PubMed Health⌕ Search

Biomedical subjects

Po-Ren Hsueh

Publications and source records attributed to Po-Ren Hsueh.

At least 19 recordsLinked to original sources

Isolation and characterization of strictly lytic bacteriophages against carbapenem-resistant Enterobacter cloacae complex.

UNLABELLED: The global surge of carbapenem-resistant Enterobacter cloacae complex (CR-ECC) poses a significant clinical challenge due to limited treatment options. This study aimed to isolate and characterize lytic bacteriophages (phages) targeting CR-ECC. CR-ECC CYEBC080 was used as the bacterial host for isolating lytic phages, and a comprehensive evaluation was conducted on isolated phages, including phage stability under various pH and temperature conditions, host range analysis, killing curves, and therapeutic efficacy in Galleria mellonella larvae and a murine bacteremia model. Twelve lytic phages with distinct random amplified polymorphic DNA patterns were isolated, and transmission electron microscopy confirmed their classification under the Straboviridae family within the Caudoviricetes class. All phages remained stable across pH 3-11 for up to 90 minutes, with an optimal temperature range of 25°C-37°C. Among them, CYPEBC012 exhibited the broadest host range, lysing 93.75% of 80 CR-ECC isolates, while CYPEBC006 displayed the narrowest, lysing only 65%. Whole-genome sequencing revealed 12 phages with linear double-stranded DNA genomes ranging from 177,624 to 180,648 bp. Phage treatment administered at a multiplicity of infection of 10, 1 hour post-infection, significantly improved larval survival at day 7, reaching ≥80% in most groups, except CYPEBC001 (50%) and CYPEBC004 (60%) treatment groups. In CYEBC080-infected mice, CYPEBC012 treatment resulted in 100% survival by day 3 and 80% survival through day 7. Additionally, phage-treated mice exhibited significantly reduced bacterial loads and high phage titers in blood and liver. This study demonstrates the therapeutic potential of CYPEBC012 as a promising strategy against CR-ECC infections, offering an alternative to conventional antimicrobial treatments. IMPORTANCE: This study identified and characterized lytic bacteriophages targeting carbapenem-resistant Enterobacter cloacae complex, with CYPEBC012 exhibiting the broadest host range and significantly improving survival in a murine bacteremia model. Its stability and efficacy highlight its potential for clinical application. Our findings demonstrate that phage therapy offers a promising alternative to conventional treatments to combat antibiotic-resistant infections.

Animals↗

Daptomycin susceptibility of unusual gram-positive bacteria: comparison of results obtained by the Etest and the broth microdilution method.

MICs of daptomycin, linezolid, and vancomycin against 212 isolates, including Listeria monocytogenes and Pediococcus, Leuconostoc, Rhodococcus, and Nocardia spp., were determined by the broth microdilution method; daptomycin MICs were also determined by the Etest. Except with those for Leuconostoc spp., daptomycin Etest MICs showed >90% agreement with MICs obtained by the broth microdilution method.

Culture Media↗

Disseminated tuberculosis: a 10-year experience in a medical center.

Disseminated tuberculosis remains a diagnostic challenge because the presentations are nonspecific. In the current retrospective study we describe the clinical characteristics and outcome of disseminated tuberculosis. From January 1995 to December 2004, patients with culture-confirmed tuberculosis who fulfilled the criteria for disseminated tuberculosis were selected and their medical records reviewed. Their clinical isolates were genotyped. Of the 3058 patients with culture-confirmed tuberculosis, 164 (5.4%) had disseminated disease; 14.0% of patients had acquired immunodeficiency syndrome. The most common radiographic finding was miliary lung lesions (47.0%); 31.1% of patients died at the end of the study. Poor prognostic factors included hypoalbuminemia, hyperbilirubinemia, renal insufficiency, and delayed antituberculosis treatment. Clinical findings suggestive of disseminated tuberculosis were miliary lung lesions, serum ferritin >1000 microg/L, infiltrative liver disease, and adjusted calcium >2.6 mmol/L. Simultaneously performing mycobacterial culture and histopathologic examination of bone marrow biopsy was more sensitive and faster than just performing mycobacterial blood culture in diagnosing disseminated tuberculosis. Of the 64 preserved Mycobacterium tuberculosis isolates, 47 (73.4%) were clustered and 27 (42.2%) were Beijing family. Since prognosis was worse in patients with delayed treatment, a high index of suspicion is required, especially in those with clinical findings suggestive of disseminated tuberculosis.

