Evaluation of Two Commercial Kits for Qualitative Detection of SARS-CoV-2 Antigens in Nasopharyngeal Specimens.

BACKGROUND: Two rapid antigen tests (RATs) for COVID-19 targeting the nucleocapsid protein of SARS-CoV-2 were compared with real-time RT-PCR as the reference method. METHODS: Ninety-six nasopharyngeal swab samples, comprising 56 positive and 40 negative samples confirmed through rRT-PCR were collected and retested to determine the reliability of the two nasopharyngeal RATs. RESULTS: The overall sensitivity and specificity of both RATs were 64.3% (95% confidence interval 50.4 - 76.6%) and 100% (95% confidence interval 91.2 - 100%), respectively. Cohen's kappa coefficient of agreement of both RATs to rRT-PCR was 0.600 (95% confidence interval 0.457 - 0.743) (p < 0.001), showing almost perfect agreement when the Ct values were less than 25 in rRT-PCR. A significant difference in Ct values between true positives and false negatives was observed (Mann-Whitney-Wilcoxon test; p < 0.001). CONCLUSIONS: Compared to rRT-PCR, RATs have fewer false negatives. In suspected COVID-19 cases, negative RAT results should be retested using either RAT or rRT-PCR.

Augmented humoral and cellular immunity against severe acute respiratory syndrome coronavirus 2 after breakthrough infection in kidney transplant recipients who received 3 doses of coronavirus disease 2019 vaccine.

Diminished immune response to coronavirus disease 2019 (COVID-19) vaccines and breakthrough infection (BI) is a major concern for solid organ transplant recipients. Humoral and cellular immune responses of kidney transplant (KT) recipients after a third COVID-19 vaccination were investigated compared to matched health care workers. Anti-severe acute respiratory syndrome coronavirus 2 spike protein antibody and severe acute respiratory syndrome coronavirus 2 specific interferon-gamma releasing assay (IGRA) were assessed. A total of 38 KT recipients, including 20 BI and 18 noninfection, were evaluated. In the KT BI group, antibody titers were significantly increased (median 5 to 724, binding antibody units/mL (P = 0.002) after the third vaccination, but IGRA responses were negligible. After BI, antibody titers increased (median 11 355 binding antibody unit/mL; P < 0.001) and there was a significant increase of IGRA responses to spike proteins (Spike1-Nil, median 0.05 to 0.41 IU/mL; P = 0.009). Antibody titers and IGRA responses were significantly higher in the BI than in the noninfection group after 6 months. Immune responses were stronger in the health care worker than in the KT cohort, but the gap became narrower after BI. In conclusion, KT recipients who experienced BI after 3 COVID-19 vaccinations acquired augmented humoral and cellular immune responses.

Triple immune modulator therapy for aberrant hyperinflammatory responses in severe COVID-19.

A dysregulated hyperinflammatory response is a key pathogenesis of severe COVID-19, but optimal immune modulator treatment has not been established. To evaluate the clinical effectiveness of double (glucocorticoids and tocilizumab) and triple (plus baricitinib) immune modulator therapy for severe COVID-19, a retrospective cohort study was conducted. For the immunologic investigation, a single-cell RNA sequencing analysis was performed in serially collected PBMCs and neutrophil specimens. Triple immune modulator therapy was a significant factor in a multivariable analysis for 30-day recovery. In the scRNA-seq analysis, type I and II IFN response-related pathways were suppressed by GC, and the IL-6-associated signature was additionally downregulated by TOC. Adding BAR to GC and TOC distinctly downregulated the ISGF3 cluster. Adding BAR also regulated the pathologically activated monocyte and neutrophil subpopulation induced by aberrant IFN signals. Triple immune modulator therapy in severe COVID-19 improved 30-day recovery through additional regulation of the aberrant hyperinflammatory immune response.

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.

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.

Markedly Increased Mean Platelet Volume in Bacterial Meningitis.

