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S C Chang

Publications and source records attributed to S C Chang.

At least 55 records · Page 3Linked to original sources
PubMed2001

Usefulness of the suspended microbubble sign in differentiating empyemic and nonempyemic hydropneumothorax.

OBJECTIVE: The suspended microbubble sign is defined as the image seen on ultrasonography consisting of a pleural effusion strewn with numerous hyperechoic pinpoints and more or less linear shadows that move synchronously with respiration. In this study, we intended to evaluate the clinical usefulness of the suspended microbubble sign in differentiating empyemic and nonempyemic hydropneumothorax. METHODS: This series consisted of 8 patients with empyemic hydropneumothorax and 23 patients with nonempyemic hydropneumothorax. The finding of the presence of the suspended microbubble signs on ultrasonography was recorded. To further elucidate the generation of the suspended microbubble sign, the interaction between air and pleural fluid of different types was investigated in vitro. RESULTS: The suspended microbubble sign was shown on ultrasonography in all 8 patients with empyemic hydropneumothorax but was absent in the 23 patients with nonempyemic hydropneumothorax. These findings were supported by the observation that the pus seemed to mix with and trap the air more easily than did the nonpurulent pleural fluid, as shown in vitro. In this selected population, the sensitivity and specificity of the suspended microbubble sign in aiding a diagnosis of empyemic hydropneumothorax were both 100%. CONCLUSION: The suspended microbubble sign shown on ultrasonography might be of considerable value in differentiating empyemic and nonempyemic hydropneumothorax.

Diagnosis, Differential↗
PubMed2001

Dietary fish oil increases CD8+ T-cells and decreases autoreactive T-cell activity in autoimmune NZB/W F1 mice.

To further elucidate the effect of different dietary fats on the pathogenesis of autoimmune diseases, five groups of New Zealand black/white (NZB/W) F1 mice were fed diets containing 200 g of different dietary fats including palm oil, lard-soybean oil (1:1, w/w), soybean oil, canola oil or fish oil. Serum levels of anti-DNA antibodies, proteinuria were followed every month and life span of the mice was determined. After 5 months of the respective diets, mice were killed at the age of 7 months and phenotypic analysis of splenic cells and peritoneal resident cells was performed. The pattern of production of cytokines in splenic T-cells was also investigated. The peritoneal resident cells were isolated for measurement of prostaglandin E2 (PGE2) levels. Significantly lower immunoglobulin G (IgG) anti-single-stranded DNA (ssDNA) and anti-double-stranded DNA (dsDNA) antibody levels were associated with less severe proteinuria and prolonged life span in mice fed dietary fish oil compared to mice fed other dietary oils. Phenotypic analysis of spleen cells showed increased CD8+ T-cells in the mice fed dietary fish oil compared to mice of the other dietary groups, and the percentage of natural killer (NK) cells in the mice fed dietary fish oil was also higher compared to the other dietary groups. The peritoneal resident cells produced lower PGE2 in mice fed fish oil compared to mice in the other dietary groups. To further investigate the effect of fish oil on autoreactive T-cells, splenic T-cells purified using a nylon wool column were stimulated with non-T-cells of young NZB/W F1 mice. Our data suggest that the anti-DNA antibody augmentation ability of T-cells in mice fed dietary fish oil was significantly decreased compared to mice in the other dietary groups. These data indicate that dietary fish oil might maintain the existence of CD8+ T-cells, decrease autoreactive T-cell activity and alleviate subsequent autoimmune processes in autoimmune prone NZB/W F1 mice.

Animals↗
PubMed2001

Perfusionist-transmitted bacterial mediastinitis in a heart transplant recipient.

We report the case of a 56-year-old man who developed bacterial mediastinitis with methicillin-resistant Staphylococcus aureus after undergoing heart transplantation. He had a history of insulin-dependent diabetes mellitus and prior cardiac surgery. To find the source of nosocomial infection, we cultured nasal swab specimens from all hospital personnel involved in this operation. We used antibiotic sensitivity profiling and pulsed-field gel electrophoresis to subtype the involved microorganism. The S. aureus isolates from the patient and the perfusionist were identical to each other and were different from the strains previously found in our hospital. It is almost certain that the S. aureus mediastinitis in this patient was transmitted from the perfusionist. We recommend obtaining cultures from hospital staff members when there is an outbreak of staphylococcal infection.

