoring of ARV resistance pattern is necessary.

Outbreak of carbapenem-resistant Enterobacterales at a long-term care facility in Seoul, Korea: surveillance and intervention mitigation strategies.

OBJECTIVES: Because effective decolonization options are not available, and treatment options are limited, carbapenem-resistant Enterobacterales (CRE) constitute increasingly threatening nosocomial pathogens. To prevent CRE-associated transmission and ensure patient safety, healthcare personnel and everyone in contact with CRE-infected patients must implement stringent infection control practices. This report describes a CRE outbreak, possibly related to a caregiver at a long-term care facility (LTCF), and presents a new surveillance model to improve the infection control of CRE in Seoul, Korea. METHODS: The Seoul Metropolitan Government surveillance system identified an outbreak of CRE in an LTCF in 2022. We obtained data on the demographic characteristics and contact histories of the inpatients, medical staff, and caregivers. To isolate the inpatients and employees exposed to CRE, we used rectal swab samples and environmental sampling during the study period (May-December 2022). RESULTS: We identified 18 cluster cases (1 caregiver and 17 inpatients) and 12 sporadic cases with CRE, and conducted a complete 197-day follow-up of all cases in the LTCF's isolation wards. CONCLUSIONS: This investigation demonstrated that our surveillance model and targeted intervention, based on the cooperation of the municipal government, public health center, and infection control advisory committee, effectively contained the epidemic at the LTCF. Measures to improve the compliance of all employees in LTCFs with infection control guidelines should also be adopted.

Possibility of Decreasing Incidence of Human Immunodeficiency Virus Infection in Korea.

BACKGROUND: The number of newly diagnosed cases of human immunodeficiency virus (HIV) infection in Korea, which had increased until 2019, has markedly decreased since the coronavirus disease 2019 pandemic started. This study evaluated whether the decrease is due to a reduction in the incidence of HIV infection and/or delayed diagnosis during the pandemic. MATERIALS AND METHODS: We reviewed the medical records of 587 newly diagnosed patients with HIV infection between February 2018 and January 2022 from four general hospitals, and their characteristics were compared between the pre-pandemic and pandemic periods. The lapse time from infection to diagnosis was estimated using an HIV modeling tool. RESULTS: The estimated mean times to diagnosis were 5.68 years (95% confidence interval [CI]: 4.45 - 6.51 years) and 5.41 years (95% CI: 4.09 - 7.03 years) before and during the pandemic, respectively (P = 0.016). The proportion of patients with acquired immunodeficiency syndrome-defining illnesses, expected to visit hospitals regardless of the pandemic, decreased from 17.2% before the pandemic to 11.9% during the pandemic (P = 0.086). CONCLUSION: The decrease in the number of newly diagnosed cases of HIV infection in Korea might have resulted from an actual decrease in the incidence of HIV infection rather than a worsening of underdiagnosis or delayed diagnosis.

Different levels of humoral and cellular immunity to varicella-zoster virus in seropositive healthcare workers.

BACKGROUND: There have been occasional reports on varicella infection among healthcare workers (HCWs) despite varicella-zoster virus (VZV) seropositivity. We compared the levels of humoral and cellular immunity to VZV in seropositive HCWs who had acquired immunity by natural infection or vaccination. METHODS: Seropositive healthy HCWs with an apparent history of varicella or VZV vaccination once or twice were recruited. Their samples were assessed for anti-VZV IgG levels, the relative avidity index (RAI), and the frequencies of VZV-specific cytokine-producing or polyfunctional CD4+ or CD8+ T cells. RESULTS: A total of 75 seropositive HCWs (29 with a history of varicella, 25 vaccinated once, and 21 vaccinated twice) were assessed for humoral immunity. Cellular responses could be analyzed in 59 (28, 21, and 10 in the respective groups). The anti-VZV IgG level, RAI, and memory CD4+ T cell responses were significantly higher in the past infection group than in the vaccinated once group. The RAI levels were significantly higher in the past infection group than in the vaccinated twice group. CONCLUSION: Seropositive HCWs without a varicella history, especially those who received the vaccine only once, had significantly lower levels of immune responses to VZV. Such HCWs might need to comply with airborne precautions.

Clinical and economic burden of bacteremia due to multidrug-resistant organisms in Korea: a prospective case control study.

OBJECTIVES: The socioeconomic and clinical burden of multidrug-resistant organisms (MDRO), including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), multidrug-resistant Acinetobacter baumannii (MRAB), multidrug-resistant Pseudomonas aeruginosa (MRPA), and carbapenem-resistant Enterobacteriaceae (CRE) have not yet been adequately addressed. METHODS: We prospectively searched for MDRO bacteremia cases with matched controls from 10 hospitals across Korea during a 6-month period in 2017. Patients were classified into the MDRO, susceptible organism, and no-infection groups. The corresponding susceptible or no-infection controls had been selected according to predefined criteria. We collected clinical information and estimated the total additional medical cost due to MDRO infections using the multistate model. RESULTS: During the 6-month period, a total of 486 MDRO bacteremia cases (260, 87, 18, 20, and 101 cases of MRSA, MRAB, MRPA, CRE, and VRE, respectively) were identified. The 90-d mortality rates were 30.4%, 63.2%, 16.7%, 55.0%, and 47.5%, respectively. The additional costs caused by bacteremia were $15 768, $35 682, $39 908, $72 051, and $33 662 per MDRO type, respectively. Based on these 6-month data, the estimated annual number of bacteremia cases due to these five MDRO in Korea were 7979 (4070, 1396, 218, 461, and 1834 cases, respectively). Overall, this caused an estimated 3280 (1237, 882, 36, 254, and 871, respectively) deaths and cost $294 505 002 ($84 707 359, $74 387 364, $10 344 370, $45 850 215, and $79 215 694, respectively) (range $170,627,020-$416,094,679) in socioeconomic loss. CONCLUSIONS: A tremendous clinical and economic burden is caused by MDRO bacteremia compared with antibiotic-susceptible and no-infection groups. Substantial investment and efforts by related government agencies and medical staffs are needed.

