Efficacy of cefoperazone/sulbactam for ESBL-producing Escherichia coli and Klebsiella pneumoniae bacteraemia and the factors associated with poor outcomes.

OBJECTIVE: We aimed to assess the efficacy of cefoperazone/sulbactam (CPZ/SUL) in extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales infections and identify factors influencing outcomes. METHODS: This retrospective multicentre study was conducted in Taiwan (January 2015 to December 2020) and examined the efficacy of CPZ/SUL treatment in ESBL-producing Enterobacterales bacteraemia. The minimum inhibitory concentrations (MICs) were determined using agar dilution; ESBL/AmpC genes were detected using polymerase chain reaction. The primary outcome was clinical success, whereas the secondary outcome was 30-day mortality. Clinical success was defined as the complete resolution of clinical signs and symptoms of K. pneumoniae or E. coli infection, with no evidence of persistent or recurrent bacteraemia. The factors influencing outcomes were identified using a multivariate analysis. RESULTS: CPZ/SUL demonstrated a clinical success rate of 82.7% (91/110) in treating ESBL-producing Enterobacterales bacteraemia, with a 30-day mortality rate of 9.1% (10/110). Among 110 ESBL-producing isolates, a high clinical success rate was observed at an MIC of ≤32/32 mg/L. Multivariate analysis revealed that a Charlson comorbidity index (CCI) of ≥6 was associated with lower clinical success [odds ratio (OR): 5.80, 95% confidence interval (CI): 1.15-29.14, P = 0.033]. High Sequential Organ Failure Assessment scores (≥6) were significantly associated with increased 30-day mortality (OR: 14.34, 95% CI: 1.45-141.82, P = 0.023). DISCUSSION: CPZ/SUL demonstrated a clinical success rate of 82.7% (91/110) in treating ESBL-producing Enterobacterales bacteraemia. Treatment success was evident when the CPZ and SUL MIC was ≤32/32 mg/L. Comorbidities (CCI ≥6) were associated with lower clinical success, while disease severity (Sequential Organ Failure Assessment score ≥6) correlated with higher mortality.

Multicenter study on clinical outcomes and poor prognostic factors in patients with Klebsiella pneumoniae bacteremia receiving cefoperazone/sulbactam treatment.

BACKGROUND: Infections caused by Klebsiella pneumoniae are common and result in high mortality rates. In vitro studies demonstrated the potency of cefoperazone/sulbactam (CPZ/SUL) against Klebsiella pneumoniae. However, the clinical efficacy of CPZ/SUL for the treatment of K. pneumoniae bacteremia has not been studied. OBJECTIVES: This study aimed to associate the clinical outcomes of patients with bacteremia with the minimal inhibitory concentrations (MICs) of CPZ/SUL against the causative K. pneumoniae isolates. METHODS: This multicenter, retrospective study was conducted in Taiwan between July 2017 and April 2021. Patients with K. pneumoniae bacteremia treated with CPZ/SUL were enrolled in this study. CPZ/SUL MICs were determined using the agar dilution method. Data on the patients' clinical outcomes and characteristics were collected and analyzed. RESULTS: In total, 201 patients were enrolled. Among the causative K. pneumoniae isolates, 180 (89.5%) were susceptible to CPZ/SUL. Most patients (n = 156, 77.6%) had favorable outcomes. The 30-day mortality rate was 11.9% (n = 24). Multivariate risk analyses showed that higher APACHE II score (Odds Ratio [OR], 1.14; Confidence Interval [CI], 1.07-1.21; p < 0.001), metastatic tumors (OR, 5.76; CI, 2.31-14.40; p < 0.001), and causative K. pneumoniae CPZ/SUL MICs > 16 µg/ml (OR, 4.30; CI, 1.50-12.27; p = 0.006) were independently associated with unfavorable outcomes. CONCLUSION: Patients with K. pneumoniae bacteremia treated with CPZ/SUL at a ratio 1:1 had favorable outcomes when the CPZ/SUL MICs were ≤ 16 µg/ml. Patients with higher APACHE II scores and metastatic tumors had unfavorable outcomes.

