Determining and Comparing the Real-World Effectiveness of Molnupiravir and Nirmatrelvir-Ritonavir in Patients Hospitalized With COVID-19.

BACKGROUND: Current guidelines recommend using nirmatrelvir-ritonavir for coronavirus disease 2019 (COVID-19) treatment, but its potential drug interactions and contraindications limit its applicability in certain categories of patients. The aim of the study was to evaluate the real-world effectiveness of molnupiravir and nirmatrelvir-ritonavir in managing COVID-19 among hospitalized patients. METHODS: We conducted a retrospective cohort study among hospitalized COVID-19 patients who received molnupiravir or nirmatrelvir-ritonavir and did not require baseline supplemental oxygen from February 2022 to January 2023. We compared the effectiveness of molnupiravir and nirmatrelvir-ritonavir with a focus on disease progression. RESULTS: The study included 401 high-risk, hospitalized adult COVID-19 patients who received molnupiravir or nirmatrelvir-ritonavir. No significant difference was found in disease progression, the composite outcome of disease progression (4.0% vs. 1.4%, P = 0.782), and O2 supplementation via nasal prong (21.8% vs. 14.8%, P = 0.115) between the patients treated with molnupiravir and those treated with nirmatrelvir-ritonavir. This finding was similar after 1:1 propensity-score matching. In the multivariate analysis, molnupiravir treatment was not significantly associated with progression to severe disease. CONCLUSION: In conclusion, our findings suggest that similar to nirmatrelvir-ritonavir, molnupiravir has a distinct potential role in COVID-19 treatment, transcending its current perceived status as only a secondary option.

Effectiveness of regdanvimab treatment for SARS-CoV-2 delta variant, which exhibited decreased in vitro activity: a nationwide real-world multicenter cohort study.

Background: Immune-evading severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are emerging continuously. The clinical effectiveness of monoclonal antibody agents that exhibit decreased in vitro activity against SARS-CoV-2 variants needs to be elucidated. Methods: A nationwide, multicenter, retrospective cohort study was designed to evaluate the effectiveness of regdanvimab, an anti-SARS-CoV-2 monoclonal antibody agent. Regdanvimab was prescribed in South Korea before and after the emergence of the delta variant, against which the in vitro activity of regdanvimab was decreased but present. Mild to moderate coronavirus 2019 (COVID-19) patients with risk factors for disease progression who were admitted within seven days of symptom onset were screened in four designated hospitals between December 2020 and September 2021. The primary outcomes, O2 requirements and progression to severe disease within 21 days of admission, were compared between the regdanvimab and supportive care groups, with a subgroup analysis of delta variant-confirmed patients. Results: A total of 2,214 mild to moderate COVID-19 patients were included, of whom 1,095 (49.5%) received regdanvimab treatment. In the analysis of the total cohort, significantly fewer patients in the regdanvimab group than the supportive care group required O2 support (18.4% vs. 27.1%, P < 0.001) and progressed to severe disease (4.0% vs. 8.0%, P < 0.001). In the multivariable analysis, regdanvimab was significantly associated with a decreased risk for O2 support (HR 0.677, 95% CI 0.561-0.816) and progression to severe disease (HR 0.489, 95% CI 0.337-0.709). Among the 939 delta-confirmed patients, O2 support (21.5% vs. 23.5%, P = 0.526) and progression to severe disease (4.2% vs. 7.3%, P = 0.055) did not differ significantly between the regdanvimab and supportive care groups. In the multivariable analyses, regdanvimab treatment was not significantly associated with a decreased risk for O2 support (HR 0.963, 95% CI 0.697-1.329) or progression to severe disease (HR 0.665, 95% CI 0.349-1.268) in delta-confirmed group. Conclusions: Regdanvimab treatment effectively reduced progression to severe disease in the overall study population, but did not show significant effectiveness in the delta-confirmed patients. The effectiveness of dose increment of monoclonal antibody agents should be evaluated for variant strains exhibiting reduced susceptibility.

Regdanvimab for patients with mild-to-moderate COVID-19: a retrospective cohort study and subgroup analysis of patients with the Delta variant.