Adult↗

Sputum bacteriology in hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease in Taiwan with an emphasis on Klebsiella pneumoniae and Pseudomonas aeruginosa.

BACKGROUND AND OBJECTIVE: Bacterial infection is one of the major causes of acute exacerbation of COPD (AECOPD). This study was undertaken to investigate the microbiology of AECOPD. METHODS: Medical records from 494 episodes of AECOPD in patients admitted to the National Taiwan University Hospital from January 2000 to June 2004 were reviewed. Severity of COPD was classified according to the 2003 Global Initiative for Chronic Obstructive Lung Disease guideline. RESULTS: Potential pathogenic microorganisms were isolated from patients in 328 (66.4%) episodes of AECOPD. The predominant bacteria were Klebsiella pneumoniae (19.6%), Pseudomonas aeruginosa (16.8%) and Haemophilus influenzae (7.5%), followed by Acinetobacter baumannii (6.9%), Enterobacter species (6.1%) and Staphylococcus aureus (6.1%). The incidence of Streptococcus pneumoniae was 2.4%. Spirometry results obtained within 1 year of the exacerbation were available in 186 cases. K. pneumoniae was more frequently isolated in stage I COPD (39.1%) than stage II (16.6%), III (13.8%) and IV (9.4%). No glucose non-fermentative Gram-negative bacilli were isolated in stage I patients. Multivariate logistic regression analysis revealed that P. aeruginosa (odds ratio (OR) 3.19; 95% confidence interval (CI): 1.21-8.38), intubation (OR 14.81; 95% CI: 5.08-43.12) and age (OR 1.1; 95% CI: 1.03-1.17) were independent risk factors for mortality. CONCLUSIONS: Klebsiella pneumoniae and P. aeruginosa are the most common sputum pathogens in hospitalized patients with AECOPD in Taiwan, with the former being more commonly isolated from mild COPD and the latter associated with poor clinical outcome. These results should be considered when deciding which antibiotics should initially be used to treat patients with AECOPD.

Aged↗

Brain abscess associated with multidrug-resistant Capnocytophaga ochracea infection.

Brain abscesses are occasionally associated with a dental source of infection. An unusual case of frontal lobe abscess in a nonimmunocompromised child infected with multidrug-resistant Capnocytophaga ochracea is described and confirms the pathogenic potential of this organism to cause human disease in the central nervous system.

Anti-Bacterial Agents↗

Aortic valve infective endocarditis caused by Serratia liquefaciens.

Infective endocarditis of the cardiac valves caused by Serratia liquefaciens has never been reported. We describe a fatal case of aortic valve infective endocarditis caused by S. liquefaciens after intravenous injection of amphetamine, complicated by multiple organ dysfunctions.

Adult↗

Prognostic factors and antibiotics in Vibrio vulnificus septicemia.

BACKGROUND: Immunocompromised patients with Vibrio vulnificus septicemia are at high risk for fatality. When a hemorrhagic bullous necrotic cutaneous lesion (HBNCL) and decreased blood pressure develop, approximately 50% of V vulnificus septicemic patients die within 48 hours. This study aimed to evaluate the risk factor(s) for fatality among patients with V vulnificus septicemia, emphasizing the role of prescribed antimicrobial agents in general and the therapeutic efficacy of the combination of a third-generation cephalosporin and tetracycline or its analogue in particular. METHODS: Patients with the diagnosis of V vulnificus infection admitted to 5 large medical centers in Taiwan between 1995 and 2003 were included in this retrospective study. Patients were divided into 2 groups: those without [corrected] HBNCLs (group 1) [corrected] and those with [corrected] HBNCLs (group 2) [corrected]Patients were further divided into subgoups with [corrected] fatalities (fatal subgroup) and those without fatalities (nonfatal subgroup). RESULTS: A total of 93 patients participated in the study. In group 1, the fatal subgroup had higher Acute Physiology and Chronic Health Evaluation II (APACHE II) scores (P = .006) and a higher proportion of shock at arrival at the medical center (P = .015) than the nonfatal subgroup. In group 2, the effect of a first- or second-generation cephalosporin plus an aminoglycoside was negative (P = .01) and that of combined third-generation cephalosporin and tetracycline or its analogue was positive (P<.001); significant differences were found between the fatal and nonfatal subgroups in the APACHE II score (P<.001), number who were in shock at arrival at the medical center (P = .02), delayed surgical intervention (P = .03), and peripheral leukocytosis (P = .03). Shock at arrival at the medical center (odds ratio [OR], 19.25; 95% confidence interval [CI], 1.768-209.54; P = .02) was an independent risk factor for fatality in patients without HBNCLs. Use of a third-generation cephalosporin and tetracycline or its analogue significantly reduced fatality rates in patients with HBNCLs (OR, 0.037; 95% CI, 0.007-0.192; P<.001). CONCLUSION: Septic shock is a determinant of fatality in patients with V vulnificus septicemia without HBNCLs; our data suggest that the combination of a third-generation cephalosporin and tetracycline or its analogue may be a better choice in antimicrobial treatment of V vulnificus septicemic patients with HBNCLs.