Bacteriological Techniques↗
PubMed2001

Antibiotic use in public hospitals in Taiwan after the implementation of National Health Insurance.

BACKGROUND AND PURPOSE: Only limited data is available on the patterns of antibiotic use in hospitals in Taiwan before and after the implementation of national health insurance. This study aimed to determine the patterns of use of antibiotics in public hospitals in Taiwan after the implementation of the National Health Insurance program and to compare these with patterns prior to the implementation. METHODS: Data on the annual use of all antibiotics in public hospitals in Taiwan during the period from fiscal year (FY) 1994-1995 to 1997-1998 were collected and analyzed. Hospitals included seven medical centers, 19 regional hospitals, 53 district hospitals, and eight specialty service hospitals. RESULTS: The annual cost of antibiotics made up 17.4% of the annual cost of all medication used in these hospitals in FY 1994-1995, and decreased year by year to 12.6% in FY 1997-1998. During the study period, 57.4% of the total cost of antibiotics were incurred by medical centers, 24.6% by regional hospitals, 16.2% by district hospitals, and 1.8% by specialty service hospitals. The most commonly used class of antibiotic was cephalosporins, accounting for 48.0% to 54.3% of total antibiotic costs. The second most commonly used class of antibiotic was penicillins, accounting for 15.9% to 17.4% of total antibiotic costs. In FY 1994-1995, the next most commonly used classes of antibiotics were aminoglycosides, fluoroquinolones, and other beta-lactams, respectively, but by FY 1997-1998 these had changed to fluoroquinolones, glycopeptides, and aminoglycosides, respectively. Among the various cephalosporins used, first-generation cephalosporins accounted for 76.1% of all cephalosporins used in FY 1994-1995, which increased year by year to 84.0% in FY 1997-1998. Second-generation cephalosporins accounted for 20.7% of all cephalosporins used in FY 1994-1995, decreasing to 13.2% in FY 1997-1998. CONCLUSION: The introduction of the National Health Insurance program in Taiwan brought about a major change in antibiotic use patterns in public hospitals.

Anti-Bacterial Agents↗
PubMed2001

In vitro activity of moxifloxacin against common clinical bacterial isolates in Taiwan.

The in vitro antimicrobial activities of moxifloxacin were compared with 7 other antimicrobial agents. A total of 707 isolates of 11 common pathogenic bacteria were collected from the National Taiwan University Hospital; antimicrobial activities against these isolates were evaluated by minimum inhibitory concentration using an agar-dilution method. Most common pathogenic bacteria were susceptible to moxifloxacin, including methicillin-susceptible and -resistant Staphylococcus aureus, methicillin-susceptible and -resistant Staphylococcus epidermidis, Streptococcus pneumoniae, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Pseudomonas aeruginosa, Burkholderia cepacia, Acinetobacter baumannii, and Stenotrophomonas maltophilia. For many of these bacterial species, moxifloxacin was the most active antimicrobial agent compared with the third- and fourth- generation cephalosporins, carbapenems, monobactam, and other quinolones. Some strains of methicillin-resistant S. aureus and methicillin-resistant S. epidermidis demonstrated very low levels of minimum inhibitory concentration for moxifloxacin, suggesting the potential application of the drug to treat some drug-resistant gram-positive bacterial infections. Moxifloxacin was less active against P. aeruginosa, but was more active against S. maltophilia when compared with other fluoroquinolones. In conclusion, moxifloxacin exhibits an increased potency against gram-positive bacteria as compared with other tested antimicrobial agents, while preserving excellent activity against gram-negative bacteria. The drug appears to be a promising agent expressing activity against a wide variety of bacteria in Taiwan.

Anti-Bacterial Agents↗
PubMed2001

Risk factors for ICU mortality in critically ill patients.