OBJECTIVES: To evaluate the efficacy and safety of regdanvimab, a neutralizing antibody, in patients with mild-to-moderate SARS-CoV-2 including against the Delta variant. METHODS: A single-center, retrospective, observational cohort study in adults with confirmed COVID-19. The primary end point was the proportion of patients deteriorating with peripheral oxygen saturation <90% in room air, requiring supplemental oxygen therapy above high flow, or experiencing mortality due to COVID-19 up to day 28. RESULTS: A total of 722 patients were eligible; 418 received regdanvimab and 304 received standard of care (SoC), of whom 71.1% (297/418, regdanvimab) and 37.8% (115/304, SoC) were infected with the Delta variant. The proportion of patients with a primary end point event was significantly lower with regdanvimab than SoC (3.1% vs 9.9%; difference: -6.8 [95% confidence interval: -10.9, -2.8]; P = 0.0002). A similar trend was observed in the Delta variant subgroup (regdanvimab, 2.7% vs SoC, 7.0%; difference -4.3 [95% confidence interval: -10.8, 0.2]; P = 0.0827). The secondary efficacy end points supported the primary analysis findings in the overall cohort and Delta variant subgroup. No new safety signals were identified. CONCLUSION: Regdanvimab demonstrated clinical efficacy in the overall cohort and may provide a clinical benefit for patients with mild-to-moderate COVID-19 infected with the Delta variant.

Comparison of antimicrobial resistance in patients with obstructive pyelonephritis associated with ureteral stones and uncomplicated pyelonephritis.

This study aimed to investigate the clinical outcomes of causative microorganisms in obstructive pyelonephritis associated with ureteral stones (OPU) and their antibiotic susceptibilities. This retrospective cohort study included female patients diagnosed with community-acquired acute pyelonephritis (APN) at a tertiary-care hospital between 2008 and 2017. A comparison of APN cases associated with the obstruction of the upper urinary tract by ureteral stones and APN cases without complications was performed. Propensity score (PS) matching was used to adjust the heterogeneity within each group. Of the 588 female patients with community-acquired APN, 107 were diagnosed with OPU and 481 with uncomplicated APN. After PS matching, Enterobacteriaceae strains isolated from OPU cases were more resistant to fluoroquinolones (51.9% vs 16.0%, P < .001). Extended-spectrum ß-lactamase was detected in 22.2% and 21.0% of the Enterobacteriaceae strains isolated from OPU and uncomplicated APN cases, respectively (P = 1.000). The treatment failure rate was similar in OPU and uncomplicated APN groups (16.0% vs 21.0%, P = .545). Patients with OPU may be empirically treated with antibiotics in accordance with the treatment protocol for general pyelonephritis. Clinicians should exercise caution in prescribing fluoroquinolones for treating OPU.

Neutralizing antibody responses in vaccinated and unvaccinated individuals infected with Omicron BA.1 variant.

BACKGROUND: The Omicron variant, with numerous mutations in the spike protein, reduces vaccine-induced immunity, leading to breakthrough infections. However, vaccine protection after infection with the Omicron variant is unclear. AIMS AND METHODS: To compare the neutralizing antibody responses between unvaccinated and vaccinated individuals infected with the Omicron variant, we have collected serial plasma samples from five unvaccinated and four vaccinated individuals with Omicron variant infection, including the first Omicron breakthrough infection case in the Republic of Korea. We evaluated neutralization antibody titers against D614G, Delta, and Omicron using live virus neutralizing assay, and calculated the plaque reduction neutralizing test value. RESULTS: In patients with two-dose vaccinations, neutralizing antibodies against Omicron variant were detected in plasma collected 4-9 days post symptom onset. However, in the plasma from unvaccinated patients and those vaccinated with one dose, neutralizing antibodies against the Omicron variant at the same time point were undetectable. Next, the 1- or 2-dose vaccinated infected groups showed potent cross-neutralizing activity against D614G and Delta variants after 11-14 days. In contrast, the neutralizing antibody titers in the unvaccinated group were low or undetectable. CONCLUSIONS: The major limitation of this study is the small sample size due to the limited samples targeting the first reported cases of Omicron BA.1 variant infection in the Republic of Korea (n = 9). Nevertheless, we found that vaccinated individuals rapidly produced neutralizing antibodies against Omicron, and potent cross-neutralizing antibodies against D614G and Delta upon infection with Omicron.