APACHE↗

High frequency of linezolid-associated thrombocytopenia among patients with renal insufficiency.

This retrospective case-control study compared the tolerability and efficacy of linezolid between patients with and without renal insufficiency (serum creatinine > or =1.3mg/dL for women and > or =1.5mg/dL for men). All patients with Gram-positive infections treated with linezolid for more than 7 days were included. Data were collected from medical charts and differences between patients with and without renal insufficiency were analysed. Sixty-two patients (40 men), with a mean age of 56.9 years, were enrolled in this study. At the start of linezolid treatment, 17 patients (27.4%) had impaired renal function. Patients with renal insufficiency had a higher prevalence of diabetes mellitus compared with those with normal renal function (64.7% vs. 22.2%; P=0.002). At the start of therapy, patients with renal impairment had a higher frequency of elevated blood urea nitrogen (51.0+/-21.1mg/dL vs. 18.3+/-9.7mg/dL; P<0.001), elevated serum creatinine (2.3+/-0.7mg/dL vs. 0.9+/-0.3mg/dL; P<0.001) and decreased initial haemoglobin (9.2+/-1.5g/dL vs. 10.4+/-1.7g/dL; P=0.017). Development of severe thrombocytopenia (<100 x 10(9)/L) was significantly more common in patients with renal insufficiency (64.7% vs. 35.6%; P=0.039). The incidence of linezolid-associated thrombocytopenia was higher among patients with renal insufficiency. When patients with renal insufficiency are treated with linezolid for more than 2 weeks, the platelet count should be monitored at least twice a week owing to the increased likelihood of thrombocytopenia.

Acetamides↗

In vitro susceptibilities of aerobic and facultative Gram-negative bacilli isolated from patients with intra-abdominal infections in the Asia-Pacific region: 2004 results from SMART (Study for Monitoring Antimicrobial Resistance Trends).

In the 2004 Study for Monitoring Antimicrobial Resistance Trends (SMART), 14 centres from six countries in Asia-Pacific collected 1198 unique aerobic and facultative Gram-negative bacilli from intra-abdominal infections for susceptibility testing to 12 antimicrobial agents. Enterobacteriaceae comprised 82% of the total isolates. Escherichia coli was the most commonly isolated species (43%). Resistance rates were generally higher in Enterobacteriaceae isolated from Asian centres than those isolated from Oceania centres. There was little difference in susceptibility rates between community- and hospital-acquired Enterobacteriaceae for carbapenems. Extended-spectrum beta-lactamase (ESBL)-producers typically had a more resistant profile than non-ESBL-producers, but were usually susceptible to carbapenems. Of the antimicrobial agents tested, carbapenems were the most reliably active in vitro against Enterobacteriaceae recovered from patients in Asia-Pacific with intra-abdominal infections.

Abdomen↗

In vitro activities of various piperacillin and sulbactam combinations against bacterial pathogens isolated from Intensive Care Units in Taiwan: SMART 2004 programme data.