Successful treatment of 28 patients with coronavirus disease 2019 at a medical center in Taiwan.

BACKGROUND: Coronavirus disease-2019 (COVID-19) is a worldwide pandemic. We present the clinical characteristics and outcomes of 28 COVID-19 patients treated in our hospital in Taiwan. METHODS: Patients with COVID-19, confirmed by positive real-time reverse-transcriptase polymerase chain reaction results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral nucleic acids from oropharyngeal swab specimens between February 4, 2020 and July 6, 2020, were enrolled. Their clinical characteristics and outcomes were reviewed. RESULTS: Seventeen of the 28 patients (60.7%) had pneumonia. The most frequent symptoms were cough (n = 23, 82.1%) and fever (n = 17, 60.7%). The development of pneumonia was associated with age ≥40 years (p < 0.024), body mass index (BMI) ≥25 kg/m2 (p = 0.014), fever (p = 0.007), shortness of breath (p = 0.036), chills ((p = 0.047), and lower platelet counts (<200,000/µL) (p = 0.007). Increased quarantine duration was associated with age ≥40 years (p = 0.026), Charlson index ≥1 (p = 0.037), lower lymphocyte (<1500/uL; p = 0.028) or platelet counts (<200,000/µL) (p = 0.016), lower serum sodium (<140 mEq/L; p = 0.006), and higher C-reactive protein (CRP) level (≥1 mg/dl; p = 0.04). Treatment with hydroxychloroquine or in combination with other medicines did not reduce the quarantine duration. All 28 patients recovered with a median quarantine duration of 27.2 days. CONCLUSION: COVID-19 patients with older age, higher BMI, fever, chills or shortness of breath, lower serum sodium level, lower platelet or lymphocyte count, and higher CRP level may be associated with developing pneumonia or longer quarantine duration.

Multiple sclerosis presenting initially with a worsening of migraine symptoms.

Multiple sclerosis (MS) is a chronic autoimmune disease that targets myelinated axons in the central nervous system. Headache has been reported as a subtle symptom of the onset of MS, with a variable frequency of 1.6-28.5%; however, it remains unclear whether headache is a true symptom of MS onset. Here, we report the case of a female patient who had a history of migraine without aura and experienced worsening of migraine-headache symptoms as the initial manifestation of MS. Three similar cases were reported previously; however, unlike this case, those cases had no history of migraine without aura. In our case, we excluded factors that could trigger migraine attacks, such as changes in weather, drugs, alcohol, caffeine withdrawal, stress, fatigue, lack of sleep, hormonal therapy, diet, and hunger. The patient had one episode of MS attack with the simultaneous presence of asymptomatic gadolinium-enhancing and non-enhancing lesions, including hyperintense lesions in the bilateral periventricular white matter, body of the corpus callosum, and periaqueductal grey matter, as observed on the T2-weighted images obtained at the first brain magnetic resonance imaging. In addition, after the injection of gadolinium contrast, ring enhancement over these lesions was noted in T1-weighted images, which was suggestive of active demyelination. MS was diagnosed according to the McDonald criteria (2010 revision). We conclude that MS with periaqueductal grey matter involvement may present with worsening migraine. It is important to be cautious if any secondary causes exist, especially when the patient has a history of migraine without aura. MS should be one of the differential diagnoses in young women showing a change in headache pattern or poor clinical drug response to migraine treatment accompanied by episodes of focal neurological deficit. Failure to recognize MS may lead to inappropriate treatment and worse prognosis; early diagnosis in patients with MS is essential to improve their clinical outcomes and quality of life.

In vitro and in vivo comparison of eravacycline- and tigecycline-based combination therapies for tigecycline-resistant Acinetobacter baumannii.