The First Case of Monkeypox in the Republic of Korea.

A rapid outbreak of monkeypox is ongoing in non-endemic countries since May 2022. We report the first case of monkeypox in the Republic of Korea. This occurred in a 34-year-old male patient who traveled to Europe in June 2022. On the day of his return to the Republic of Korea (June 21, 2022), the patient presented with a genital lesion. The results of the monkeypox real-time polymerase chain reaction tests were positive in the penile ulcer, oropharyngeal and nasopharyngeal specimens. The patient subsequently developed fever and skin rash after hospital admission. Careful history taking along physical examination should be conducted in the patients who have epidemiologic risk factors for monkeypox. Moreover, appropriate specimens should be obtained from lesions and tested for the monkeypox virus.

Comparison of Diagnostic Performance and Confidence between Contrast-Enhanced Computed Tomography Scan and Non-Contrast-Enhanced Computed Tomography Plus Abdomen Ultrasound for Hepatic Metastasis in Patients with Breast Cancer.

Background: The purpose of this study was to compare the performance between noncontrast-enhanced computed tomography (NECT) plus abdominal ultrasound (US) (NECT + US) with contrast-enhanced computed tomography (CECT) for the detection of hepatic metastasis in breast cancer patient with postsurgical follow-up. Methods: A total of 1470 patients without already diagnosed hepatic metastasis were included. All patients underwent US and multiphase CECT including the NECT. Independent reviewers analyzed images obtained in four settings, namely, abdominal US, NECT, NECT + US, and CECT and recorded liver metastases using a 5-grade scale of diagnostic confidence. Sensitivity, specificity (diagnostic performance), and area under the receiver operating characteristic curve (AUC, diagnostic confidence) were calculated. Interoperator agreement was calculated using the kappa test. Results: Reference standards revealed no metastases in 1108/1470 patients, and metastasis was detected in 362/1470 patients. Abdominal US (P < 0.01) and NECT (P = 0.01) significantly differed from CECT, but NECT + US did not significantly differ from CECT in terms of sensitivity (P = 0.09), specificity (P = 0.5), and AUC (P = 0.43). After an additional review of abdominal US, readers changed the diagnostic confidence scores of 106 metastatic lesions diagnosed using NECT. Interobserver agreements were good or very good in all four settings. Additional review of abdominal US with NECT allowed a change in the therapeutic plan of 108 patients. Conclusion: Abdominal US + NECT showed better diagnostic performance for the detection of hepatic metastases than did NECT alone; its diagnostic performance and confidence were similar to those of CECT.

Clinical Effectiveness of Regdanvimab Treatment for Mild-to-Moderate COVID-19: A Retrospective Cohort Study.

Background: In a Phase III study, regdanvimab (CT-P59) reduced the risk of hospitalization or death versus placebo in patients with mild-to-moderate coronavirus disease 2019 (COVID-19). Purpose: We performed a retrospective cohort study of patients with COVID-19 to examine the effect of regdanvimab versus standard of care (SoC) on oxygen saturation. Methods: We reviewed patients with mild-to-moderate COVID-19 confirmed by reverse transcription-polymerase chain reaction at a single hospital in the Republic of Korea. The primary efficacy end point was the proportion of patients deteriorating with peripheral capillary oxygen saturation <94% on room air up to day 28. Results: A total of 127 patients were treated for COVID-19 with regdanvimab, 190 with SoC. The proportion of patients deteriorating with peripheral capillary oxygen saturation <94% on room air up to day 28 was 13.4% with regdanvimab and 39.5% with SoC (P < 0.0001); median time (range) until sustained recovery of fever was 2.0 (0.2-14.8) and 4.2 (0.1-17.1) days, respectively. Supplemental oxygen was required by 23.6% of patients with regdanvimab and 52.1% with SoC (P<0.0001) for a mean of 6.3 and 8.7 days, respectively (P = 0.0113); no patients needed mechanical ventilation. Compared with SoC, hospitalization was shorter with regdanvimab (mean = 11.1 vs 13.6 days; 63.8% vs 31.6% discharged within 11 days; both P values < 0.0001). Fewer regdanvimab-treated patients required remdesivir (14.2% vs 43.2%; P < 0.0001). There were no deaths. Two patients had adverse reactions with regdanvimab. Conclusions: This real-world study indicates that regdanvimab can prevent deterioration in patients with mild-to-moderate COVID-19. (Curr Ther Res Clin Exp. 2022; 83:XXX-XXX).