Socioeconomic burden of pneumonia due to multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa in Korea.

We aimed to estimate the socioeconomic burden of pneumonia due to multidrug-resistant Acinetobacter baumannii (MRAB) and Pseudomonas aeruginosa (MRPA). We prospectively searched for MRAB and MRPA pneumonia cases and matched them with susceptible-organism pneumonia and non-infected patients from 10 hospitals. The matching criteria were: same principal diagnosis, same surgery or intervention during hospitalisation, age, sex, and admission date within 60 days. We calculated the economic burden by using the difference in hospital costs, the difference in caregiver costs, and the sum of productivity loss from an unexpected death. We identified 108 MRAB pneumonia [MRAB-P] and 28 MRPA pneumonia [MRPA-P] cases. The estimated number of annual MRAB-P and MRPA-P cases in South Korea were 1309-2483 and 339-644, with 485-920 and 133-253 deaths, respectively. The annual socioeconomic burden of MRAB-P and MRPA-P in South Korea was $64,549,723-122,533,585 and $15,241,883-28,994,008, respectively. The results revealed that MRAB-P and MRPA-P occurred in 1648-3127 patients, resulted in 618-1173 deaths, and caused a nationwide socioeconomic burden of $79,791,606-151,527,593. Multidrug-resistant organisms (MDRO) impose a great clinical and economic burden at a national level. Therefore, controlling the spread of MDRO will be an effective measure to reduce this burden.

Short course of voriconazole therapy as a risk factor for relapse of invasive pulmonary aspergillosis.

To investigate associations of the duration of voriconazole treatment and radiological response with relapse of invasive pulmonary aspergillosis (IPA) in immunocompromised patients, we explored the risk factors for IPA relapse after successful initial treatment. All patients with proven or probable IPA who had finished voriconazole treatment between 2005 and 2019 in a tertiary-care hospital were reviewed. IPA relapse was defined as re-diagnosis of proven or probable IPA at the same site within 1 year after treatment termination. Short course of voriconazole treatment was defined as a treatment less than 9 weeks, which is a median of the recommended minimum duration of therapy from the Infectious Disease Society of America. The radiological response was defined as a reduction in IPA burden by more than 50% on chest computed tomography. Of 87 patients who had completed voriconazole treatment, 14 (16.1%) experienced IPA relapse. Multivariable Cox regression identified that short voriconazole treatment duration (adjusted hazard ratio [aHR], 3.7; 95% confidence interval [CI], 1.1-12.3; P = 0.033) and radiological non-response (aHR, 4.6; 95% CI, 1.2-17.5; P = 0.026) were independently associated with relapse of IPA after adjusting for several clinical risk factors. Longer duration of therapy should be considered for those at higher risk of relapse.

Differences in characteristics between first and breakthrough neutropenic fever after chemotherapy in patients with hematologic disease.

OBJECTIVE: This study was conducted to compare the clinical and microbiological characteristics of first and breakthrough neutropenic fever in hematologic malignancy patients after chemotherapy. METHODS: Breakthrough neutropenic fever was any episode of fever, not present initially, that developed either during antibiotic therapy or within 1 week of discontinuation of therapy. A total of 687 neutropenic fever episodes in 241 patients were observed from April 2003 to March 2014. RESULTS: Blood cultures revealed 210 causative microorganisms: 199 (94.8%) were bacteria and 11 (5.2%) were fungi. Gram-negative bacteria predominated in both types of neutropenic episode (first 75% (120/160) vs. breakthrough 56% (18/32)) and the most common pathogen was Escherichia coli. Antibiotic resistance rates were higher in breakthrough episodes than first episodes (piperacillin/tazobactam 6% vs. 31%, p=0.006; ceftazidime 9% vs. 31%, p=0.025). Inappropriate empirical antibiotic treatment was also more frequent (0% vs. 19%, p=0.001), as was the 30-day mortality rate (4.3% (19/442) vs. 7.9% (19/245), p=0.058), although the latter effect was not statistically significant. CONCLUSION: It is concluded that the epidemiological profile of breakthrough neutropenic fever is different from that of first episode fever. These data reinforce the view that pooled reporting of neutropenic fever may be misleading, and that clinicians should approach breakthrough fever as a distinct entity.

Impact of the multiplex polymerase chain reaction in culture-positive samples on appropriate antibiotic use in patients with staphylococcal bacteremia.

Rapid identification of the microorganisms in patients with bacteremia may be useful in clinical practice. We evaluated the impact of the multiplex polymerase chain reaction (PCR) on appropriate antibiotic use for patients with gram-positive cocci cluster (GPCC) bacteremia. We divided the GPCC bacteremia cases into a pre-PCR group (2010-2011) and a post-PCR group (2012-2013). A total 664 cases were included in the pre-PCR group; and 570, in the post-PCR group. In methicillin-susceptible Staphylococcus aureus (MSSA) cases, optimal antibiotics were administered earlier in the post-PCR group (77.4h versus 42.6h, P=0.035). Although the proportions of glycopeptide exposure did not differ (54.7% versus 56.7%, P=0.799), the duration of exposure decreased (69.6h versus 30.7h, P=0.004). In methicillin-resistant S. aureus cases, the time to optimal antibiotics administration did not differ (45.4h versus 43.7h, P=0.275). Multiplex PCR test significantly improved the early initiation of optimal antibiotics in MSSA bacteremia and reduced the unnecessary glycopeptide exposure.