Invasive infection caused by Penicillium marneffei: an emerging pathogen in Taiwan.
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Biomedical subjects
Publications and source records attributed to K T Luh.
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The in-vitro susceptibilities of 13 antimicrobial agents were determined for 207 isolates of viridans group streptococci recovered from patients with significant infections in Taiwan during 1995 and 1997. Variable degrees of susceptibility existed among nine species. High-level penicillin resistance (MIC > or = 4.0 mg/L) was found most frequently in Streptococcus oralis (35%), followed by Streptococcus mitis (20%) and Streptococcus salivarius (8%). However, S. salivarius showed the lowest rate of susceptibility to penicillin (50%). Macrolide resistance also occurred most frequently in S. oralis isolates (55%) but in none of Streptococcus mutans. Penicillin and macrolides tended to be less active against isolates recovered from non-invasive sites than against those isolated from invasive sites. Imipenem was the most active beta-lactam against penicillin-resistant isolates. Ofloxacin, vancomycin and teicoplanin showed good in-vitro activity against all isolates, with MIC90s of 2, 1 and 0.25 mg/L, respectively. None of these isolates displayed high-level resistance to gentamicin and most isolates were susceptible to chloramphenicol. These results indicate the species-related variability of susceptibility, especially to penicillin, macrolides and tetracycline. In addition to S. mitis, S. oralis also displayed high rates of resistance to penicillin and macrolides. The difference in susceptibilities between species of viridans streptococci indicates the importance of accurate identification and the need for continuing surveillance of antimicrobial resistance.
The clinical courses of 35 tuberculous empyema patients were investigated retrospectively from November 1990 through November 1995. Most patients had nonspecific symptoms and signs but with far-advanced pulmonary parenchymal lesions in their chest roentgenographs. The effusions showed neutrophilic leukocytosis with a 60% positive culture rate for Mycobacterium tuberculosis. Multidrug resistant strains were found in 7 out of 18 cultures. All patients received chemotherapy and eight of them underwent additional surgical management. Twenty-two (62.9%) patients had been treated successfully and one patient is still under treatment. The remaining 12 patients either died during treatment or defaulted; and four (11.4%) of them had died of tuberculosis. We conclude that the treatment outcome of tuberculous empyema is less satisfactory than that of pulmonary tuberculosis, however, modern multidrug chemotherapy with repeated drainage and opportune surgical interventions could be in prospect of successful treatment of tuberculous empyema.
From 7 to 24 March 1997, four patients developed Pseudomonas fluorescens bacteremia at the hospital; one on the oncology ward and the other three in the chemotherapy room. These patients all had underlying malignancies and had the Port-A-Cath (Smiths Industries Medical Systems, Deltec, Inc., St. Paul, Minn.) implants. Three patients had primary bacteremia, and one had Port-A-Cath-related infection. None of these patients had received a blood transfusion before the episodes of bacteremia. All patients recovered: two received antimicrobial agents with in vitro activity against the isolates, and the other two did not have any antibiotic treatment. A total of eight blood isolates were recovered from these patients during the febrile episodes that occurred several minutes after the infusion of chemotherapeutic agents via the Port-A-Cath. These isolates were initially identified as P. fluorescens or Pseudomonas putida (four), Burkholderia (Ralstonia) pickettii (three), and a non-glucose-fermenting gram-negative bacillus (one) by routine biochemical methods and the Vitek GNI card. These isolates were later identified as P. fluorescens on the basis of the characteristic cellular fatty acid chromatogram and the results of supplemental biochemical tests. The identification of identical antibiotypes by the E test and the random amplified polymorphic DNA patterns generated by arbitrarily primed PCR of the isolates showed that the outbreak was caused by a single clone of P. fluorescens. Surveillance cultures of the possibly contaminated infusion fluids and disinfectants, which were performed 7 days after recognition of the last infected patient, failed to isolate P. fluorescens. This report of a small outbreak caused by P. fluorescens suggests that timely, accurate identification of unusual nosocomial pathogens is crucial for early initiation of an epidemiological investigation and timely control of an outbreak.
Long-term colonization of various body sites with a multidrug-resistant Pseudomonas aeruginosa clone (resistant to piperacillin, cefoperazone, ceftazidime, aztreonam, imipenem, cefepime, cefpirome, ofloxacin, ciprofloxacin, minocycline, and aminoglycosides) with subsequent severe infections in burn patients has not been reported previously. Thirty-nine isolates of multidrug-resistant P. aeruginosa (resistant to ceftazidime and at least three of the agents listed above) recovered from various clinical samples from three patients in an intensive care burn unit from April 1997 to May 1997 and seven preserved isolates recovered from six patients in other medical wards at National Taiwan University Hospital from April 1996 to May 1997 were studied for their epidemiological relatedness. The epidemic could be attributed to a multidrug-resistant P. aeruginosa clone belonging to serogroup O:F (serogroup O:4) by means of antimicrobial susceptibility testing, O serogrouping, and analysis of the randomly amplified polymorphic DNA patterns generated by arbitrarily primed PCR of the isolates. The epidemic strain persisted in the three patients for weeks to months; in the meantime, these patients had received multiple antimicrobial agents for the management of intervening episodes of invasive infections (bacteremia, ventilator-associated pneumonia, and/or catheter-related sepsis) caused by this strain, as well as concomitant infections due to other organisms. The strain had been isolated only once previously, from a burn patient who was on the unit in December 1996. The present report, describing a small outbreak due to P. aeruginosa, documents the fact that a single clone of multidrug-resistant P. aeruginosa can cause long-term persistence in different body sites of burn patients and that the colonization can subsequently result in various severe infections.