Efficacy and Safety of Regdanvimab (CT-P59): A Phase 2/3 Randomized, Double-Blind, Placebo-Controlled Trial in Outpatients With Mild-to-Moderate Coronavirus Disease 2019.

Background: Regdanvimab (CT-P59) is a monoclonal antibody with neutralizing activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report on part 1 of a 2-part randomized, placebo-controlled, double-blind study for patients with mild-to-moderate coronavirus disease 2019 (COVID-19). Methods: Outpatients with mild-to-moderate COVID-19 received a single dose of regdanvimab 40 mg/kg (n = 100), regdanvimab 80 mg/kg (n = 103), or placebo (n = 104). The primary end points were time to negative conversion of SARS-CoV-2 from nasopharyngeal swab based on quantitative reverse transcription polymerase chain reaction (RT-qPCR) up to day 28 and time to clinical recovery up to day 14. Secondary end points included the proportion of patients requiring hospitalization, oxygen therapy, or mortality due to COVID-19. Results: Median (95% CI) time to negative conversion of RT-qPCR was 12.8 (9.0-12.9) days with regdanvimab 40 mg/kg, 11.9 (8.9-12.9) days with regdanvimab 80 mg/kg, and 12.9 (12.7-13.9) days with placebo. Median (95% CI) time to clinical recovery was 5.3 (4.0-6.8) days with regdanvimab 40 mg/kg, 6.2 (5.5-7.9) days with regdanvimab 80 mg/kg, and 8.8 (6.8-11.6) days with placebo. The proportion (95% CI) of patients requiring hospitalization or oxygen therapy was lower with regdanvimab 40 mg/kg (4.0% [1.6%-9.8%]) and regdanvimab 80 mg/kg (4.9% [2.1%-10.9%]) vs placebo (8.7% [4.6%-15.6%]). No serious treatment-emergent adverse events or deaths occurred. Conclusions: Regdanvimab showed a trend toward a minor decrease in time to negative conversion of RT-qPCR results compared with placebo and reduced the need for hospitalization and oxygen therapy in patients with mild-to-moderate COVID-19. Clinical trial registration : NCT04602000 and EudraCT 2020-003369-20.

A critical review of abdominopelvic computed tomography for the detection of asymptomatic metastasis in new and recurrent breast cancers.

AIM: Abdominopelvic computed tomography (APCT) is a commonly used staging investigation to detect asymptomatic metastasis in breast cancer including early breast cancer (EBC). This study aimed to assess the usefulness of APCT in breast cancers at each clinical stage. METHODS: Patients with new or recurrent invasive breast cancer between January 2009 and December 2014 were included in the study. All staging APCT results were reviewed to evaluate its yield and false positive rate (FPR) and how many investigations are needed to confirm indeterminate results. Odds ratios (ORs) for positive APCT results were calculated for possible risk factors for asymptomatic metastasis. RESULTS: Sixty-five asymptomatic metastases were detected from 1002 APCTs, giving an overall yield of 6.5%. The overall false-positive rate was 14.9 % due to 149 indeterminate findings that were found not to be metastases after further investigations or observation. Whereas the APCTs have a low yield of 3.1% in EBC, but advanced breast cancer and recurrent breast cancer have a high incidence of asymptomatic metastases (13.8% and 16.3%, respectively). The most common cause of indeterminate findings was small liver nodules, including liver cysts and liver hemangiomas. Human epidermal growth factor receptor2 (HER2) status and tumor stage are most significant predictors for positive results of staging APCT scans with high ORs (3.9 and 3.7, respectively). CONCLUSION: Staging APCT is associated with a high incidence of FPRs and low yield, especially among EBCs. It is desirable to choose this investigation more selectively according to HER2 status and tumor stage.

