Early cidofovir administration might be associated with a lower probability of respiratory failure in treating human adenovirus pneumonia: a retrospective cohort study.

OBJECTIVE: To compare outcomes of early and delayed treatment with cidofovir for human adenovirus (HAdV) pneumonia. METHODS: A retrospective cohort study in Korean military hospitals was conducted between January 2012 and December 2018. Patients with potentially severe HAdV pneumonia with risk factors for respiratory failure were included and divided into early (within 7 days from symptom onset) and delayed (after 7 days from symptom onset) treatment groups. The primary outcome was respiratory failure development within 21 days after symptom onset. RESULTS: A total of 89 patients with potentially severe HAdV pneumonia were enrolled in the cohort; they included 62 early and 27 delayed treatment patients. All patients were males in their early 20s. Significantly fewer patients in the early treatment group progressed to respiratory failure (8/62, 12.9%), compared to the delayed group (18/27, 66.7%, p < 0.001). Early treatment was associated with a lower 21-day probability of respiratory failure by the Kaplan-Meier method (p < 0.001). On multivariate analysis, monocyte count, hypoxaemia, confusion, whole lung involvement, and early cidofovir treatment within 7 days from symptom onset were included, and monocyte count (HR 0.995, 95%CI 0.991-1.000, p 0.042), confusion (HR 4.964, 95%CI 1.189-20.721, p = 0.028), and early cidofovir treatment (HR 0.319, 95%CI 0.115-0.883, p = 0.028) were significantly associated with respiratory failure. CONCLUSIONS: Early administration of cidofovir was associated with a lower hazard for respiratory failure development. It is suggested that cidofovir be administered within 7 days from symptom onset to prevent respiratory failure in patients with potentially severe HAdV pneumonia.

Impact of appropriateness of empiric therapy on outcomes in community-onset bacteremia by extended-spectrum-ß-lactamase producing Escherichia coli and Klebisella pneumoniae definitively treated with carbapenems.

Despite a significant increase of bloodstream infection caused by extended-spectrum-ß-lactamase (ESBL)-producing Enterobacteriaceae in the community-setting, information regarding clinical outcomes of inappropriate empiric therapy (IAT) in patients with those infections is limited. A multicenter-retrospective cohort study was conducted in four hospitals. A total of 249 adults were identified to have community-onset bacteremia caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae, and definitively treated with carbapenems. According to the appropriateness of empiric therapy, individuals were divided into an appropriate empiric therapy (AT) group (n = 106) and IAT group (n = 143). Patients who received AT showed more severe underlying conditions including underlying solid cancer, healthcare-association and intensive care unit (ICU) care, compared to the IAT group. Primary bacteremia was more commonly found in the AT group than in the IAT group, while urinary tract infection predominated more frequently in the IAT group than in the AT group. Multivariate analysis using propensity score analysis indicated that inappropriateness of empiric therapy was not an independent risk factor for 30-day death. ICU care, respiratory tract infection and underlying liver, renal and connective tissue diseases were significantly associated with mortality. In patients with bloodstream infections caused by ESBL-producing E. coli and K. pneumoniae in the community-setting, delay in appropriate therapy was not associated with an increased rate of death if the patients were definitively treated with carbapenems.

Generic piperacillin/tazobactam is not associated with galactomannan false-positivity in adult patients with cancer: a case-control study.

Recent products of piperacillin/tazobactam (PTZ) from the original manufacturer, previously considered a major cause of galactomannan (GM) false-positivity, are reported not to be related to it. However, data regarding generic PTZ are limited and controversial. To evaluate the effect of generic PTZ on GM false-positivity in Korea, we performed a case-control study in adult patients with cancer. A case-control study was designed. Electronic medical records of cancer patients who were admitted and tested for serum GM between March and June 2014 at a tertiary care university hospital were reviewed. During the study period, a single generic PTZ (C manufacturer, Korea) was used. Patients who received PTZ within 24 h prior to serum GM testing were enrolled. Age- and GM test date-matched non-PTZ patients were selected as controls. A total of 110 patients received PTZ within 24 h prior to serum GM testing during the study period. The GM optical density index (ODI) of the PTZ group did not vary significantly from that of the control group (p = 0.251). The percentage of false-positive patients in the PTZ group was also similar to that of the control group (p = 0.538). There was no statistical relationship between GM ODI titer and time interval from PTZ administration (p = 0.095) or cumulative PTZ dose (p = 0.416). In a case-control study that evaluated 220 patients, a generic PTZ in Korea was not related to GM false-positivity.

