Pyogenic spondylitis caused by Klebsiella pneumoniae: should the possibility of hypervirulent Klebsiella pneumoniae be considered?

BACKGROUND: Klebsiella pneumoniae is rare but the second most common causative agent among gram-negative bacteria that cause pyogenic spondylitis. However, there are no available studies on the serotype, virulence factors, and clinical characteristics associated with K. pneumoniae-caused pyogenic spondylitis. Accordingly, we investigated the clinical characteristics of pyogenic spondylitis, K1 and K2 serotypes, and virulence factors of K. pneumoniae. METHODS: We reviewed the microbiological reports of specimens collected between January 2014 and December 2019 as well as the medical records of patients with pyogenic spondylitis caused by K. pneumoniae. We also evaluated K1 and K2 serotypes and the virulent genes rmpA, iutA, mrkD, ybtS, entB, and kfu. Strains that possessed rmpA and iutA were defined as hypervirulent K. pneumoniae. RESULTS: Six patients with pyogenic spondylitis caused by K. pneumoniae were enrolled in the study. The capsular serotypes K1 and K2 were present in 66.7% (4/6) of cases, and the hypervirulent strains were present in 88.3% (5/6) of cases. All patients had community-acquired infections, and all strains isolated were susceptible to antimicrobial agents. Intravenous antibiotic treatment continued for 2-7 weeks, and no patient underwent decompressive operation or surgical debridement. There was no recurrence. One patient died from pneumonia with a septic lung. CONCLUSION: Hypervirulent K. pneumoniae is a rare but possible causative agent associated with pyogenic spondylitis.

Invasive Hypervirulent Klebsiella pneumoniae Syndrome Originating from an Anorectal Abscess as Opposed to a Pyogenic Liver Abscess.

An immunocompetent 49-year-old man presented with swelling and pain in the lower region of his left leg that had lasted for 4 weeks. The diagnosis was severe pyomyositis and osteomyelitis in the lower left leg caused by hypervirulent Klebsiella pneumoniae (hvKP) along with multiple metastatic infections in the kidneys, lungs, and brain originating from an anorectal abscess. A virulence-gene analysis revealed that the isolated K. pneumoniae harbored rmpA, entB, ybtS, kfu, iutA, mrkD, and allS-virulence genes and belonged to the K1 capsular serotype. After repeated abscess drainage procedures, intravenous ceftriaxone was administered for more than 10 weeks, and the patient's infection was controlled. We focused on the clinical features of hvKP originating from an anorectal abscess without a pyogenic liver abscess. We suggest that hvKP be considered a causative pathogen of pyomyositis and osteomyelitis resulting in multiple metastatic infections in an immunocompetent patient, and more information on the unexpected multiple metastatic infections should be obtained from a virulence analysis of K. pneumoniae.

Transmission Electron Microscopy Confirmation of Orientia tsutsugamushi in Human Bile.

Scrub typhus, the third most frequently reported infectious disease in South Korea, causes serious public health problems. In 2019, we collected a bile specimen from a patient with scrub typhus through percutaneous transhepatic gallbladder drainage and performed transmission electron microscopy to confirm the ultrastructure of Orientia tsutsugamushi.

Risk of cerebro- and cardiovascular disease in patients with scrub typhus.

We analyzed the National Health Insurance Service-National Sample Cohort (NHIS-NSC) data to evaluate whether scrub typhus infection is associated with increased risk of subsequent cardio- and cerebrovascular disease. Compared with the control group, the scrub typhus group showed a greater incidence rate of cardiovascular disease (14.5 vs. 9.0 cases per 1000 person-years). In contrast, the scrub typhus group showed no difference in incidence rate of cerebrovascular disease (12.0 vs. 13.3 cases per 1000 person-years). Based on the NHIS-NSC data, patients with scrub typhus are at greater risk of developing cardiovascular disease long term compared with that of the general population.

Pharmacokinetic Characteristics and Limited Sampling Strategies for Therapeutic Drug Monitoring of Colistin in Patients With Multidrug-Resistant Gram-Negative Bacterial Infections.