Safety, Virologic Efficacy, and Pharmacokinetics of CT-P59, a Neutralizing Monoclonal Antibody Against SARS-CoV-2 Spike Receptor-Binding Protein: Two Randomized, Placebo-Controlled, Phase I Studies in Healthy Individuals and Patients With Mild SARS-CoV-2 Infection.

PURPOSE: Neutralizing antibodies can reduce SARS-CoV-2 cellular entry, viral titers, and pathologic damage. CT-P59 (regdanvimab), a SARS-CoV-2 neutralizing monoclonal antibody, was examined in 2 randomized, double-blind, placebo-controlled, single ascending dose, Phase I studies. METHODS: In study 1.1, healthy adults were sequentially enrolled to receive CT-P59 10, 20, 40, or 80 mg/kg or placebo. In study 1.2, adult patients with mild SARS-CoV-2 infection were enrolled to receive CT-P59 20, 40, or 80 mg/kg or placebo. Primary objectives of both studies were safety and tolerability up to day 14 after infusion. Secondary end points included pharmacokinetic properties. Study 1.2 also measured virology and clinical efficacy. FINDINGS: Thirty-two individuals were randomized to study 1.1 (6 per CT-P59 dose cohort and 8 in the placebo cohort). By day 14 after infusion, adverse events (AEs) were reported in 2 individuals receiving CT-P59 20 mg/kg (headache and elevated C-reactive protein levels) and 1 receiving CT-P59 40 mg/kg (pyrexia) (all Common Terminology Criteria for Adverse Events grade 1). In study 1.2, 18 patients were randomized (5 per dose cohort and 3 in the placebo cohort). Sixteen AEs were reported in 10 patients receiving CT-P59. No AEs in either study led to study discontinuation. Greater reductions in viral titers were reported with CT-P59 than placebo in those with maximum titers >105 copies/mL. Mean time to recovery was 3.39 versus 5.25 days. IMPLICATIONS: CT-P59 exhibited a promising safety profile in healthy individuals and patients with mild SARS-CoV-2 infection, with potential antiviral and clinical efficacy in patients with mild SARS-CoV-2 infection. ClinicalTrials.gov identifier: NCT04525079 (study 1.1) and NCT04593641 (study 1.2).

Protection and Response of a Tertiary Hospital in South Korea to the COVID-19 Outbreak.

OBJECTIVE: Here, we present an overview of how a tertiary hospital responded to maintain necessary activities and protect patients and staff from the coronavirus disease (COVID-19) outbreak. METHODS: Gil Medical Center, a tertiary hospital in Incheon, has operated a special response team since January 21, 2020. All visitors were assessed for body temperature and respiratory symptoms, and screened for recent overseas travel. Suspected COVID-19 patients were taken to a screening clinic. All febrile patients with or without respiratory symptoms were taken to a respiratory safety clinic. An isolation ward, which consisted of 10 negative-pressure rooms, was used to treat confirmed cases. More than 120 beds were prepared for the outbreak, and patients with pneumonia were preemptively isolated. RESULTS: By May 5, 480 960 visitors were assessed at the control station, 3350 patients visited the triage center, and 1794 were treated in the respiratory safety clinic. Seventeen confirmed cases were admitted to the negative isolation ward, and 350 patients with pneumonia were preemptively isolated. A total of 2977 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction tests were performed. CONCLUSIONS: While tertiary hospitals play an important role in treating both COVID-19 patients and non-COVID-19 patients, hospital staff have to protect themselves from unexpected in-hospital transmission. A multifaceted response must be undertaken to protect tertiary hospitals and their staff during the COVID-19 epidemic.

Clinical and computed tomography factors associated with sepsis in women with clinically uncomplicated pyelonephritis.