Risk factors for cytomegalovirus gastrointestinal diseases in adult patients with cancer.

Cytomegalovirus (CMV) gastrointestinal (GI) disease has been noticed frequently in cancer patients, causing abdominal pain, diarrhea, and GI bleeding. However, little is known about its actual incidence, clinical presentation, and the risk factors for its development among cancer patients. To answer these questions, we analyzed all cases that occurred during an 18-year period at our center. A case-control study was performed to identify risk factors for CMV GI disease. Electronic medical records were reviewed from individuals who were admitted and diagnosed with CMV GI disease during the period of January 1995 through March 2013 at a tertiary care center. Two CMV disease-free cancer patients were matched as controls. A total of 98 episodes of CMV GI disease were included in this study, and the overall incidence rate was 52.5 per 100,000 cancer patients, with an increasing trend throughout the study period. According to multivariate analysis, male sex, low body mass index, lymphopenia, hematological malignancy, and steroid use and red blood cell transfusion within 1 month prior to the CMV disease were identified to be independent risk factors. Among these factors, RBC transfusion showed the highest odds ratio (OR = 5.09). Male sex, low body mass index, lymphopenia, hematological malignancy, steroid use, and red blood cell transfusion within 1 month prior to the CMV disease diagnosis were independent risk factors for the development of CMV GI disease in adult patients with cancer.

Impact of acute kidney injury on mortality and medical costs in patients with meticillin-resistant Staphylococcus aureus bacteraemia: a retrospective, multicentre observational study.

BACKGROUND: Despite the frequent occurrence of acute kidney injury (AKI) associated with meticillin-resistant Staphylococcus aureus (MRSA) infection during treatment, the adverse impact of renal injury on clinical and economic outcomes has not been evaluated. AIM: To study the clinical and economic burdens of MRSA bacteraemia and the impact of AKI occurring during treatment on outcomes. METHODS: Medical records of patients hospitalized for MRSA bacteraemia between March 2010 and February 2011 in eight hospitals in Korea were reviewed retrospectively to evaluate the risk factors for AKI and mortality. Direct medical costs per patient of MRSA bacteraemia during treatment were estimated from the medical resources consumed. FINDINGS: In all, 335 patients were identified to have MRSA bacteraemia. AKI occurred in 135 patients (40.3%) during first-line antibiotic therapy. Independent risk factors for AKI were male sex, underlying renal disease, intra-abdominal and central venous catheter infection, and increase in Pitt bacteraemia score. Seventy-seven (23.0%) patients died during the study period. Underlying solid tumour, high Pitt bacteraemia score, and occurrence of AKI were independent risk factors for mortality. The mean total medical cost per MRSA patient was estimated as South Korean Won 5,435,361 (US$4,906), and occurrence of AKI and ICU admission were identified as independent predictors of increased direct medical costs. Compared with patients who retained their baseline renal function, patients with AKI had a 45% increase in medical costs. CONCLUSIONS: Patients who developed AKI showed significantly higher mortality rate and greater direct medical costs compared with patients who retained baseline renal function.

Risk factors for treatment failure in patients with prosthetic joint infections.

A retrospective, observational cohort study was conducted to describe the incidence, clinical and microbiological findings and to evaluate risk factors for treatment failure associated with prosthetic joint infections (PJIs). We retrospectively reviewed the medical records of all patients undergoing total knee or total hip prosthesis implantation in our institution between 1994 and 2008. Our institution is a 1950-bed tertiary care university hospital and referral centre. A total of 93 patients with PJIs was identified although only 68 patients had undergone prosthesis implantation at our hospital. The overall infection rate was 0.63%. The most common organisms isolated were Gram positive (76.5%), including meticillin-resistant staphylococci. Two-stage arthroplasty was performed in 48 (51.6%) patients, and debridement and retention of the prosthesis in 34 (36.5%) patients. When 43 patients followed up for more than two years after treatment were included in treatment outcome analysis, the overall treatment failure rate was 41.8% (18/43). Staphylococcus aureus infection was the only clinical variable associated with treatment failure (odds ratio: 11.9; 95% confidence interval: 1.07e133.9; P = 0.044), after adjustment for the other variables. In conclusion, S. aureus was the most common pathogen isolated in patients with PJI, and an independent risk factor for treatment failure in patients with PJI.