BACKGROUND: Differentiating bacterial and viral meningitis is crucial, and this study explored the potential of mean platelet volume (MPV) as a marker for differentiation. METHODS: Blood samples were collected from patients with central nerve system related manifestations, and MPV was tested. Cerebrospinal fluid samples were obtained and bacterial culture and the FilmArray ME panel were performed. The distribution of MPV was compared between groups. RESULTS: The study included 8 patients in the bacterial meningitis group and 12 patients in the viral meningitis group. The bacterial meningitis group showed a significantly higher median MPV of 10.9 (9.2 - 11.6) fL compared to the viral meningitis group with 8.4 (8.1 - 8.8) fL (p < 0.0001). CONCLUSIONS: MPV could serve as a diagnostic indicator to differentiate between bacterial and viral meningitis. Larger studies are needed to validate these findings.

Clinical Utility of Sero-Immunological Responses Against SARS-CoV-2 Nucleocapsid Protein During Subsequent Prevalence of Wild-Type, Delta Variant, and Omicron Variant.

As nucleocapsid protein of severe acute respiratory syndrome coronavirus 2 is immunogenic but not targeted in vaccines, it could be useful in distinguishing natural infection from vaccination. We aimed to investigate the clinical utility of sero-immunological responses against the nucleocapsid protein. Nucleocapsid antibody immunoassay study with 302 coronavirus disease 2019 (COVID-19) patients showed lower titers in immunocompromised patients (P < 0.001), higher titers in higher severity (P = 0.031), and different seroconversion rates and titers according to variants of concern. Longitudinal evaluation of nucleocapsid antibodies using 513 samples from 291 COVID-19 patients revealed that it could persist up to 556 days from symptom onset. Interferon gamma release assay against the nucleocapsid protein showed poor response, precluding the deduction of a cut-off for the nucleocapsid protein. In conclusion, nucleocapsid antibody provides instructive clues about the immunogenicity of nucleocapsid proteins by different seroconversion rates and titers according to the severity of infection, host immune status, and different variants of concern.

Loss of Neutralizing Activity of Tixagevimab/Cilgavimab (Evusheld™) Against Omicron BN.1, a Dominant Circulating Strain Following BA.5 During the Seventh Domestic Outbreak in Korea in Early 2023.

Tixagevimab/cilgavimab is a monoclonal antibody used to prevent coronavirus disease 2019 among immunocompromised hosts and maintained neutralizing activity against early omicron variants. Omicron BN.1 became a dominant circulating strain in Korea early 2023, but its susceptibility to tixagevimab/cilgavimab is unclear. We conducted plaque reduction neutralization test (PRNT) against BN.1 in a prospective cohort (14 patients and 30 specimens). BN.1 PRNT was conducted for one- and three-months after tixagevimab/cilgavimab administration and the average PRNT ND50 of each point was lower than the positive cut-off value of 20 (12.9 ± 4.5 and 13.2 ± 4.2, respectively, P = 0.825). In the paired analyses, tixagevimab/cilgavimab-administered sera could not actively neutralize BN.1 (PRNT ND50 11.5 ± 2.9, P = 0.001), compared with the reserved activity against BA.5 (ND50 310.5 ± 180.4). Unlike virus-like particle assay, tixagevimab/cilgavimab was not active against BN.1 in neutralizing assay, and would not be effective in the present predominance of BA.2.75 sublineages.

Evolution of Fluconazole Resistance Mechanisms and Clonal Types of Candida parapsilosis Isolates from a Tertiary Care Hospital in South Korea.