OBJECTIVE: Sepsis is major determinants of prognosis in acute pyelonephritis (APN). This study aimed to assess factors associated with the development of sepsis among patients with clinically uncomplicated APN. SUBJECTS AND METHODS: We examined 463 patients presenting to our hospital without complications. We assessed clinical factors including demographic and laboratory features. Renal and extrarenal features on computed tomography (CT) were also analyzed. Risk factors of sepsis are assessed. RESULTS: The study included 361 patients without (78.0%) and 102 patients with sepsis (22.0%). Crude and attributable mortality rates were 3.9% and 2.0% versus 1.4% and 0.6%, respectively, among patients with and without sepsis. Clinical risk factors for sepsis were age >65 years (odds ratio [OR] 1.79, P = 0.02), absence of flank pain (OR 1.59, P = 0.04), absence of costovertebral tenderness (OR 1.89, P = 0.03), diabetes mellitus (OR 2.25, P = 0.02), bacteremia (OR 2.8, P = 0.01), C-reactive protein level >100 mg/L (OR 1.42, P = 0.02), and lack of previous APN history (OR 1.76, P = 0.04). APN grade IV (OR 3.16, P = 0.01), high grade hydronephrosis (OR 1.50, P = 0.03), diffuse peritoneal thickening (OR 4.12, P = 0.01), and acute interstitial pulmonary edema (OR 3.73, P = 0.01) were the CT features predictive of septic shock. CONCLUSIONS: Although uncomplicated APN was largely non-fatal, several clinical and CT features could lead to sepsis. Our findings may be useful for predicting sepsis risk and deciding whether intravenous antibiotic treatment and intensive management should be initiated for uncomplicated APN.

Diagnostic accuracy of non-contrast abdominopelvic computed tomography scans in follow-up of breast cancer patients.

OBJECTIVES: To evaluate the effectiveness of follow-up with non-enhanced CT (NECT) in patients with breast cancer. METHODS: The present retrospective study included 1396 patients with breast cancer. Group A included patients with no metastasis to evaluate the diagnostic performance of NECT in detecting newly developed metastasis. Group B included patients with known hepatic metastasis to evaluate the accuracy of NECT for the assessment of hepatic metastasis. RESULTS: Group A included 895 patients (mean age 52.8 years). Among them, 145 patients had 160 metastases. The per-patient sensitivities for diagnosing newly developed metastasis were 68.3 and 53.8% according to the two reviewers, while the per-lesion sensitivities were 89.4 and 85.0%. Sensitivities for bone metastasis were 98.9 and 95.9%, while sensitivities for hepatic metastasis were 73.7 and 68.4%. In group B, the accuracy of hepatic metastasis response evaluation according to the RECIST criteria was 70.8% for reviewer 1 and 63.8% for reviewer 2. CONCLUSIONS: NECT showed inadequate diagnostic performance in detecting newly developed metastasis and in evaluating the response of hepatic metastasis. However, NECT can be utilized as a follow-up modality in patients with decreased renal function or hypersensitivity to iodinated contrast media. ADVANCES IN KNOWLEDGE: The risk of side effects of contrast media should be considered as important when NECT can be utilized as a follow-up modality in decreased renal function patients.

Acute cholecystitis: predictive clinico-radiological assessment for conversion of laparoscopic cholecystectomy.

BACKGROUND: Previous studies evaluating predictive factors for the conversion from laparoscopic to open cholecystectomy have reported conflicting conclusions. PURPOSE: To create a risk assessment model to predict the conversion from laparoscopic to open cholecystectomy in patients with acute calculous cholecystitis. MATERIAL AND METHODS: A retrospective review of patients with acute calculous cholecystitis with available preoperative contrast-enhanced computed tomography (CT) findings who underwent laparoscopic cholecystectomy was performed. Forty-four parameters-including demographics, clinical history, laboratory data, and CT findings-were analyzed. RESULTS: Among the included 581 patients, conversion occurred in 113 (19%) cases. Multivariate analysis identified obesity (odd ratio [OR] 2.58, P = 0.04), history of abdominal surgery (OR 1.78, P = 0.03), and prolonged prothrombin time (OR 1.98, P = 0.03) as predictors of conversion. In preoperative CT findings, the absence of gallbladder wall enhancement (OR 3.15, P = 0.03), presence of a gallstone in the gallbladder infundibulum (OR 2.11, P = 0.04), and inflammation of the hepatic pedicle (OR 1.71, P = 0.04) were associated with conversion. Inter-observer agreement for CT study interpretation was very good (range 0.81-1.00). A model was created to calculate the risk for conversion, with an area under the receiver operating characteristic curve of 0.87. The risk for conversion, estimated based on the number of factors identified, was in the range of 5.3% (with one factor) to 86.4% (with six factors). CONCLUSION: Obesity, history of abdominal surgery, prolonged prothrombin time, absence of gallbladder wall enhancement, presence of a gallstone in the gallbladder infundibulum, and inflammation of the hepatic pedicle are associated with conversion of laparoscopic to open cholecystectomy.