BACKGROUND AND PURPOSE: Advances in critical care medicine have increased the chances of survival for patients with severe illness or trauma. However, such patients consume a large proportion of medical resources. This study sought risk factors for mortality that have potential to be modified among patients treated in medical or surgical intensive care units (ICUs). METHODS: This 6-month prospective observational study was conducted in the medical and surgical ICUs of an 1,800-bed university hospital. All adult patients with an expected ICU stay of 48 hours or more were followed up regularly until discharge from the ICUs, or for 10 weeks during their stay in ICUs. RESULTS: Of 342 patients enrolled, 77 (22.5%) died during a median follow-up period of 5 days (range, 2-70 days). Among a range of variables at the time of ICU entry or developing during stay in ICUs, 17 were associated with higher mortality rate. Multivariate analysis using a logistic regression model demonstrated that the presence of systemic inflammatory response syndrome (SIRS) at the time of ICU entry (adjusted relative risk, ARR, 2.85; 95% confidence interval, CI, 1.16-7.05), Acute Physiological and Chronic Health Evaluation (APACHE) II score on ICU Day 4 (ARR 1.12 with increment of one score; 95% CI 1.01-1.24), Therapeutic Intervention Scoring System (TISS) score on Day 4 (ARR 1.13 with increment of one score; 95% CI 1.05-1.23), parenteral nutrition (ARR 4.97, 95% CI 1.73-14.26), and nosocomial Candida infection (ARR 3.39, 95% CI 1.12-10.23) were independently associated with ICU mortality. CONCLUSIONS: In addition to SIRS and the APACHE II and TISS scores, this study found that nosocomial Candida infection and parenteral nutrition were independently associated with mortality after control for admission conditions, severity of illness scores, and interventions.

Adolescent↗
PubMed2001

Plate atelectasis: an implication of foreign body aspiration into the lower airways in two adults.

Pneumonic patches and atelectatic or bronchiectatic changes in the tributary lung distal to the bronchial foreign body are common radiographic abnormal findings in adults with foreign body aspiration into the lower airways. Nevertheless, plate (plate-like or discoid) atelectasis, a form of peripheral atelectasis, has not been reported to associate with this condition. In this report, we describe two men with the foreign body impacted in the right intermediate bronchus. In both cases, plate atelectasis was found in the base of the right lung and disappeared after successful removal of the foreign body via fiberoptic bronchoscopy. These two cases illustrate that plate atelectasis may be an implication of foreign body aspiration into the lower airways.

Aged↗
PubMed2001

Molecular epidemiology of Candida colonizing critically ill patients in intensive care units.

BACKGROUND AND PURPOSE: Nosocomial Candida infections are an important cause of morbidity and mortality in critically ill patients. Although there is growing evidence that candidemia develops primarily as a consequence of endogenous colonization, hospital outbreaks of Candida infection are not uncommon. To examine the prevalence and consequence of Candida colonization in critically ill patients and to elucidate the contribution of cross-transmission to the high frequency of nosocomial fungal infection in intensive care units (ICUs), a 6-month prospective surveillance study was conducted. PATIENTS AND METHODS: A total of 342 adult patients with an expected ICU stay of 48 hours or more were enrolled in the study. Surveillance cultures were taken from the rectal region, oropharynx, and urine on ICU entry and weekly thereafter. The electrophoretic karyotypes (EKs) of all isolates were characterized using pulsed-field gel electrophoresis. RESULTS: A total of 873 Candida strains were isolated from 208 of the 342 patients (60.8%) during ICU stay. A comparison of the EK patterns generated from Candida strains isolated from different patients demonstrated a variability of karyotypes, and failed to identify predominant clones colonizing or infecting ICU patients. For 62 of 102 patients colonized with multiple isolates of the same Candida spp., the EK patterns of the Candida strains isolated from individual patients were identical or similar, even when isolated from different anatomical sites, and the patterns remained the same for up to 62 days. A total of 57 episodes of Candida infection occurred in 53 (25.5%) of these 208 patients. Thirty-six episodes (63.1%) of Candida infection were preceded by colonization with the same Candida spp. All infecting strains had identical or similar EK patterns to prior colonizing strains. CONCLUSIONS: While Candida colonization was common in ICU patients, karyotyping did not identify cross-transmission among these patients. Further, only 25.5% of patients with Candida colonization subsequently developed Candida infection. These findings suggest that universal prophylaxis is not warranted in critically ill patients with Candida colonization.

Candida↗
PubMed2001

Invasive infections due to vancomycin-resistant enterococci in adult patients.