BACKGROUND: Colistin is increasingly used as the last therapeutic option for the treatment of multidrug-resistant, Gram-negative bacterial infections. To ensure safe and efficacious use of colistin, therapeutic drug monitoring (TDM) is needed due to its narrow therapeutic window. This study aimed to evaluate the pharmacokinetic (PK) characteristics of colistin and to guide TDM in colistin-treated patients in Korea. METHODS: In a prospective study, we analyzed PK characteristics in 15 patients who intravenously received colistin methanesulfonate twice per day. Colistin methanesulfonate doses were adjusted based on renal function of the subjects. The appropriate blood sampling points for TDM were evaluated by analyzing the correlations between the PK parameters and the plasma concentrations at each time point. RESULTS: The mean values for the minimum, maximum, and average concentrations (Cmin, Cmax, and Caverage) of colistin at steady state were 2.29, 5.5, and 3.38 mg/L, respectively. The dose-normalized Cmin, Cmax, Caverage, and area under the plasma concentration-time curve from 0 to the last measurable concentration (AUClast) showed negative correlations with the creatinine clearance. The combination of the 0- and 2-hour post-dose plasma concentrations was evaluated as the appropriate sampling point for TDM. Two patients reported nephrotoxic adverse events during colistin administration. CONCLUSIONS: Our study clarifies the PK characteristics of successful colistin treatment using TDM. Further evaluations in a larger patient population are needed to confirm the clinical usefulness of colistin TDM.

Recent Increase of Human Granulocytic Anaplasmosis and Co-Infection with Scrub Typhus or Korean Hemorrhagic Fever with Renal Syndrome in Korea.

We report 17 patients with human granulocytic anaplasmosis between January 2015 and September 2018 at two tertiary university hospitals in Korea. Monthly incidence peaked in May and June. Among these patients, we identified three who were co-infected with scrub typhus, and one patient with hemorrhagic fever with renal syndrome.

Early Therapeutic Drug Monitoring of Posaconazole Oral Suspension in Patients With Hematologic Malignancies.

BACKGROUND: Therapeutic drug monitoring (TDM) of posaconazole is usually performed 1 week after starting the drug because of its long half-life. However, previous studies showed that measuring the posaconazole plasma concentration (PPC) on day 3 is effective for predicting steady-state levels. The purpose of this study was to evaluate the relevance of early TDM (day 3) of posaconazole for achieving an optimal PPC. METHODS: This prospective study was conducted from September 2014 to August 2016. A total of 148 patients with acute myeloid leukemia or myelodysplastic syndromes received a 200 mg posaconazole oral suspension 3 times daily for fungal prophylaxis. During the period from September 2014 to December 2015 (control group), no dose adjustment was performed on day 3. During the period from January 2016 to Aug 2016 (early TDM group), the frequency of posaconazole 200-mg administration was increased to 4 times daily in patients whose PPC on day 3 was <400 ng/mL. The cutoff value for optimal PPC on day 8 was defined as 500 ng/mL. RESULTS: In 21 of 107 patients (20%) in the control group, PPC was <400 ng/mL on day 3. In 15 (71%) of these 21 patients, the PPC was suboptimal on day 8. In the early TDM group, the PPC was <400 ng/mL on day 3 in 4 of 41 patients (10%). After increasing the posaconazole administration frequency in these 4 patients, PPC was suboptimal on day 8 in 1 patient (25%). In both groups, 104 patients had a PPC of ≥500 ng/mL on day 3, but 7% (7/104) of these had a suboptimal level on day 8. CONCLUSIONS: Early TDM on day 3 for posaconazole suspension may help more patients achieve optimal drug levels on day 8, although TDM on day 8 is needed even in patients with optimal levels on day 3.

Effect of an intervention targeting inappropriate continued empirical parenteral vancomycin use: a quasi-experimental study in a region of high MRSA prevalence.