We investigated the evolution of fluconazole resistance mechanisms and clonal types of Candida parapsilosis isolates from a tertiary care hospital in South Korea. A total of 45 clinical isolates, including 42 collected between 2017 and 2021 and 3 collected between 2012 and 2013, were subjected to antifungal susceptibility testing, sequencing of fluconazole resistance genes (ERG11, CDR1, TAC1, and MRR1), and microsatellite typing. Twenty-two isolates carried Y132F (n = 21; fluconazole MIC = 2 to >256 mg/L) or Y132F+R398I (n = 1; fluconazole MIC = 64 mg/L) in ERG11 and four isolates harbored N1132D in CDR1 (fluconazole MIC = 16 to 64 mg/L). All 21 Y132F isolates exhibited similar microsatellite profiles and formed a distinct group in the dendrogram. All four N1132D isolates displayed identical microsatellite profiles. Fluconazole MIC values of the Y132F isolates varied depending on their MRR1 mutation status (number of isolates, year of isolation, and MIC): K177N (n = 8, 2012 to 2020, 2 to 8 mg/L); K177N + heterozygous G982R (n = 1, 2017, 64 mg/L); K177N + heterozygous S614P (n = 2, 2019 to 2020, 16 mg/L); and K177N + homozygous S614P (n = 10, 2020 to 2021, 64 to > 256 mg/L). Our study revealed that Y132F in ERG11 and N1132D in CDR1 were the major mechanisms of fluconazole resistance in C. parapsilosis isolates. Furthermore, our results suggested that the clonal evolution of Y132F isolates persisting and spreading in hospital settings for several years occurred with the acquisition of heterozygous or homozygous MRR1 mutations associated with a gradual increase in fluconazole resistance.

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.

Poor outcomes of early recurrent post-transplant bloodstream infection in living-donor liver transplant recipients.

Bloodstream infection (BSI) is a common complication after living-donor liver transplantation (LDLT). Some patients develop recurrent BSIs. We evaluated the impacts of early recurrent BSIs (ER-BSIs) on outcomes in LDLT recipients. LDLT cases between 2008 and 2016 were included. Early BSI (E-BSI) was defined as a BSI event that occurred within 2 months after LDLT. ER-BSIs were defined as new-onset BSIs within 2 months due to another pathogen at a ≥ 48-h interval or a relapse of BSIs by the same pathogen at a ≥ 1-week interval, with negative cultures in between. The primary objective was evaluating the all-cause mortality of each group of LDLT recipients (90 days and 1 year). The secondary objectives were analyzing associated factors of each all-cause mortality and risk factors for early single BSI and ER-BSI. Among 727 LDLT recipients, 108 patients experienced 149 events of E-BSI with 170 isolated pathogens. Twenty-eight patients (25.9%, 28/108) experienced ER-BSI. The 1-year survival rates of patients without BSI, with early single BSI event, and with ER-BSIs were 92.4%, 81.3%, and 28.6%, respectively. ER-BSI was the most significant risk factor for 1-year mortality (adjusted HR = 5.31; 95% CI = 2.27-12.40). Intra-abdominal and/or biliary complications and early allograft dysfunction were risk factors for both early single BSI and ER-BSI. Interestingly, longer cold ischemic time and recipient operative time were associated with ER-BSI. LDLT recipients with ER-BSI showed very low survival rates accompanied by intra-abdominal complications. Clinicians should prevent BSI recurrence by being aware of intra-abdominal complications.

Mean Platelet Volume in Pediatric Patients Infected with Mycoplasma pneumoniae.

BACKGROUND: Mean platelet volume (MPV) is a parameter of platelet size and activity. Research on MPV in Mycoplasma pneumoniae infection is not reported. METHODS: This study reviewed whether there was a difference in the MPV in the results of M. pneumoniae immunoglobulin M (IgM) and polymerase chain reaction (PCR) tests in 210 pediatric patients with pneumonia suspected to be caused by M. pneumoniae. RESULTS: The MPV was significantly lower in the IgM-positive group than in the IgM- negative group (p = 0.041). Among the PCR-positive patients (n = 73), the IgM-positive group showed significantly lower MPV than the IgM-negative group (p = 0.014). Meanwhile, among the PCR-negative patients (n = 137), there was no significant difference in the MPV between the IgM-positive and negative groups (p = 0.269). CONCLUSIONS: This result suggests that pneumonia caused by M. pneumoniae could be a condition associated with low MPV.

Can we Predict the Clinical Course of Immune Thrombocytopenia in Children by The Mean Platelet Volume? A Preliminary Study.