Since 1990, vancomycin-resistant enterococci have emerged as important nosocomial pathogens. Invasive infections caused by these organisms have challenged most physicians because they are resistant to multiple antibiotics. We analyzed the clinical characteristics of adult patients with invasive vancomycin-resistant enterococci infections in the National Taiwan University Hospital from January 1993 through December 2000. A total of 11 adult patients were identified, 9 of whom had bacteremia (7 caused by vancomycin-resistant Enterococcus faecalis and 2 by vancomycin-resistant Enterococcus faecium) and one each had thoracic empyema (vancomycin-resistant E. faecium) and peritonitis (vancomycin-resistant E. faecium). Five patients had rectal swab cultures positive for vancomycin-resistant enterococci; 4 of them had underlying malignancies. The majority (91%) of these patients had prolonged hospitalization and prior long-term use of broad-spectrum cephalosporins (ceftriaxone, ceftazidime, or cefepime) or anti-anaerobic agents (clindamycin or metronidazole). The crude mortality rate was 64%. In conclusion, invasive infection caused by vancomycin-resistant enterococci is an emerging problem among hospitalized patients in Taiwan, particularly those with severe underlying diseases and exposure to multiple antibiotics.

Adult↗
PubMed2000

A novel chromosome region maintenance 1-independent nuclear export signal of the large form of hepatitis delta antigen that is required for the viral assembly.

Hepatitis delta virus (HDV) is a satellite virus of hepatitis B virus, as it requires hepatitis B virus for virion production and transmission. We have previously demonstrated that sequences within the C-terminal 19-amino acid domain flanking the isoprenylation motif of the large hepatitis delta antigen (HDAg-L) are important for virion assembly. In this study, site-directed mutagenesis and immunofluorescence staining demonstrated that in the absence of hepatitis B virus surface antigen (HBsAg), the wild-type HDAg-L was localized in the nuclei of transfected COS7 cells. Nevertheless, in the presence of HBsAg, the HDAg-L became both nuclei- and cytoplasm-distributed in about half of the cells. An HDAg-L mutant with a substitution of Pro-205 to alanine could neither form HDV-like particles nor shift the subcellular localization in the presence of HBsAg. In addition, nuclear trafficking of HDAg-L in heterokaryons indicated that HDAg-L is a nucleocytoplasmic shuttling protein. A proline-rich HDAg peptide spanning amino acid residues 198 to 210, designated NES(HDAg-L), can function as a nuclear export signal (NES) in Xenopus oocytes. Pro-205 is critical for the NES function. Furthermore, assembly of HDV is insensitive to leptomycin B, indicating that the NES(HDAg-L) directs nuclear export of HDAg-L to the cytoplasm via a chromosome region maintenance 1-independent pathway.

Active Transport, Cell Nucleus↗
PubMed2000

Restoration of cellular immunity against tuberculosis in patients coinfected with HIV-1 and tuberculosis with effective antiretroviral therapy: assessment by determination of CD69 expression on T cells after tuberculin stimulation.

Whether immunity against opportunistic pathogens can be fully restored by control of HIV-1 replication remains open to question. This longitudinal study was conducted to measure anti-tuberculosis (TB) cellular immunity in 13 HIV-1/TB-coinfected patients effectively treated by highly active antiretroviral therapy (HAART) in a period of 12 months. In this study, anti-TB cellular immunity was assessed by determining the frequencies of CD 69 expression on CD4+ and CD8+ T cells in response to purified protein derivative (PPD) stimulation (abbreviated as %CD4+CD69 to PPD and %CD8+CD69 to PPD). Here, we show that %CD4+CD69 to PPD correlated with the results of tuberculin skin tests and interferon-gamma (IFN-gamma) production from PPD-stimulated CD4+ T cells, and %CD8+CD69 to PPD also correlated with CD8+ T cell-mediated PPD-specific cytolysis. In overall analysis for these 13 patients, both %CD4+CD69 to PPD and %CD8+CD69 to PPD increased significantly during the 12 months (p =. 003 and p <.001, respectively). However, we found %CD4+CD69 to PPD or %CD8+CD69 to PPD failed to increase substantially in some patients (i.e., immunologic nonresponders). A significantly higher proportion of patients whose baseline CD4+ count was <50 cells/mm3 were considered to be CD4+ nonresponders compared with those whose baseline CD4+ count was >50 cells/mm3. Furthermore, baseline CD4+ cell count in nonresponders is significantly lower than that in responders, although the effectiveness of HAART did not differ between them. Our results indicate that PPD-specific frequencies of CD69 expression may be used as surrogate markers of anti-TB cellular immunity. By this method, we show that full reconstitution of anti-TB cellular immunity in HIV-1/TB coinfected patients may not necessarily be achieved by "successful" HAART and may be influenced by the baseline immune status when HAART is started. These data suggest that the decision to discontinue secondary prophylaxis for opportunistic infections should be cautiously made, even when the CD4+ cell count has significantly increased.