BACKGROUND: Despite vancomycin use is a major risk factor for the emergence of vancomycin resistance, it is frequently inappropriately prescribed, especially as empirical treatment. We evaluated the effect of an antimicrobial stewardship intervention targeting for inappropriate continued empirical vancomycin use. METHODS: This was a quasi-experimental study comparing vancomycin use in a 6-month pre-intervention and 6-month intervention period. If empirical vancomycin was continued for more than 96 h without documentation of beta-lactam-resistant gram-positive microorganisms, it was considered inappropriate continued empirical vancomycin use. The intervention consisted of the monitoring of appropriateness by a pharmacist and direct discussion with the prescribing physicians by infectious disease specialists when empirical vancomycin was continued inappropriately. An interrupted time series analysis was used to compare vancomycin use before and during the intervention. RESULTS: Following implementation of the intervention, overall vancomycin consumption decreased by 14.6%, from 37.6 defined daily doses (DDDs)/1000 patient-days in the pre-intervention period to 32.1 DDDs/1000 patient-days in the intervention period (P <  0.001). The inappropriate consumption of vancomycin also declined from 8.0 DDDs/1000 patient-days to 5.8 DDDs/1000 patient-days (P = 0.009). CONCLUSION: Interventions such as direct communication with prescribing physicians and infectious disease clinicians can help reduce the inappropriate continued use of vancomycin.

ArmA and RmtB Were the Predominant 16S RMTase Genes Responsible for Aminoglycoside-resistant Isolates in Korea.

Pathogenic gram-negatives that produce 16S ribosomal RNA methyltransferases (16S RMTases) have already been distributed all over the world. To investigate the predominance of aminoglycoside resistance associated with 16S RMTases in Korea, we collected a total of 222 amikacin resistant Gram-negative clinical isolates from patient specimens between 1999 and 2015 from three hospital banks across Korea. ArmA and rmtB were the predominant 16S RMTase genes responsible for aminoglycoside-resistant isolates circulating in Korean community settings although only one rmtA-producing isolate was detected in 2006.

Two-Year Hospital-Wide Surveillance of Central Line-Associated Bloodstream Infections in a Korean Hospital.

BACKGROUND: Surveillance and interventions of central line-associated bloodstream infections (CLABSIs) had mainly been targeted in intensive care units (ICUs). Central lines are increasingly used outside ICUs. Therefore, we performed a hospital-wide survey of CLABSIs to evaluate the current status and develop strategies to reduce CLBASI rates. METHODS: All hospitalized patients with central venous catheters (CVCs) were screened for CLABSIs from January 2014 through December 2015 at a 1,328 bed tertiary care teaching hospital in Korea using an electronic data-collecting system. Clinical information including type of CVC was collected. CLABSI rates were calculated using the definitions of the National Health and Safety Network after excluding mucosal barrier injury laboratory-confirmed bloodstream infection (BSI). RESULTS: A total of 154 CLABSIs were identified, of which 72 (46.8%) occurred in general wards and 82 (53.2%) in ICUs (0.81 and 2.71 per 1,000 catheter days), respectively. Non-tunneled CVCs were most common (68.6%) among 70 CLABSI events diagnosed within one week of their maintenance. On the other hand, tunneled CVCs and peripherally inserted central catheters (PICCs) were more common (60.5%) among 114 CLABSI events diagnosed more than a week after maintenance. Whereas the majority (72.2%) of CLABSIs in ICUs were associated with non-tunneled CVCs, tunneled CVCs (38.9%) and PICCs (36.8%) were more common in general wards. CONCLUSION: CLABSIs are less common in general wards than in ICUs, but they are more often associated with long-term indwelling catheters. Therefore, interventions to prevent CLABSIs should be tailored according to the type of ward and type of catheter.

Splenic infarction associated with acute infectious mononucleosis due to Epstein-Barr virus infection.