Several antimicrobial combination therapies are used to treat multiple drug resistant (MDR) and extensively drug resistant (XDR) Acinetobacter baumannii infections. A novel antibiotic, eravacycline, shows a higher potency than tigecycline. The efficacies of eravacycline-based therapies have not yet been evaluated. We demonstrated the effectiveness of eravacycline- and tigecycline-based combination therapies in XDR and especially tigecycline resistant A. baumannii. Thirteen eligible isolates were selected from 642 non-duplicate Acinetobacter blood isolates from four medical centres in 2010-2014. Tigecycline/imipenem and eravacycline/imipenem combinations were simultaneously effective against some isolates in vitro with fractional inhibitory concentration index of 0.5. In contrast, eravacycline- and tigecycline-based combination therapies provided no additional benefits in mouse survival compared to those for monotherapy. In summary, colistin is still the final resort for XDR-A. baumannii treatment according to the sensitivities. Owning to rapid development of resistance in A. baumannii, novel antibiotics are urgently needed.

Clinical characteristics analysis of COVID-19 patients from the first significant community outbreak by SARS-CoV-2 variant B.1.1.7 in Taiwan as experienced from a single northern medical center.

BACKGROUND/PURPOSE: Clinical characteristics of patients in the first community outbreak of coronavirus disease 2019 (COVID-19) by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant B.1.1.7 in Taiwan have not been characterized. METHODS: SARS-CoV-2 positive specimens from inpatients between May 7 and June 15 in 2021were screen for SARS-CoV-2 B.1.1.7 lineage by VirSNiP assay. Clinical characteristics were reviewed and compared with those from Feb 1 to April 30, 2020 and from Jan 1 to March 31, 2022. RESULTS: One hundred forty-one inpatients from May 7 to June 15, 2021 infected with SARS-CoV-2 B.1.1.7 lineage were included. The major presenting symptoms were fever (88.7%) and cough (59.6%). Incidence of relevant complications including pulmonary embolism, simultaneous infections with bacteria, virus, and fungi were 0.7%, 12.8%, 13.5%, and 2.1%, respectively. Old age, high Charlson comorbidity index, short of breath, and initial critical illness were independently associated with 28-day mortality (all p < 0.05). In comparison to COVID-19 inpatients from Feb 1 to April 30, 2020, patients from the outbreak by SARS-CoV-2 B.1.1.7 lineage were older, more severe in disease condition, higher mortality but less obvious initial presenting symptoms. After implementation of nationwide vaccination campaign in the next half year of 2021, COVID-19 inpatients from Jan 1 to March 31 in 2022 indicated less severe diseases than those infected with SARS-CoV-2 B.1.1.7 lineage. CONCLUSION: COVID-19 inpatients by SARS-CoV-2 variant B.1.1.7 with old age, multiple comorbidities, and more severe disease conditions were associated with increased mortality. Vaccination for this vulnerable populations may be helpful.

Hospital-acquired infections in patients hospitalized with COVID-19: First report from Taiwan.

BACKGROUND: Coronavirus disease 2019 (COVID-19) inpatients may acquire infections from other pathogens during hospital admission. This is the first research on this subject to be reported from Taiwan. METHODS: Confirmed COVID-19 inpatients were enrolled in this study from January 1, 2020 to July 31, 2021. Various types of pathogens in COVID-19 inpatients, with hospital-acquired infections, were identified and analyzed. The clinical characteristics of COVID-19 patients with and without hospital-acquired infections were reviewed and compared. RESULTS: Of the 204 patients included in the study, 32 (15.7%) patients experienced at least one infectious episode. Of 113 recorded episodes of infection, the predominant type was bacterial (88 of 113 infections, 77.9%); the most frequently isolated bacteria were Acinetobacter spp., followed by Stenotrophomonas maltophilia . With regard to viral infections (19 of 113, 16.8%), the Epstein-Barr virus ranked first place among the identified viruses. Four (3.5%) and 2 (1.8%) of 113 infectious episodes were caused by fungi and atypical pathogens. A multivariate analysis revealed that steroid use was an independent factor in hospital-acquired infections (odds ratio [OR], 6.97; 95% confidence interval [CI], 1.15-42.43; p = 0.035). Patients with hospital-acquired infections were associated with increased 28-day and in-hospital mortality (18.8% vs 5.8% and 31.3% and 5.8%; p = 0.023 and <0.01, respectively), and a longer hospital stay (34 vs 19 days; p < 0.001), compared to those without hospital-acquired infections. CONCLUSION: Our study revealed the unique local epidemiology of hospital-acquired infections among COVID-19 inpatients in Taiwan. These patients were associated with increased mortality and prolonged hospital admissions.