BACKGROUND: Mean platelet volume (MPV) is considered a marker of platelet function and is known to increase in immune thrombocytopenia (ITP). We aimed to investigate the predictive value of MPV for predicting the clinical course of ITP in children. METHODS: We retrospectively analyzed children aged < 18 years with ITP (n = 36) and healthy controls (n = 36) from June 2010 to November 2018. The subjects were stratified into: (i) Healthy controls [group I, n = 36]; (ii) Newly diagnosed ITP (nITP) and persistent ITP (pITP) [group II, n = 24]; and (iii) Chronic ITP (cITP) [group III, n = 12]. Hematological indices including MPV were measured and compared between the three groups. RESULTS: The median MPV values at diagnosis in group I, II, and III were 7.20, 8.15, and 8.65 fL, respectively (p = 0.0004). Cutoff value of MPV at diagnosis differentiating group I from group II + III was 7.6 fL, and group II from group III was 8.7 fL. MPV change (ΔMPV after three months minus MPV at diagnosis) in children with nITP and pITP (n = 22) was greater than in those with cITP (n = 6) (-2.18 fL vs. 0.66 fL, p = 0.0059). CONCLUSIONS: This study revealed that group III had a higher MPV than group II at diagnosis. Therefore, an initial MPV value more than 8.7 fL may be used as a predictive factor for chronicity in children with ITP. The change in MPV over time as well as MPV at diagnosis, may be regarded as a prognostic marker to predict the course of ITP in children.

Impact of Difficult-to-Treat Resistance in Gram-negative Bacteremia on Mortality: Retrospective Analysis of Nationwide Surveillance Data.

BACKGROUND: Clinically relevant categorization of antimicrobial resistance is critical to mitigating the threat it poses. Difficult-to-treat resistance (DTR) is a recently proposed category defined as nonsusceptibility to all first-line antibiotic agents. METHODS: A retrospective study was conducted with nonduplicate cases of gram-negative bloodstream infection (GNBSI) caused by 4 major taxa (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter species) identified from a nationwide surveillance database. DTR was defined as nonsusceptibility to all the ß-lactams and fluoroquinolones tested. Patient characteristics and mortality were compared between DTR GNBSI and GNBSI caused by carbapenem-resistant but not DTR and extended-spectrum cephalosporin-resistant but not DTR isolates using Centers for Disease Control and Prevention definitions. Adjusted odds ratios (aORs) for 30-day in-hospital mortality were examined for DTR in overall and in propensity score-matched cohorts. RESULTS: A total of 1167 episodes of monomicrobial GNBSI were identified, and 147 (12.6%) of the isolates were DTR. The majority of DTR isolates were Acinetobacter species (79.6%) and P. aeruginosa (17.7%). DTR infections were associated with previous antibiotic use, healthcare contact, ventilator use, and lower respiratory tract infection. Crude mortality for GNBSI caused by DTR was 50.3%. A multivariable model showed that only DTR, but not other categories, was significantly associated with mortality (adjusted odds ratio [aOR], 3.58 [95% confidence interval {CI}, 1.27-10.19]). DTR was also a significant predictor for mortality in the analysis of propensity score-matched cohorts (aOR, 3.48 [95% CI, 1.82-6.79]). CONCLUSIONS: In patients with GNBSI, DTR was associated with higher mortality than those in other resistance categories. Our findings suggest that DTR could be useful for surveillance and prognostication.

Emergence of vancomycin-resistant Enterococcus faecium ST1421 lacking the pstS gene in Korea.