A retrospective study of pyogenic liver abscess caused primarily by Klebsiella pneumoniae vs. non-Klebsiella pneumoniae: CT and clinical differentiation.

PURPOSE: The incidence of Klebsiella pneumoniae pyogenic liver abscesses (KP-PLA) is increasing. However, its diagnosis and treatment are often delayed, leading to complications. In this study, we aimed to retrospectively compare computed tomographic (CT) features of KP-PLAs with those of abscesses caused by other bacterial pathogens (non-KP-PLAS) and to further identify prognostic factors for PLA. METHODS: Data of 219 study patients including clinical presentation, comorbid conditions, metastatic infection, treatment duration, and mortality were retrospectively collated. CT characteristics of abscesses were recorded. Etiology was established by pus and/or blood culture. The differentiating CT features and clinical findings were compared between the monomicrobial KP-PLA and non-KP-PLA groups. Furthermore, factors related to in-hospital case fatality were analyzed. RESULTS: Multivariate analysis identified thin-walled abscesses, absent rim enhancement, metastatic infection, and absence of underlying biliary tract disease as significant predictors of KP-PLA. With 3/4 criteria applied in combination, a specificity of 96.5% was achieved for KP-PLA diagnosis. The in-hospital mortality rate was 3.7%. Multivariate analysis revealed that diabetes mellitus (P = 0.031), multiple abscesses (P = 0.026), internal gas bubble (P = 0.041), metastatic infection (P = 0.004), and septic shock (P = 0.002) were significantly associated with mortality. CONCLUSION: Thin-walled abscess, metastatic infection, absence of rim enhancement, and absence of underlying biliary tract disease are potentially useful CT findings for early KP-PLA diagnosis.

Prolonged fever is not a reason to change antibiotics among patients with uncomplicated community-acquired acute pyelonephritis.

The study aimed to determine the pattern of fever resolution among febrile patients undergoing treatment for acute pyelonephritis (APN) and prove that switching therapy based solely on persistent fever beyond 72 hours of antibiotics treatment may be unwarranted.For the purpose of this study, non-responders were defined as those patients who had a persistent fever over 72 hours after the initiation of antibiotic therapy. Responders were defined as those patients who became afebrile in less than 72 hours after the initiation of antibiotic therapy. Clinical cure was defined as the complete resolution of all symptoms during antibiotic therapy without recurrence during the follow-up period.A total of 843 female patients with uncomplicated community-acquired APN met all inclusion criteria. The non-responder group comprised of 248 patients (29%), and the remaining patients constituted the responder group. The median initial C-reactive protein level was higher (15.6 mg/dl vs 12.6 md/dl, P < .001) and bacteremia was more frequent (31% vs 40%, P = .001) in the non-responder group. Escherichia coli (E. coli) was the most common pathogen in both groups; there was no significant difference between the groups in the etiology of APN. Antimicrobial resistance and extended spectrum ß-lactamase producing strains had an increasing trend in the non-responder group but there was no significant difference between the groups.This study shows that it is difficult to identify patients at risk of uncomplicated community-acquired APN by antibiotic-resistant pathogens based exclusively on persistent fever. Patients with a prolonged fever for more than 72 hours show similar antibiotic susceptibility patterns and are not associated with adverse treatment outcomes. Therefore, switching of current antibiotics to broad-spectrum antibiotics should be reserved in this patient population until antibiotic susceptibility test results are available.

Sternoclavicular septic arthritis caused by Staphylococcus aureus: excellent results from medical treatment and limited surgery.