We describe herein a recurrent catheter-related (Port-A-Cath; Smiths Industries Medical Systems [SIMS] Deltec, Inc., St. Paul, Minn.) infection caused by multidrug-resistant Mycobacterium chelonae with two colonial morphotypes in a 53-year-old woman with gastric adenocarcinoma. Four isolates recovered from this patient within a 3-month period were found to belong to a single clone on the basis of the isolates' identical antibiotypes as determined by the E test and their identical random amplified polymorphic DNA patterns.
Tracheal botryomycosis has never been reported in the literature. A 68 year old man presented with progressive dyspnoea and an exophytic mass below the vocal cords was found by bronchoscopy. Pathological study of the mass showed tracheal botryomycosis probably associated with Peptostreptococcus spp infection. The patient was given intravenous penicillin for six weeks. Tracheal obstruction necessitated tracheal resection and the surgical specimen revealed typical findings of tracheopathia osteochondroplastica without residual lesions of botryomycosis.
BACKGROUND: The clinical value of colour Doppler ultrasound and amplitude ultrasound angiography in the diagnosis and follow up of pulmonary arteriovenous malformations (PAVM) was investigated. METHODS: Six consecutive patients suspected by clinical appearance and abnormal chest radiographic findings of having PAVM were included in the study. Ultrasonography was performed first by real time grey scale imaging then by colour Doppler imaging and amplitude ultrasound angiography in a random order. All were later proved by angiography to have PAVM. RESULTS: The ultrasound study was successfully performed in all six patients. A total of eight lesions was detected. The real time grey scale image of PAVM revealed well defined hypoechoic subpleural nodules with strong posterior acoustic enhancement. Colour Doppler ultrasound of PAVM showed turbulent flow, manifest as an area of intense colour with high and mixed velocities (reticulated or mosaiclike pattern). Anatomical continuity was demonstrated in some PAVM. Amplitude ultrasound angiography can delineate a tangled vascular structure with a clear vessel wall and anatomical continuity as well as conventional angiography. Spectral wave analysis showed a relatively low impedance flow presenting with high peak systolic velocity (mean 44.4 cm/s) and relatively high diastolic velocity (mean 19.3 cm/s). The mean pulsatility index (PI) and resistive index (RI) were 1.80 and 0.49, respectively. In two patients who received embolotherapy the colour Doppler ultrasound scan obtained after the procedure showed that the previous focal areas of colour flow signals disappeared or diminished in size. This was compatible with the decrease in, or absence of, blood flow demonstrated by angiography after embolotherapy. CONCLUSIONS: Combined colour Doppler ultrasound and amplitude ultrasound angiography are useful non-invasive techniques for diagnosis PAVM and provide an alternative approach to angiography in evaluating the efficacy of embolotherapy.
Epidermal growth factor (EGF) stimulates the Na(+)-H+ exchanger, leading to enhanced cell proliferation. In human pleural mesothelial cells (PMCs), the intracellular signaling mechanism mediating the EGF-induced stimulation of the Na(+)-H+ exchanger has not yet been identified. Using a pH-sensitive fluorescent probe, 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein, to measure changes in intracellular pH (pHi), we found that 1) EGF and 12-O-tetradecanoylphorbol 13-acetate (TPA; a phorbol ester) both stimulate the ethylisopropyl amiloride-sensitive Na(+)-H+ exchanger; 2) TPA-induced alkalosis can be blocked by protein kinase C (PKC) inhibitors (chelerythrine and staurosporine) or by PKC down-regulation, indicating that PKC activation is involved in the stimulation of the Na(+)-H+ exchanger. However, TPA-induced alkalosis is not blocked by tyrosine kinase inhibitors; and 3) the stimulatory effect of EGF on the Na(+)-H+ exchanger acts via stimulation of tyrosine kinase-receptor activity because it is inhibited by tyrosine kinase inhibitors (genistein, lavendustin A, and herbimycin A). It also involves PKC activation because EGF-induced alkalosis was blocked by PKC inhibitors. These results suggest that PKC activation is one of the downstream signals for EGF-induced activation of the Na(+)-H+ exchanger in primary cultures of human pleural mesothelial cells.