Clinical Characteristics of COVID-19 Patients and Application to an Artificial Intelligence System for Disease Surveillance.

During the coronavirus disease (COVID-19) pandemic, we admitted suspected or confirmed COVID-19 patients to our isolation wards between 2 March 2020 and 4 May 2020, following a well-designed and efficient assessment protocol. We included 217 patients suspected of COVID-19, of which 27 had confirmed COVID-19. The clinical characteristics of these patients were used to train artificial intelligence (AI) models such as support vector machine (SVM), decision tree, random forest, and artificial neural network for diagnosing COVID-19. When analyzing the performance of the models, SVM showed the highest sensitivity (SVM vs. decision tree vs. random forest vs. artificial neural network: 100% vs. 42.86% vs. 28.57% vs. 71.43%), while decision tree and random forest had the highest specificity (SVM vs. decision tree vs. random forest vs. artificial neural network: 88.37% vs. 100% vs. 100% vs. 94.74%) in the diagnosis of COVID-19. With the aid of AI models, physicians may identify COVID-19 patients earlier, even with few baseline data available, and segregate infected patients earlier to avoid hospital cluster infections and to ensure the safety of medical professionals and ordinary patients in the hospital.

Biofilm formation is not an independent risk factor for mortality in patients with Acinetobacter baumannii bacteremia.

In the past decades, due to the high prevalence of the antibiotic-resistant isolates of Acinetobacter baumannii, it has emerged as one of the most troublesome pathogens threatening the global healthcare system. Furthermore, this pathogen has the ability to form biofilms, which is another effective mechanism by which it survives in the presence of antibiotics. However, the clinical impact of biofilm-forming A. baumannii isolates on patients with bacteremia is largely unknown. This retrospective study was conducted at five medical centers in Taiwan over a 9-year period. A total of 252 and 459 patients with bacteremia caused by biofilm- and non-biofilm-forming isolates of A. baumannii, respectively, were enrolled. The clinical demographics, antimicrobial susceptibility, biofilm-forming ability, and patient clinical outcomes were analyzed. The biofilm-forming ability of the isolates was assessed using a microtiter plate assay. Multivariate analysis revealed the higher APACHE II score, shock status, lack of appropriate antimicrobial therapy, and carbapenem resistance of the infected strain were independent risk factors of 28-day mortality in the patients with A. baumannii bacteremia. However, there was no significant difference between the 28-day survival and non-survival groups, in terms of the biofilm forming ability. Compared to the patients infected with non-biofilm-forming isolates, those infected with biofilm-forming isolates had a lower in-hospital mortality rate. Patients with either congestive heart failure, underlying hematological malignancy, or chemotherapy recipients were more likely to become infected with the biofilm-forming isolates. Multivariate analysis showed congestive heart failure was an independent risk factor of infection with biofilm-forming isolates, while those with arterial lines tended to be infected with non-biofilm-forming isolates. There were no significant differences in the sources of infection between the biofilm-forming and non-biofilm-forming isolate groups. Carbapenem susceptibility was also similar between these groups. In conclusion, the patients infected with the biofilm-forming isolates of the A. baumannii exhibited different clinical features than those infected with non-biofilm-forming isolates. The biofilm-forming ability of A. baumannii may also influence the antibiotic susceptibility of its isolates. However, it was not an independent risk factor for a 28-day mortality in the patients with bacteremia.