Although multilocus sequence typing (MLST) has been used to study molecular epidemiology and to explore the population structure of Enterococcus faecium, vancomycin-resistant E. faecium (VREF) strains lacking the pstS gene that were non-typable using conventional MLST methods were reported recently. We found nationwide emergence of VREF isolates lacking pstS in Korea and hereby report the molecular characteristics of these isolates. Forty-six VREF isolates lacking the pstS gene were identified among 300 VREF rectal isolates collected from hospitalized patients between 2014 and 2015. MLST was performed and clonal relatedness was determined by pulsed-field gel electrophoresis (PFGE). Four VREF ST1421 isolates were whole-genome sequenced. Among the VREF rectal isolates lacking pstS, 98% were classified as ST1421, which has identical allelic profiles to ST17 for all housekeeping genes except pstS. PFGE pattern analyses revealed 32 pulsotypes. All isolates harbored Tn1546 components with various transposase and insertion sequences. The whole-genome sequencing of four VREF ST1421 isolates showed that the pstS gene region was deleted at various locations with considerable inversion. The pstS gene was also depleted in 12.1% of 33 VREF clinical isolates in 2006-2007 and in 11.8% of 59 clinical isolates in 2012-2013. VREF ST1421 strains lacking the pstS gene have emerged in Korea. The emergence and spread of pstS-deleted VREF strains pose a serious challenge for epidemiological investigation. Alternative molecular typing methods to MLST will be increasingly necessary.

Clinical factors influencing the performance of bacterial multiplex polymerase chain reaction in patients with community-onset pneumonia.

The etiologic diagnostic yield of community-onset pneumonia (COP) using conventional methods is low. Bacterial multiplex polymerase chain reaction (mPCR) has been shown to be more sensitive than conventional methods. This study assessed the clinical factors influencing bacterial mPCR results in patients with COP. Patients with COP admitted to a tertiary care hospital between November 2015 and April 2016 were retrospectively assessed. Conventional methods included culture-based methods and serology for Mycoplasma pneumoniae. Bacterial mPCR that could identify Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, and Legionella pneumophilia was performed. Bacterial mPCR was performed in a total of 342 patients with COP in the study. Bacterial mPCR alone provided etiology in 99 patients. The total etiologic diagnosis rates improved from 22.2 to 51.1% when bacterial mPCR was added to conventional methods. Additional diagnostic benefits of bacterial mPCR were more prominent in the prior antibiotic non-exposure group (77.8% vs 63.5%, P = 0.015) and in the low-risk group with low CURB 65 score (62.6% vs 44.9%, P = 0.005). Patients who required ICU care, those with healthcare-associated pneumonia (HCAP), and patients with any underlying diseases were not associated with the additional pathogen detection rates using bacterial mPCR. By supplementing conventional diagnostic methods with bacterial mPCR-based methods, the overall pathogen detection rates improved in patients with COP. Moreover, the additional diagnostic usefulness of bacterial mPCR was significantly higher in patients without prior antibiotic exposure and in the mild-to-moderate-risk group with lower CURB 65 score.

Risk factors for development and mortality of invasive pulmonary Aspergillosis in kidney transplantation recipients.

Invasive pulmonary aspergillosis (IPA) is a high mortality opportunistic infection among kidney transplant recipients. This study assessed the risk factors and outcomes of IPA after KT. A retrospective study was conducted at a tertiary-care referral hospital in Korea. Electronic medical records of patients diagnosed with IPA after KT between February 1995 and March 2015 were reviewed. The control patients comprised two patients who received KT before and after each IPA case. Twenty-six cases were diagnosed with IPA among 1963 recipients at a median of 58 years old. The most common cause of end-stage renal disease was diabetic nephropathy. The median time to diagnosis was 161 days. Delayed graft function was associated with the development of IPA. The overall 12-week mortality rate of IPA was 57.5%. Serum GM level ≥ 2 and BAL GM level ≥ 5 were associated with 12-week mortality in the Kaplan-Meier survival analyses. Approximately half of IPA in KT recipients developed during the late posttransplant period (> 6 months), especially after treatment for acute rejection. Careful monitoring for IPA is required in patients with delayed graft function, DM, and who received rejection therapy. Higher serum and BAL GM were associated with 12-week mortality.

Clinical effectiveness of oral antimicrobial therapy for acute pyelonephritis caused by extended-spectrum ß-lactamase-producing Enterobacteriales.