The purpose of this study was to report a case of a previously healthy 20-year-old woman diagnosed with splenic infarction following infectious mononucleosis (IM) by Epstein-Barr virus (EBV) infection and to perform the first systematic review of the clinical characteristics of splenic infarction associated with IM. A systematic review was conducted using English, French, and Japanese literatures of splenic infarction associated with IM due to EBV infection published between 1961 and 2015 in PubMed Medline. A total of 19 cases were extracted from the collected articles. Left upper quadrant (LUQ) pain was observed in 15 (79%) patients. Splenectomy was performed in five (26%) cases, among which four patients presented with stable vital signs. Splenic rupture was accompanied in two (10%) patients. The median time from the onset of IM symptoms to the diagnosis of splenic infarction was 5 days (range, 1-25 days). Fourteen (74%) of 19 patients experienced improvement through medical treatment, and there were no deaths. Splenic infarction associated with IM due to EBV infection can show a favorable clinical outcome after medical treatment. Clinicians should consider the possibility of splenic infarction when patients with IM experience LUQ pain. J. Med. Virol. 89:332-336, 2017. © 2016 Wiley Periodicals, Inc.

Comparative analysis of F-18 FDG PET/CT images between scrub typhus and systemic lupus erythematosus.

This study evaluated the use of F-18 fluorodeoxyglucose (FDG) PET/CT imaging to differentiate between scrub typhus and systemic lupus erythematosus (SLE) in patients presenting with lymphadenopathy. We carried out a retrospective analysis of 18 scrub typhus patients and seven SLE patients, using various imaging parameters, including lymph node size, spleen and liver lengths, the distance between the two farthest lesions (Dmax), and assessments of glucose metabolism. On FDG PET images, we measured the maximum standardized uptake value (SUVmax) of the lymph nodes, spleen, and liver and the mean standardized uptake value (SUVmean) of the liver and spleen. The Dmax values of scrub typhus patients were significantly longer than those of SLE patients, indicating that lymphadenopathy is more generalized in the patients with scrub typhus. The SUVmax values for the lymph node, spleen, and liver were also higher in patients with scrub typhus, while the SUVmean of the liver and spleen did not differ between the two groups. This study is the first to compare FDG PET/CT images between these two conditions, suggesting the potential of this imaging modality to provide critical diagnostic distinctions.

Community-Acquired Solitary Brain Abscesses Caused by Hypervirulent Klebsiella pneumoniae in a Healthy Adult.

A 42-year-old man was admitted to the emergency room complaining of fever and headache. His cerebrospinal fluid showed a cloudy appearance, and his white blood cell count was elevated at 2460/mm3, with a predominance of neutrophils (81%), and abnormal protein and glucose levels (510.7 mg/dL and 5 mg/dL, respectively). A lobulated lesion with rim enhancement, suggestive of abscess, was detected through magnetic resonance imaging. Klebsiella pneumoniae was detected in nasopharyngeal swab and blood cultures. The capsular serotype of K. pneumoniae was K2 and the sequence type determined by multilocus sequence typing was 23. The hypervirulent phenotype was associated with multiple virulent genes, including rmpA, rmpA2, entB, ybtS, kfu, iucA, iutA, iroB mrkD, allS, peg-344, peg-589, and peg-1631. After six weeks of receiving appropriate antibiotics and exhibiting clinical resolution of the brain abscesses, the patient was discharged. We present the first reported case of a healthy community-dwelling adult with solitary brain abscesses, and no other invasive abscesses, related to hypervirulent K. pneumoniae.

Analysis of virulence profiles in clinical isolates of Klebsiella pneumoniae from renal abscesses: clinical significance of hypervirulent isolates.

Introduction: Klebsiella pneumoniae can cause a wide range of infections. Hypervirulent K. pneumoniae (hvKp), particularly associated with the K1 and K2 capsular types, is an increasingly significant microorganism with the potential to cause invasive infections, including renal abscesses. Despite the rising prevalence of hvKp infections, information on renal abscesses caused by K. pneumoniae is limited, and the clinical significance of hvKp associated with specific virulence genes remains elusive. Methods: This study performed at a 1200-bed tertiary hospital sought to identify the clinical and microbiological characteristics of renal abscesses caused by K. pneumoniae, focusing on various virulence genes, including capsular serotypes and multilocus sequence typing (MLST). Results: Over an 8-year period, 64 patients with suspected renal abscesses were reviewed. Ten patients diagnosed with K. pneumoniae-related renal abscesses were ultimately enrolled in the study. Among the isolates from the 10 patients, capsular serotype K2 was predominant (40.0%), followed by K1 (30.0%). The most common sequence type by MLST was 23 (40.0%). In particular, six patients (60.0%) harbored specific genes indicative of hvKp: iucA, peg-344, rmpA, and rmpA2. Conclusions: Our findings highlight the importance of hvKp as a pathogen in renal abscesses. Although the nature of hvKp is relatively unknown, it is widely recognized as a highly virulent pathogen that can infect relatively healthy individuals of various ages and simultaneously cause infections at multiple anatomical sites. Therefore, when treating patients with K. pneumoniae-related renal abscesses, caution is necessary when considering the characteristics of hvKp, such as potential bacteremia, multi-organ abscess formation, and metastatic spread.