Background: Aggressive surgery such as en bloc joint resection is favored for treating uncommon sternoclavicular (SC) septic arthritis, based on expert opinion and small case series. We analyzed the clinical characteristics and treatment outcomes of patients with Staphylococcus aureus SC septic arthritis treated medically or with limited surgery. Methods: All adult patients with this septic arthritis at the Asan Medical Center between September 2009 and December 2016 were reviewed. Limited surgery was defined as simple incision, drainage, and debridement of the infected joint. Results: Of 22 patients enrolled, 11 received medical treatment only, and 11 underwent limited surgery, and none underwent aggressive surgery. Most patients (73%) had underlying predisposing conditions such as infection at a distant site, diabetes and liver cirrhosis, and none had intravenous drug abuse or HIV infection. Complications such as chest wall and/or neck abscess, clavicular and/or sternal osteomyelitis were identified in 18 patients (82%). Patients with chest wall and/or neck abscesses tended more often to undergo limited surgery than patients without such abscesses (73% vs. 27%, p = .09). The median duration of intravenous antibiotics was 35 days (IQR, 25-46 days). Treatment was successful in all cases. In a median 53-week follow-up (IQR, 8-171 weeks), there was no relapse of arthritis or joint deterioration. Conclusions: Medical treatment alone or with limited surgery could be successful therapeutic strategies for complicated S. aureus SC septic arthritis in selected patients.

Molecular detection of Coxiella burnetii in heart valve tissue from patients with culture-negative infective endocarditis.

Coxiella burnetii is a common cause of blood culture-negative infective endocarditis (IE). Molecular detection of C burnetii DNA in clinical specimens is a promising method of diagnosing Q fever endocarditis. Here, we examined the diagnostic utility of Q fever polymerase chain reaction (PCR) of formalin-fixed heart valve tissue from patients with blood culture-negative IE who underwent heart valve surgery. Clinical and laboratory data of patients with blood culture-negative IE who underwent heart valve surgery during a 6-year period and for whom biopsy tissues were available were reviewed retrospectively. Blood culture-positive IE patients who underwent heart valve surgery within the last 3 years were used as controls. Heart valve samples were cultured and also subjected to histological examination and PCR for Q fever, brucellosis, and bartonellosis. Data from 20 patients with blood culture-negative IE and 20 with blood culture-positive IE were analyzed. Eight cases of blood culture-negative IE were PCR-positive for C burnetii (40%; 95% confidence interval, 19-64). No specimen was PCR-positive for brucellosis or bartonellosis. Histologically, 4 of 8 specimens with a positive Q fever PCR result were characterized by clusters of multinucleated giant cells without a fibrin ring. None of 20 patients with blood culture-negative IE received anti-Coxiella antibiotic therapy due to lack of clinical suspicion. Six-month mortality was higher in the Q fever PCR-positive group than in the Q fever PCR-negative group [38% (3/8) vs 0% (0/12), P = .049). Of the 20 patients with blood culture-positive IE, none yielded a positive Q fever PCR result for valve tissue. Approximately 40% of patients with culture-negative IE who received heart valve surgery were PCR-positive for Q fever; patients without clinical suspicion suffered high mortality. These data suggest that Q fever IE in patients with culture-negative IE is often missed in routine clinical practice.

Clinical characteristics and outcomes of patients with chronic disseminated candidiasis who need adjuvant corticosteroid therapy.

We performed a retrospective study involving 21 patients with chronic disseminate candidiasis (CDC) and 38 patients with candidemia. Neutropenia of >2 weeks' duration was more common in those with CDC (71%) than in those with candidemia (26%, P < .001), and the azole-resistant rate in patients with CDC (5%) was lower than that in those with candidemia (29%, P = .03). Of the 21 patients with CDC, five (24%) needed adjuvant corticosteroid therapy due to persistent debilitating fever (median, 19 days). Rapid defervescence (median, 5 days) occurred after adjuvant corticosteroid therapy. However, there were no significant differences in 90-day mortality between CDC patients with and without corticosteroid therapy. Further prospective data are needed to define the role of steroids in this setting.