Inappropriate initial antimicrobial therapy as a risk factor for mortality in patients with community-onset Pseudomonas aeruginosa bacteraemia.

This study was performed to identify the risk factors for mortality and evaluate the effect of inappropriate initial antimicrobial therapy on the outcomes of patients with community-onset Pseudomonas aeruginosa bacteraemia in an emergency department (ER) setting. All cases with P. aeruginosa bacteraemia occurring within 48 h after ER visit from January 2000 to December 2005 were retrospectively analysed. A total of 106 community-onset P. aeruginosa bacteraemia cases in the ER were included (mean age, 57.61 +/- 14.44 years old; M:F, 58:48). Although P. aeruginosa bacteraemia was diagnosed in the ER, most of the cases of P. aeruginosa bacteraemia were healthcare-associated (88.7%). Malignancy (n = 83, 78.3%) was the most common underlying disorder. Fifty patients (47.2%) were neutropaenic and 56 patients (52.8%) had septic shock. The overall 30-day mortality rate was 26.4% (28/106). In the univariate analysis, underlying malignancy, high Charlson's weighted index of comorbidity (> or = 3), high Pitt bacteraemia score (> or = 4), indwelling central venous catheter and inappropriate initial therapy were significantly associated with 30-day mortality (all P < 0.05). In the multivariate analysis, high Pitt bacteraemia score (OR, 17.03; 95% CI, 4.60-63.15; P < 0.001) and inappropriate initial antimicrobial therapy (OR, 4.29; 95% CI, 1.39-13.24; P = 0.011) were found to be significant risk factors for 30-day mortality. The 30-day mortality rate was significantly higher in the inappropriate therapy group (18/51, 35.3%) than in the appropriate therapy group (10/55, 18.2%) (P = 0.046). This study demonstrated that inappropriate initial antimicrobial therapy was significantly associated with unfavourable outcomes in patients with community-onset P. aeruginosa bacteraemia. As P. aeruginosa bacteraemia can be a fatal infection, even when community-onset, inappropriate antimicrobial therapy should be avoided in suspected cases of P. aeruginosa bacteraemia.

Clinical outcomes and risk factors of community-acquired pneumonia caused by gram-negative bacilli.

To identify specific risk factors and clinical outcomes of community-acquired pneumonia (CAP) caused by gram-negative bacilli (GNB), we compared the clinical features and outcomes of patients with CAP due to GNB with those of patients with non-GNB pneumonia. We performed a prospective observational study of 912 cases of adult CAP in Asian countries from January 2002 to December 2004. Systemic laboratory evaluation for determining the etiology and clinical evaluation were performed. Of 912 cases with CAP, 93 (10.1%) cases were caused by GNB: 59 with K. pneumoniae, 25 P. aeruginosa, 7 Enterobacter species, 1 Acinetobacter baumannii, and 1 Serratia marcescens. CAP caused by GNB was more frequently associated with septic shock, malignancy, cardiovascular diseases, smoking, hyponatremia, and dyspnea, according to multivariate analysis (P < 0.05). Overall 30-day mortality rate was 7.3% (65/885). Mortality was significantly higher in the GNB group than in the non-GNB group [18.3% (17/93) vs. 6.1% (48/792); P < 0.001]. GNB as a causative microorganism was found to be one of the independent risk factors for mortality (adjusted OR = 2.63, 95% CI 1.02-6.78, P = 0.046) with nursing home residence, mechanical ventilation, cardiovascular disease, respiratory rate > 30/min, and hyponatremia (all P < 0.05). GNB was not only a frequent etiology of severe CAP but also an independent risk factor for mortality. Data suggest that an initial empirical antimicrobial coverage of GNB including P. aeruginosa should be seriously considered in cases of severe pneumonia, especially in patients with underlying malignancy, underlying cardiovascular diseases, smoking, septic shock, and hyponatremia.

Increased risk of peristomal wound infection after percutaneous endoscopic gastrostomy in patients with diabetes mellitus.