We investigated the in vitro activity of various piperacillin and sulbactam combinations against Gram-negative bacterial isolates from Intensive Care Units (ICUs) in Taiwan. Antimicrobial susceptibility testing of 1030 bacterial isolates recovered from ICUs of nine major teaching hospitals was performed using the agar dilution method. Sulbactam was added to piperacillin either at a fixed sulbactam concentration of 4 mg/L and 8 mg/L or at a piperacillin:sulbactam ratio of 2:1 and 4:1. Piperacillin/sulbactam at a ratio of 2:1 or a fixed 8 mg/L concentration of sulbactam had better activities against Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Serratia marcescens than other piperacillin/sulbactam formulations. For Pseudomonas aeruginosa, piperacillin/sulbactam (2:1 or 4:1 ratios) had MIC(90) values (minimum inhibitory concentration for 90% of the organisms) of 64 mg/L (>90% susceptibility) compared with 64 mg/L for cefoperazone/sulbactam (68% susceptibility) and 128 mg/L for piperacillin/tazobactam (82% susceptibility). For Acinetobacter baumannii, both piperacillin/sulbactam (either 2:1 ratio or a fixed 8 mg/L sulbactam) and cefoperazone/sulbactam were the most potent agents. Adding sulbactam to piperacillin resulted in increased susceptibility rates among piperacillin-resistant P. aeruginosa (53-57% in either 2:1 or 4:1 ratios) and A. baumannii (38-46% in either 2:1 ratio or a fixed 8 mg/L concentration of sulbactam) isolates. Results of susceptibility tests with piperacillin/sulbactam are dependent on the method used. Piperacillin/sulbactam combinations possessed better in vitro activities than piperacillin alone or piperacillin/tazobactam against P. aeruginosa and A. baumannii.

Bacteria↗

Characterization of acquired beta-lactamases and their genetic support in multidrug-resistant Pseudomonas aeruginosa isolates in Taiwan: the prevalence of unusual integrons.

OBJECTIVES: The present study was conducted to investigate acquired beta-lactamases and their genetic support in 26 Pseudomonas aeruginosa isolates that were resistant to nearly all antipseudomonal drugs from six medical centres in Taiwan. METHODS: Acquired beta-lactamases and their genetic support were determined by PCR-based strategies. RESULTS: Four and 16 of the 26 isolates were found to produce VIM-2 and VIM-3 metallo-beta-lactamases (MBLs), respectively, and 1, 1 and 2 isolates produced OXA-17, OXA-10 and PSE-1, respectively. These bla genes are all in class 1 integrons that are probably chromosomally located. The bla(VIM-3)-containing integron, with a deletion between int1 and the bla(VIM-3) structural gene, has six gene cassettes, bla(VIM-3), a probable fosfomycin resistance determinant, aacA4, aacA4, aadB and aacA4. The bla(VIM-2)-containing integron, without detectable 5'-conserved segment, contains four genes cassettes (aacA7-bla(VIM-2)-dhfr-aacA5) and is ended by tniC. The bla(OXA-10)-containing integron includes a catB3 cassette and a fused gene cassette, which is made up of bla(OXA-17) and a novel streptomycin-spectinomycin gene, designated aadA15. The bla(OXA-17)-containing integron has three gene cassettes (aacA4-catB2-bla(OXA-17)) but the 59-base element of the bla(OXA-17) cassette is interrupted by a putative transposase gene. The bla(PSE-1)-containing integron has three gene cassettes, aacA4, an aadA3-related gene designated aadA3b and bla(PSE-1). PFGE revealed genetic diversity among the multidrug-resistant isolates from different hospitals. CONCLUSIONS: This study demonstrated the high prevalence of VIM-type MBLs and the presence of unusual bla-encoding integrons in multidrug-resistant P. aeruginosa isolates in Taiwan. The spread of bla(VIM-2)-related genes by horizontal transfer might have occurred.

Anti-Bacterial Agents↗

In vitro susceptibilities of aerobic and facultatively anaerobic Gram-negative bacilli isolated from patients with intra-abdominal infections worldwide: 2004 results from SMART (Study for Monitoring Antimicrobial Resistance Trends).