Correlation Between Cefoperazone/Sulbactam MIC Values and Clinical Outcomes of Escherichia coli Bacteremia.

INTRODUCTION: The clinical efficiency of cefoperazone/sulbactam (CPZ/SUL) against Escherichia coli bacteremia was unknown. This study aimed to explore the relationship between CPZ/SUL MIC values and clinical outcomes in Escherichia coli bacteremia. METHODS: A multicenter, retrospective, observational cohort study was conducted in Taiwan between January 2015 and December 2020. Patients treated with CPZ/SUL for E. coli bacteremia were enrolled in the analysis. The CPZ/SUL MICs were determined by using the agar dilution method. The primary outcome was 30-day mortality. RESULTS: Among 247 isolates, 160 (64.8%) isolates were susceptible, 8 (3.2%) were intermediate, and 79 (32.0%) were resistant to cefoperazone. The activity of cefoperazone against cefoperazone-non-susceptible E. coli (n = 87) was restored upon combination with sulbactam, with susceptibility ranging from 0% to 97.7%. The 30-day mortality was 4.5% (11/247) and overall clinical success rate was 91.9% (227/247). Multivariate Cox proportional-hazards model revealed that heart failure [adjusted relative risk (ARR), 5.49; 95% confidence interval (CI) 1.31-23.02; p = 0.020], malignancy (ARR 7.50; 95% CI 2.02-27.80; p = 0.003), SOFA score (ARR 1.29; 95% CI 1.09-1.52; p = 0.003), and CPZ/SUL MIC ≥ 64 mg/L (ARR 11.31; 95% CI 1.34-95.52; p = 0.026) were independently associated with 30-day mortality. No statistically significant differences in 30-day mortality were found between groups with or without cefoperazone susceptibility (3.4% vs. 5.0%, p = 0.751, respectively). CONCLUSIONS: Patients with E. coli bacteremia who were treated with CPZ/SUL had a favorable outcome when the MICs of the isolates were ≤ 16 mg/L and a high risk of mortality with MICs ≥ 64 mg/L.

A multicenter study on clinical characteristics of Acinetobacter bacteremia in patients with liver cirrhosis.

BACKGROUND: Clinical characteristics and risk factors for mortality of Acinetobacter bacteremia in cirrhotic patients have not been investigated. METHODS: Acinetobacter bacteremia cases from four medical centers were collected from 2009 to 2014, to compare between patients with and without liver cirrhosis. Risk factors for mortality of Acinetobacter bacteremia among cirrhotic patients were identified using multivariate logistic regression. RESULTS: Among the patients with Acinetobacter bacteremia, 72 had liver cirrhosis and 816 had not. Patients with cirrhosis were younger (57.5 [50-71] vs. 72 [50.25-71], p < 0.001), had more solid tumor (51.4% vs. 31.4%, p = 0.001), lower Acute Physiology and Chronic Health Evaluation II (APACHE II) scores (17 [12-24] vs. 20 [13-28], p = 0.012), less sourced from pneumonia (19.4% vs. 35.8%, p = 0.008), and less caused by Acinetobacterbaumannii (33.3% vs. 50.6%, p = 0.007) than those without. After matching for age, sex, and causative pathogens, the 30-day mortality (34.7% vs. 29.2%, p = 0.592) and APACHE II scores (17 vs. 17, p = 0.769) were not significant. APACHE II score (odds ratio [OR], 1.146; 95% confidence interval [CI], 1.035-1.268; p = 0.009), bacteremia caused by A. baumannii (OR, 20.501; 95% CI, 2.301-182.649; p = 0.007), and solid tumor (OR, 18.073; 95% CI, 1.938-168.504; p = 0.011) were independent risk factors for 30-day mortality of cirrhotic patients with Acinetobacter bacteremia. CONCLUSION: Even though cirrhotic patients with Acinetobacter bacteremia were younger and had lower APACHE II scores than non-cirrhotic patients, the mortality rates were insignificantly different between the two groups.