Temporal Dynamics of Serum Perforin and Granzyme during the Acute Phase of SARS-CoV-2 Infection.

BACKGROUND: As many SARS-CoV-2 infections are asymptomatic, it could be useful to be able to determine how much time has passed since infection. We explored the changes in the temporal levels of T cell-related proteins (including perforin and granzymes) in the sera of patients with SARS-CoV-2 infection using a commercially available assay. METHODS: This study enrolled 36 patients infected with SARS-CoV-2 and 20 healthy control participants. Blood samples were collected at three different times based on the number of days since symptom onset (early phase: 1-5 days, mid-phase: 6-10 days, late phase: 11-18 days). We assessed the temporal changes in the serum levels of perforin and granzymes in patients with SARS-CoV-2 infection by comparing the results with those obtained in the healthy control group. RESULTS: We identified a significantly low level of perforin in the early phase of SARS-CoV-2 infection (p < 0.01), which was restored to normal during the mid- and late phases of the infection. However, there was no difference in the temporal change in the level of granzymes in SARS-CoV-2-infected patients compared to the healthy control group. CONCLUSIONS: This finding suggests that SARS-CoV-2 infection paralyzed the perforin expression in the early period immediately after infection. Thus, serum perforin is a potential marker for identifying the acute phase of SARS-CoV-2 infection.

Temporal Dynamics of Serum Perforin and Granzymes in Three Different Clinical Stages of Virus-Induced Severe Fever with Thrombocytopenia Syndrome.

Virus-induced severe fever with thrombocytopenia syndrome (SFTS) induces a cell-mediated immune response that likely contributes to virus control in SFTS patients. To identify the temporal changes of the cell-mediated immune response, we investigated the changes in serum levels of perforin and granzymes at early periods after illness onset in SFTS patients. We analyzed 32 SFTS patients and compared the temporal patterns of serum perforin and granzyme A and B to that of 20 healthy control adults using the Mann-Whitney U test. Compared with healthy controls, the mean level of perforin was significantly reduced by 81% (P < 0.01) during the first week after illness onset, whereas granzyme B significantly increased by 4.6-fold (P = 0.02) in the first week after illness onset and decreased to normal afterward. During the study period, there was no significant difference in serum perforin and granzyme. These findings indicate that perforin and granzyme B in serum can be considered possible serologic markers that reflect the clinical stage of SFTS. Additional study is warranted for tracking circulating perforin and granzyme in different ages and for an extended period after illness onset.

Risk factors and clinical features for pulmonary paragonimiasis-associated pneumothorax.