OBJECTIVES: SMART (Study for Monitoring Antimicrobial Resistance Trends) is an ongoing study to monitor worldwide antimicrobial resistance trends among aerobic and facultatively anaerobic Gram-negative bacilli (GNB) isolated from intra-abdominal infections. This 2004 report summarizes the most recently completed annual data from SMART. METHODS: During 2004, 81 medical centres from 28 countries in five global regions collected intra-abdominal GNB for antimicrobial susceptibility testing using broth microdilution according to the Clinical and Laboratory Standards Institute guidelines. RESULTS: A total of 6156 unique aerobic and facultatively anaerobic GNB were isolated from intra-abdominal infections. Enterobacteriaceae composed 86% of the total isolates. Among the 12 antimicrobial agents tested, the carbapenems and amikacin were the most consistently active against the Enterobacteriaceae. Escherichia coli was the most commonly isolated species (48%), and the susceptibility rate to the quinolones was lowest in Asia/Pacific and Latin America. Extended-spectrum beta-lactamases (ESBLs) were detected phenotypically in 10% of E. coli, 17% of Klebsiella spp. and 22% of Enterobacter spp. worldwide, representing a slight increase over the two previous years. ESBL producers typically had a more antibiotic-resistant profile than non-ESBL producers but were usually susceptible to the carbapenems. CONCLUSIONS: Antimicrobial resistance among GNB isolated from intra-abdominal infections continued to be a problem worldwide in 2004, with the highest rates of resistance overall in the Asia/Pacific region. The carbapenems and amikacin were the most consistently active agents in vitro against Enterobacteriaceae isolated from intra-abdominal infections worldwide.

Abdomen↗

Development of an improved PCR-ICT hybrid assay for direct detection of Legionellae and Legionella pneumophila from cooling tower water specimens.

A novelly improved polymerase chian reaction and immunochromatography test (PCR-ICT) hybrid assay comprising traditional multiplex-nested PCR and ICT, (a lateral-flow device) was developed for direct detection of Legionella bacteria from environmental cooling tower samples. The partial 16S rDNA (specific for Legionella spp.) and dnaJ (specific for Legionella pneumophila) genes from Legionella chromosome were first specifically amplified by multiplex-nested PCR, respectively, followed by detection using ICT strip. Reading of results was based on presence or absence of the two test lines on the strips. Presence of test line 1 indicated existence of Legionella spp. specific 16S rDNA and identified Legionella spp. Presence of test line 2 further indicated existence of dnaJ and thus specifically identified L. pneumophila. In contrast, for non-Legionellae bacteria no test line formation was observed. Results of direct detection of Legionella bacteria and L. pneumophila from water tower specimens by this assay showed 100% sensitivity, and 96.6% and 100% specificity, respectively compared with traditional culture, biochemical and serological identification methods. The PCR-ICT hybrid assay does not require sophisticated equipment and was proved to be practically useful in rapid and direct Legionellae detection from environmental water samples.

Base Sequence↗

Direct and simultaneous identification of Mycobacterium tuberculosis complex (MTBC) and Mycobacterium tuberculosis (MTB) by rapid multiplex nested PCR-ICT assay.

The Mycobacterium tuberculosis (MTB) shows different virulence and host infection range from other members of the M. tuberculosis complex (MTBC). Differential identification of MTB from MTBC is thus important in certain occasions. The currently commercially available molecular assays which use either IS6110 or 16S rDNA fragment as identification targets are mainly designed for identifying MTBC but not for MTB. Comparative genomic DNA analysis has provided valuable information on regions of difference (RD) present in MTB but not in other members of the MTBC. RD9 region is further suggested to be a potential target for differential identification of MTB from MTBC. In this study, using IS6110 and Rv3618 (belong to RD9) as the specific identification targets for MTBC and MTB, respectively, we developed and tested a multiplex nested PCR-ICT (immuno-chromatography test) assay for simultaneously and directly detecting not only MTBC but also MTB from 1500 clinical sputum specimens. The results were compared with traditional culture and biochemical identification results together with patients' clinical assessments. This assay showed a 95.5% sensitivity, 97.9% specificity, 2.1% false positive rate and 4.5% false negative rate towards detection of MTBC, and a 93.0% sensitivity, 99.8% specificity, 0.2% false positive rate and 7.0% false negative rate for detection of MTB. This detection system shows great potential in clinical application.

Chromatography↗

Spontaneous bilateral bacterial empyema in a patient with nephrotic syndrome.