AIDS-Related Opportunistic Infections↗
PubMed2000

Clinical spectrum, morbidity, and mortality of acquired immunodeficiency syndrome in Taiwan: a 5-year prospective study.

The clinical spectrum of AIDS and changes of morbidity and mortality associated with HIV infection following initiation of highly active antiretroviral therapy (HAART) are rarely described in the less developed countries in the Asia-Pacific region. We prospectively observed on a follow-up basis 309 HIV-infected patients (82.8% with AIDS) at National Taiwan University Hospital in Taiwan, where highly active antiretroviral therapy (HAART) has been provided to all patients at no charge at any stage of HIV infection since April 1, 1997, to describe the spectrum of HIV-associated opportunistic diseases and evaluate changes of morbidity and mortality from June 24, 1994 through June 23, 1999. Of the patients, 59.3% at study entry had a CD4+ lymphocyte count of <50 cells/microliter. The five leading HIV-associated opportunistic infections included oroesophageal candidiasis (195 patients), Pneumocystis carinii pneumonia (93), tuberculosis (77), mucocutaneous herpes simplex infection (74), and cytomegalovirus diseases (73). The incidence rates of seven major AIDS-defining opportunistic diseases were declining though the changes of the relative proportions varied. The median duration of hospitalization decreased from 36 days in 1995 to 12 days in 1999 (p =.0001). Overestimated mortality rate declined from 148.4 per 100 patient-years in 1995 to 7.4 per 100 patient-years in 1999 (p =.0001) whereas the underestimated mortality rate declined from 110.5 to 5.39 per 100 patient-years (p =.0001). Risk ratio (RR) for mortality in patients who received HAART compared with those who did not was 0.410 (95% confidence interval [CI], 0.249-0.674; p =.0004) and the RR was 0.250 (95% CI, 0.127-0.492; p =.0001) when the analysis was limited to patients with an initial CD4+ lymphocyte count <100 cells/microliter and follow-up duration >30 days after adjusting for their age, gender, type of risk behavior, and CD4+ lymphocyte count. Morbidity and mortality were declining with each study year even in a population consisting mainly of patients at the advanced stage of HIV infection in Taiwan. Earlier diagnosis, accumulation of clinical experience, and use of HAART were associated with lower mortality rates.

AIDS-Related Opportunistic Infections↗
PubMed2000

Specific interaction between the hepatitis delta virus RNA and glyceraldehyde 3-phosphate dehydrogenase: an enhancement on ribozyme catalysis.

Replication of hepatitis delta virus (HDV) RNA occurs in the nuclei of infected cells. The replication is mediated by cellular factors containing an RNA polymerase II-like enzyme activity through a double rolling-circle mechanism and is regulated by delta antigens. In this study, UV cross-linking experiments were carried out to examine interactions between HDV RNA and proteins present in HeLa nuclear extract. Cellular proteins with molecular mass of 23 (p23), 36 (p36), 38 (p38), and 58 (p58) kDa bound to full-length HDV RNA of both genomic and antigenomic strands. Deletion analysis on the antigenomic strand mapped the interacting domain within a 79-nucleotide fragment but not at the ends of the rod-shaped viral RNA structure. The specificity of the RNA-protein interactions was demonstrated by competition experiments and the specific HDV RNA-binding proteins were purified through column chromatography. Electrophoresis mobility shift assay with the purified fractions demonstrated that the interaction between p36 and HDV RNA was relatively stable even in the presence of 0.5 M NaCl. Biochemical analysis including protein microsequencing identified the p36 as glyceraldehyde 3-phosphate dehydrogenase (GAPDH). RNase footprinting indicated that the UC-rich domain between nucleotides 379 and 414 of the HDV antigenomic RNA was involved in the GAPDH binding. Functional studies further demonstrated an enhancing effect of GAPDH on the ribozyme activity of HDV antigenomic RNA. In addition, in the presence of HDV RNA cellular GAPDH relocalized from the cytoplasm to the nucleus where HDV replication occurs. These results suggest that GAPDH is involved in the replication of HDV.