BACKGROUND: Pulmonary paragonimiasis, a food-borne zoonotic helminthiasis, is a parasitic disease of the lung caused by infection with trematodes species of the genus Paragonimus. Although pneumothorax has been reported as occuring with paragonimiasis, to date no study has been performed concerning the clinical features and predictive risk factors for this condition. METHODS: This retrospective study, which aims to fill this gap, was conducted at Jeonbuk National University Hospital. All patients (aged ≥19 years) were diagnosed with paragonimiasis between May 2011 and December 2021. Medical records were reviewed and information concerning age, sex, vital signs, underlying diseases, clinical signs and symptoms, laboratory findings, radiologic findings, treatment, and clinical outcomes was collected. An odds ratio (OR) for the risk factors associated with pneumothorax was calculated using the binary logistic regression model. RESULTS: Among 179 consecutive patients diagnosed with pulmonary paragonimiasis, the postive rate of pneumothorax was 10.6% (19/179). Pneumothorax occurred mostly in the right lung (78.9%, 15/19), and intrapulmonary parenchymal lesions showed an ipsilateral relationship with pneumothorax (94.7%, 18/19). Fifteen patients (78.9%, 15/19) of pneumothorax associated with pulmonary paragonimiasis are accompanied by pleural effusion. Most of patients with pneumothorax (89.5%, 17/19) underwent chest tube insertion as a first treatment. Three patients (15.8%) showed relapses but in no case was a death recorded. Asthma (odds ratio [OR] 8.10, 95% confidence interval [CI] 1.43-45.91), chest pain (OR 8.15, 95% CI 2.70-24.58), and intrapulmonary lesions (OR 8.94, 95% CI 1.12-71.36) were independent risk factors for pulmonary paragonimiasis-associated pneumothorax. CONCLUSIONS: Our findings suggest that clinicians should keep in mind the possibility of pneumothorax when approached by patients with pulmonary paragonimiasis complaining of chest pain, accompanied by intrapulmonary lesions or with asthma as an underlying disease.

Prostatic Abscess Caused by Klebsiella pneumoniae: A 6-Year Single-Center Study.

Hypervirulent Klebsiella pneumoniae (hvKp) is an important strain that can cause multiple organ infections. Although hvKp infection cases are increasing, there is limited information on the prostatic abscesses caused by K. pneumoniae. Furthermore, the clinical significance of hvKp associated with K1 or K2 capsular types or virulence genes in prostatic abscesses remains unclear. Therefore, we aimed to elucidate the clinical and microbiological characteristics of prostatic abscesses caused by K. pneumoniae in relation to various virulence genes. A retrospective study was performed at a 1200-bed tertiary hospital between January 2014 and December 2019. Patients diagnosed with prostatic abscesses with K. pneumoniae isolated from blood, urine, pus, or tissue cultures were enrolled in this study. Our results demonstrate that 30.3% (10/33) of the prostatic abscesses were caused by K. pneumoniae. All strains isolated from patients with prostatic abscesses due to K. pneumoniae were the K1 capsular type, and eight patients (80.0%) carried rmpA and iutA genes that identified hvKp. These findings suggest that hvKp is an important pathogen in prostatic abscesses. Therefore, when treating patients with K. pneumoniae prostatic abscesses, attention should be paid to the characteristics of hvKp, such as bacteremia, multiorgan abscess formation, and metastatic spread.

New Genotypes and Diversity of Orientia tsutsugamushi DNA samples from Patients with Scrub Typhus in South Korea as Determined by Multilocus Sequence Typing.

Orientia tsutsugamushi, an obligate intracellular organism, is the causative agent of scrub typhus. Multilocus sequence typing (MLST) is a genetic typing method that provides a unified bacterial isolate characterization approach. However, there are no comparative studies in South Korea on the genotypic properties of O. tsutsugamushi based on MLST. To conduct a comparative analysis with previous data collected from Thailand, Laos, and Japan, we investigated the genetic diversity of O. tsutsugamushi from 51 patients with scrub typhus in South Korea by using MLST. The MLST analysis revealed 10 new alleles in the housekeeping genes: gpsA, n = 2; mdh, n = 1; nrdB, n = 1; nuoF, n = 1; ppdK, n = 1; sucB, n = 2; and sucD, n = 2. These novel alleles led to the assignment of six new sequence types (STs) (ST93-98). The 51 samples corresponded to seven different STs (ST48 and ST93-98), with ST48 accounting for the largest proportion (49.0%) of O. tsutsugamushi STs in South Korea. Interestingly, O. tsutsugamushi from patients with scrub typhus in South Korea were clustered in two different clades, and the five Korean STs (ST48, ST93, ST94, ST95, and ST98) were close genetically to ST80, which was isolated from Laos. The remaining two STs (ST96 and ST97) were close genetically to ST49 (Ikeda, Japan). Overall, our results suggest that the relative genetic stability and the clonal populations of O. tsutsugamushi strains in South Korea have remained mostly conserved.