Spontaneous bacterial empyema (SBEM), a rare infectious complication among liver cirrhosis patients, is characterized by infection in the presence of pleural effusion without evidence of pre-existing pneumonia. The prevalence of SBEM in cirrhotic patients with hydrothorax is about 13%. However, it has previously not been reported in medical literature in patients with nephrotic syndrome. The most common microorganism identified is Escherichia coli, followed by Streptococcus species, Enterococcus species, Klebsiella pneumoniae, and Pseudomonas stutzeri. We present a patient with a history of nephrotic syndrome caused by membranous nephropathy, who received steroids and cyclophosphamide. He developed bilateral SBEM due to Aeromonas hydrophila and E. coli, which were isolated from the left- and right-side pleural fluid, respectively. The detailed clinical course, treatment, and outcome are described.

Adult↗

Early empirical glycopeptide therapy for patients with methicillin-resistant Staphylococcus aureus bacteraemia: impact on the outcome.

OBJECTIVES: To evaluate whether appropriate early empirical glycopeptide therapy improves outcomes of patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia. METHODS: We retrospectively collected the data for all adult patients with confirmed MRSA bacteraemia diagnosed and treated at National Taiwan University Hospital during the period 1 April 1997-31 March 2001, and followed their survival up to three years. The main outcome measures were MRSA-related death and all-cause mortality. RESULTS: There were 77 MRSA-related deaths among 162 patients. There was no statistically significant difference in MRSA-related deaths between patients receiving glycopeptides before or within 48 h after blood culture (n = 43) (55%, 18/33, non-septic shock group; 90%, 9/10, septic shock group) or those whose glycopeptide therapy was begun more than 48 h after blood culture (n = 119) (37%, 40/107, non-septic shock group; 83%, 10/12, septic shock group) (P = 0.11 and 1.00, respectively). The outcome measure of all-cause mortality from 30 days to 3 years yields similar results. Multivariate logistic regression analysis and Cox analysis showed that the length of delay (daily increment) between blood culture sampling and start of glycopeptide therapy did not have a statistically significant impact on MRSA-related death or all-cause 30-day mortality after adjusting for the effect of other variables [adjusted odds ratio 0.99, 95% confidence interval (95% CI) 0.88-1.12; adjusted hazard ratio 0.87, 95% CI 0.74-1.02, respectively). CONCLUSIONS: The hypothesis that earlier empirical use of glycopeptide therapy reduces mortality in patients with hospital-acquired MRSA bacteraemia was not supported.

Adolescent↗

Emergence of cefotaxime resistance in Citrobacter freundii causing necrotizing fasciitis and osteomyelitis.

We present a diabetic patient with necrotizing fasciitis caused by Citrobacter freundii associated with an injury from the fish fin. Two isolates recovered six days after cefotaxime treatment had a cefotaxime minimum inhibitory concentration (MIC) of 0.12 and 256 mg/L, respectively, and a cefepime MIC of 0.03 and 0.25 mg/L, respectively. The two isolates both possessed bla(CMY-2) gene. The patient responded unsatisfactorily to cefotaxime and cefepime therapy and surgical debridement but recovered completely after ertapenem treatment for 42 days.

Anti-Bacterial Agents↗

Necrotizing pneumococcal pneumonia in children: the role of pulmonary gangrene.

Little is known about the mechanism of necrotizing pneumonia caused by Streptococcus pneumoniae in children. Pulmonary gangrene secondary to vascular thrombosis was reported in adults with necrotizing pneumococcal pneumonia. We conducted a retrospective study of 15 children with a diagnosis of necrotizing pneumococcal pneumonia at National Taiwan University Hospital to explore its association with pulmonary gangrene, based on evidence from chest computed tomography, serial chest radiographic patterns, and pathologic results. S. pneumoniae serotype 14 was the prevalent pneumococcal serotype. Overall, 63.6% of isolates were not susceptible to penicillin. One child with pneumonia caused by S. pneumoniae serotype 3 complicated by hemolytic uremic syndrome had a rapidly fatal course. An autopsy in this patient documented lung necrosis and pulmonary gangrene. Radiographic follow-up was performed during the clinical course in 9 patients, and showed no evidence of pulmonary gangrene. Four children had no radiographic follow-up. The relationship between pulmonary gangrene and necrotizing pneumonia was unclear in the remaining one. In conclusion, necrotizing pneumococcal pneumonia may be infrequently associated with pulmonary gangrene in children.

Child↗