BACKGROUND: Results of prospective studies on the effect of prophylactic antibiotics before percutaneous endoscopic gastrostomy are conflicting. Factors for increased risk of peristomal wound infection have not been clearly identified. AIM: To evaluate the incidence of complications of percutaneous endoscopic gastrostomy and to determine the predictors of wound infection. PATIENTS AND METHODS: Percutaneous endoscopic gastrostomy was performed on 134 patients in different disease groups between January 1996 and June 2000. Medical records were carefully reviewed for demographic data, indications for percutaneous endoscopic gastrostomy, use of prophylactic antibiotics, complications and comorbid conditions predisposing to wound infection. RESULTS: Of 134 patients, 22 (16.4%) developed complications after percutaneous endoscopic gastrostomy Wound infection, the most common complication, occurred in 19 patients (14.2%) and Pseudomonas aeruginosa was the most frequently isolated microorganism. In univariate analysis, non-malignant disease and diabetes mellitus were significantly associated with peristomal wound infection after percutaneous endoscopic gastrostomy. In multivariate analysis, only diabetes mellitus was an independent risk factor for the development of peristomal wound infection after percutaneous endoscopic gastrostomy (p = 0.035) CONCLUSIONS: Patients with diabetes mellitus have a higher risk of peristomal wound infection after percutaneous endoscopic gastrostomy.

Routine pharyngeal cultures may not be useful in pediatric victims of sexual assault.

INTRODUCTION: This study was conducted to determine the usefulness of routine pharyngeal cultures in pediatric sexual assault victims. METHODS: A retrospective chart review was conducted to examine incidence data. The study was conducted in a 656-bed tertiary care hospital with 60,000 ED visits and approximately 350 pediatric sexual assault examinations annually. Records of all pediatric sexual assault examinations completed between 12:01 AM January 1, 1994, and 12:01 AM January 1, 1997, were retrospectively reviewed for inclusion. Subjects were included if they were younger than 15 years and had a nonacute examination for a suspected sexual assault. The final sample included 370 females and 81 males (total n=451 children). Oral and anal cultures were obtained on all patients. In addition, female patients had vaginal cultures and male patients had penile cultures performed. Culture specimens were sent for detection of chlamydia and gonococcus organisms. RESULTS: Of the 451 sets of cultures examined, there were 6 patients with one or more positive culture results. The 6 patients yielded a total of 10 positive culture results: 1 anal only, 1 vaginal only, and 4 both anal and vaginal. This was a positive culture rate of 1.3% overall. The positive culture result rates by site were oral 0%, vaginal 1.6%, anal 1.1%, and penile 0%. The ages of patients with positive culture results ranged from 2 to 13 years; all of those with positive culture results were female. DISCUSSION: The incidence of positive oral culture results in this sample was zero. This finding supports a more limited approach to standard sexually transmitted disease screening in pediatric sexual assault victims. The elimination of routine oral cultures in pediatric victims without alleged oral contact decreases the examination time, decreases the number of invasive procedures associated with the examination, and decreases the cost of the examination without negatively affecting patient care.

Upstream elements required for expression of nucleoside triphosphate hydrolase genes of Toxoplasma gondii.

Nucleoside triphosphate hydrolase is an abundant protein secreted by the obligate protozoan parasite Toxoplasma gondii. The protein has apyrase activity, degrading ATP to the di- and mono-phosphate forms. Because T. gondii is incapable of de novo synthesis of purines, it is postulated that NTPase may be used by the parasite to salvage purines from the host cell for survival and replication. To elucidate the molecular mechanisms of NTP gene expression, we isolated from the virulent RH strain of T. gondii the putative promoter region of three tandemly repeated NTP genes (NTP1, 2, 3). Using deletion constructs linked to the chloramphenicol acetyl transferase (CAT) reporter gene, we defined an active promoter within the first 220 bp. Sequence analysis of this region reveals the lack of a TATA box, but the promoter region is associated with a sequence which resembles an initiator element (Inr) in the NTP1 and NTP3 genes. This sequence which is similar to other Inrs known to regulate the expression of a wide variety of RNA polymerase II genes, is required for NTP expression. The NTP3 promoter contains sufficient information for developmentally regulated expression of CAT activity when the actively replicating stage tachyzoite differentiates into the dormant bradyzoite form.