Infections caused by extended-spectrum ß-lactamase-producing Enterobacteriales (ESBL-PE) are commonly treated with intravenous antibiotics. This study investigated whether oral antimicrobial therapy (OAT) is as effective as intravenous antimicrobial therapy (IVT) for acute pyelonephritis (APN) caused by ESBL-PE. A retrospective cohort of patients with APN caused by ESBL-PE was studied at a tertiary-care hospital from January 2014 through December 2016. The OAT group comprised patients treated with an appropriate oral antimicrobial agent following 7 days or less of IVT. The primary endpoint was treatment failure defined as clinical and/or microbiological failure. The secondary endpoint was length of hospital stay and recurrences of APN within 2 months and within 1 year. Propensity score matching and multivariable Cox proportional hazard modeling were used to minimize bias. Among 238 eligible cases, Escherichia coli (83.6%) was the most common pathogen. Sixty patients received OAT after a median of four days of appropriate IVT, and 178 patients completed treatment with IVT. Fluoroquinolones (58.3%) were the most commonly prescribed OAT, followed by trimethoprim-sulfamethoxazole and amoxicillin-clavulanate. OAT was not associated with treatment failure (adjusted OR 0.66; 95% CI 0.18-2.44) and hospitalization length was shorter in the OAT group (6.2 days versus 10.7 days; P < 0.01). APN recurrence caused by ESBL-PE infection within 2 months was not associated with OAT (adjusted HR 0.56; 95% CI 0.16-2.00). OAT reduced hospital stay without adverse effects on treatment outcome. OAT could be safely applied as a carbapenem-saving option in treatment of APN.

A case of gonococcal meningitis caused by Neisseria gonorrhoeae MLST ST7363 in a healthy young adult.

A 37-year-old healthy man was admitted with fever, skin rash, migratory arthralgia, and headache without preceding urogenital symptoms. Sexual contact history and positive CSF culture for Neisseria gonorrhoeae using BacT/Alert blood culture bottles were diagnostic for gonococcal meningitis. Multilocus sequence typing of this isolate showed sequence type (ST) 7363, the most predominant ST among ceftriaxone-resistant strains. The isolate from this case remained susceptible to ceftriaxone although it was resistant to penicillin, tetracycline, and ciprofloxacin. With the high selective pressure of ceftriaxone for treatment of plasmid-mediated ß-lactamase producing N. gonorrhoeae, resistance to ceftriaxone and molecular characteristics should be monitored.

Antifungal prophylaxis with posaconazole tablet and oral suspension in patients with haematologic malignancy: Therapeutic drug monitoring, efficacy and risk factors for the suboptimal level.

BACKGROUND: Posaconazole is used to prevent invasive fungal infections (IFIs) in patients with haematologic malignancy. In this study, we compared plasma posaconazole concentrations (PPCs) and the incidence of breakthrough IFIs between patients with haematologic malignancy receiving posaconazole oral suspension vs tablet. METHODS: We retrospectively collected data on adult patients with haematologic malignancies who received posaconazole prophylaxis during chemotherapy from April 2014 through May 2018. A total of 242 cases with PPCs, 88 in the oral suspension group and 154 in the tablet group, were included in this study. RESULTS: Patients receiving tablets achieved a significantly higher mean PPC than did those on oral suspension (1.631 ± 0.878 µg/mL in the tablet group vs. 0.879 ± 0.585 µg/mL in the oral suspension group). One hundred and thirty-seven of 154 patients (89.0%) receiving tablets had PPCs of 0.7 µg/mL or more, while only 41 of 88 patients (46.6%) receiving oral suspension attained an optimal level (P < .001). The incidence of breakthrough IFIs was significantly higher in the oral suspension group compared with in the tablet group (14.8% of oral suspension vs. 4.5% of tablet; P = .005). In the analysis including patients receiving posaconazole tablets, hypoalbuminemia (< 3.5 g/dL) was found to be a risk factor associated with suboptimal levels (odds ratio: 8.872; 95% confidence interval: 3.011 - 26.141; P < .001). CONCLUSIONS: Suboptimal PPCs in the tablet group were less common than those in the oral suspension group. Therapeutic drug monitoring may be still necessary even in patients receiving posaconazole tablets, especially in those with hypoalbuminemia.