Amino Acid Sequence↗
PubMed2000

Spontaneous bacterial empyema caused by Aeromonas veronii biotype sobria.

Spontaneous bacterial empyema is a complication of hepatic hydrothorax in cirrhotic patients. The pathogen, clinical course and treatment strategy are different to the empyema secondary to pneumonia. A 54-year-old man, who was a cirrhotic patient with hepatic hydrothorax, was admitted to National Taiwan University Hospital for fever, dyspnea and right side pleuritic pain. The image study revealed massive right pleural effusion and no evidence of pneumonia. The culture of pleural effusion yielded Aeromonas veronii biotype sobria. The diagnosis of spontaneous bacterial empyema caused by Aeromonas veronii biotype sobria was established. To our best knowledge, Aeromonas veronii biotype sobria had never been reported in English literature as the causative pathogen of spontaneous bacterial empyema.

Aeromonas↗
PubMed2000

Klebsiella pneumoniae isolates causing liver abscess in Taiwan.

Klebsiella pneumoniae has been the leading cause of pyogenic liver abscess in Taiwan during the period from 1985 to 1999, which is different from other countries. The present study investigated the in vitro antimicrobial susceptibilities of 51 K. pneumoniae isolates collected from blood cultures of patients with liver abscess in Taiwan during the period from 1993-1997, and typed by pulsed-field gel electrophoresis (PFGE). All 51 isolates were resistant to ampicillin, but susceptible to other antimicrobial agents. The minimum inhibitory concentrations (MICs) were less than 1 microg/ml for the third- and fourth-generation cephalosporins, monobactam, carbapenems, and ciprofloxacin. In comparison, 62 isolates of K. pneumoniae from community-acquired bacteremic patients without liver abscess had similar antimicrobial susceptibilities, while 142 isolates from patients with hospital-acquired bacteremia without liver abscess were much less susceptible to all of the tested antimicrobial agents. PFGE molecular epidemiologic analysis found 20 out of 51 isolates belonged to eight clusters of genetically related strains, with two or three isolates in each clusters. The other 31 isolates were genetically distinct strains. This study demonstrated that K. pneumoniae isolates which cause liver abscess in Taiwan remained susceptible to a wide range of antimicrobial agents and that they were not genetically related.

Abscess↗
PubMed2000

Evaluation of antiseptic-impregnated central venous catheters for prevention of catheter-related infection in intensive care unit patients.

Central venous catheterization represents a significant medical advancement, particularly in the treatment of critical ill. However, there is a high risk of central venous catheters-related infection. A novel antiseptic central venous catheter, made of polyurethane and impregnated with chlorhexidine and silver sulfadiazine, was developed to reduce the risk of catheters-related infection. In this study, we did a randomized clinical study to determine the efficacy by using antiseptic catheters for the prevention of central venous catheters-related infection in the intensive care units. A total of 204 patients with 235 central venous catheters were studied at the surgical intensive care units at National Taiwan University Hospital between November 1998 and June 1999. Participants received either a standard triple-lumen polyurethane catheter or an antiseptic catheter (Arrow International, Reading, Pennsylvania, USA). Both were indistinguishable from each other. Compared to standard polyurethane catheters, antiseptic catheters were less likely to be colonized by microorganisms when they were cultured at the removal (8.0 versus 20.0 colonized catheters per 100 catheters; relative risk 0.34 [95% CI, 0.15 to 0.74]; p<0.01). There was no significant differences between both groups in catheter-related infections (0.9 versus 4.9 infections per 100 catheters; relative risk 0.17 [95% CI, 0.03 to 1.15]; p = 0.07). Gram-positive cocci and fungi were more likely to colonize in the standard polyurethane catheters (p = 0.06 and 0.04, compared to antiseptic catheters respectively). Two of our cases in the control group died directly due to catheter-related candidemia. No adverse reactions such as hypersensitivity or leukopenia were found in the antiseptic catheter group. Our study showed that central venous catheters with antiseptic coating were safe and had less risk of colonization of bacteria and fungi than standard catheters in the critically ill patients.

Anti-Infective Agents, Local↗