Quantification and comparison of virulence and characteristics of different variants of carbapenemase-producing Klebsiella pneumoniae clinical isolates from Taiwan and the United States.

BACKGROUND/PURPOSE: The emergence of Klebsiella pneumoniae carbapenemase (KPC)-producing strains is a challenge for clinicians. The characteristics and virulence of variants of KPC-producing K. pneumoniae isolates were evaluated. METHODS: Five clinical isolates-three KPC subtypes from Taiwan (KPC2-TW, KPC3-TW, and KPC17-TW) and two clinical strains from the United States (US; KPC2-US, KPC3-US)-were included. Virulent traits and capsular serotypes were analyzed by Polymerase Chain Reaction (PCR). Serum killing, neutrophil phagocytosis, and mice lethargy studies were performed to evaluate virulence. RESULTS: Multilocus sequence typing (MLST) demonstrated that KPC2-TW and KPC17-TW belonged to sequence type (ST)11, and KPC2-US, KPC3-US, and KPC3-TW to ST258. KPC3-TW expressed capsular serotype K1, whereas the others were non-K1/K2/K5 isolates. MLST analysis indicated that ST11 strains were serum resistant, whereas ST258 isolates were serum sensitive. ST11 isolates exhibited significantly higher 15-minute phagocytic rates than ST258 isolates (70.28 ± 16.68% vs. 34.88 ± 10.52%, p < 0.001). The capsular serotype K1 strain was more resistant to neutrophil phagocytosis than non-K1/K2/K5 isolates (27.1 ± 10.23% vs. 54.46 ± 20.94%, p = 0.050). All KPC-producing strain variants from Taiwan and the US demonstrated less virulence in a mouse lethality study, where the LD50 ranged from approximately 10(6) colony-forming units (CFU) to >10(7) CFU. Immunological responses were not significantly correlated with KPC subtype; however, responses were associated with MLST and capsular serotype. CONCLUSION: Production of KPC itself was not associated with increased virulence despite different variants of KPC. The ST11 KPC-producing strain was resistant to serum killing, whereas capsular ss K1 was associated with resistance to neutrophil phagocytosis.

Recreational nitrous oxide abuse-induced vitamin B12 deficiency in a patient presenting with hyperpigmentation of the skin.

Vitamin B12 deficiency causes skin hyperpigmentation, subacute combined degeneration of the spinal cord, and megaloblastic anemia. Although vitamin B12 deficiency rarely occurs in well-nourished, healthy, young people, nitrous oxide (N2O) intoxication is an important cause of vitamin B12 deficiency in this cohort. N2O, a colorless gas used as an anesthetic since the late 19th century because of its euphoric and analgesic qualities, is now used as a recreational drug and is available via the Internet and at clubs. Here, we describe the case of a 29-year-old woman presenting with skin hyperpigmentation as her only initial symptom after N2O abuse for approximately 2 years. N2O intoxication-induced vitamin B12 deficiency was diagnosed based on the skin pigmentation that had manifested over the dorsa of her fingers, toes, and trunk, coupled with myeloneuropathy of the posterior and lateral columns, a low serum vitamin B12 level, an elevated serum homocysteine level, and the N2O exposure revealed while establishing the patient's history. Symptoms improved significantly with vitamin B12 treatment. We recommend that dermatologists consider N2O intoxication-induced vitamin B12 deficiency as a potential cause of skin hyperpigmentation and myeloneuropathy of the posterior and lateral columns in young, otherwise healthy patients. Failure to recognize this presentation may result in inappropriate treatment, thus affecting patients' clinical outcomes.