The expression of mucins is important for tumor invasiveness and metastasis. In our previous report (Am. J. Respir. Crit. Care Med. 1997; 155:1419-1427), non-small cell lung cancers bearing sialomucin expression tended to relapse earlier than those without sialomucin. However, it remained unclear whether the expression of sialomucin in lung cancer is caused by an abnormal glycosylation process or by the expression of a specific mucin gene product. To address this problem, we established a modified quantitative competitive polymerase chain reaction (QC-PCR) analysis. RNA internal standards of MUC1, MUC2, and MUC5AC non-tandem repeat sequences were constructed, and known copy numbers of mucin RNA internal standards were introduced into reverse transcription-polymerase chain reactions (RT-PCR) for each mucin gene in order to compete with native mucin gene RNA during the reaction. The RNA of Gbeta-like gene (a housekeeping gene) was used as internal control for the RNA analysis. Twenty-five lung cancer tissues (13 adenocarcinomas and 12 squamous cell carcinomas) were used for analysis. Mann-Whitney rank sum test was applied to compare the expression amounts of different mucin genes in tissues. The results revealed that adenocarcinoma expressed higher amounts of MUC5AC gene than did squamous cell carcinoma (P = 0.03). The expression amount of MUC5AC correlated positively with the expression status of sialomucin (P = 0.012). Further studies are anticipated to elucidate the underlying mechanism contributing to this phenomenon.
Long-term preservation of 40 isolates of Helicobacter pylori was investigated with five storage media (brucella broth with 17% glycerol, brucella broth with 17% glycerol and 2% fetal calf serum [FCS], brucella broth with 17% glycerol and 10% FCS, brucella broth with 17% glycerol and 2% horse blood, and 10% mucin) at -70 degrees C for 4, 6 and 9 months. In addition to glycerol, FCS or horse blood in the storage media is necessary for survival of H. pylori. Storage of H. pylori isolates at -70 degrees C in 10% mucin is a simple and effective preservation procedure.
Thirty five patients with tuberculous peritonitis were studied retrospectively. Tuberculous peritonitis was defined as the isolation of Mycobacterium tuberculosis from ascites or dialysate, and/or caseating granuloma/acid-fast bacilli from peritoneal biopsy specimens from patients with pulmonary tuberculosis or a response to treatment for tuberculosis. Among the patients studied, nine with cirrhosis of the liver; seven with diabetes mellitus and six with end-stage renal disease, of whom four had undergone continuous ambulatory peritoneal dialysis. The most frequent signs of tuberculous peritonitis included ascites, fever and anemia. Ascites was found in 31 patients (89%). Abnormal findings on chest radiographs were found in 26 patients (74%), of whom 22 patients (63%) had pleural effusion and five had miliary lung lesions. Seven out of 35 patients were found to have positive culture of sputum or pleural effusion for M. tuberculosis. Two patients were found to have concomitant tuberculous peritonitis and enteritis. Multiple organ involvement was found in eight patients. Eleven patients (31%) died: eight were older than 60 years; six had cirrhosis of the liver and nine were diagnosed post-mortemly. In Taiwan, tuberculous peritonitis should be considered in patients with abnormality of chest radiography and nonresolving peritonitis.
Capnocytophaga has been recognized as an opportunistic pathogen causing systemic infections in immunocompromised individuals with granulocytopenia and oral ulceration. Treatment of Capnocytophaga infection is often empiric. We retrospectively analyzed the clinical features of all patients with Capnocytophaga bacteremia seen at the National Taiwan University Hospital between January 1981 and December 1996 and the antimicrobial susceptibility of the isolates recovered from these patients. All the patients had underlying diseases, namely neoplastic disease (9 patients), hyperthyroidism (1), and bronchiectasis and tetralogy of Fallot (1). The clinical features of these patients were primary bacteremia (10) and pneumonia (1). Nine patients had nosocomial bacteremia and 10 patients had monomicrobial bacteremia. None had septic shock. All the patients responded well to appropriate antimicrobial therapy and survived. All isolates were susceptible to amoxicillin-clavulanate, imipenem, ciprofloxacin, erythromycin, clindamycin, tetracycline, and chloramphenicol but resistant to aminoglycosides and sulfamethoxazole-trimethoprim. The susceptibilities to penicillin, ampicillin, piperacillin, cephalosporins, and aztreonam were variable. Capnocytophaga bacteremia should be included in the differential diagnosis of febrile neutropenia in immunocompromised patients, especially in the presence of oral mucositis and ulceration.
Pulmonary arteriovenous malformation (PAVM) is an uncommon but not rare disease. It is very often associated with hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease, OWRD). Both conditions may be readily diagnosed at the bedside when careful attention is given to clues from history taking and physical examination. Sometimes the clinical features may be neglected, delaying the diagnosis. The natural history of this disease is still incompletely understood because of the paucity of cases. This retrospective study was undertaken to evaluate the clinical manifestations and treatment options in patients with documented PAVM at the National Taiwan University Hospital between 1985 and 1997. Ten patients (4 men, 6 women) of documented PAVM were evaluated. Mean age at diagnosis was 37.8 years (range 22-63). Presenting symptoms included dyspnea on exertion, characteristics of OWRD, and major neurologic events. Six episodes of brain abscess occurred in three patients. The predominant location of PAVMs was the lower lobe. Solitary PAVM was more frequent in our patients (5/6) with OWRD than in other reports. The therapeutic options were: surgical resection (3 patients), embolotherapy (4), and no treatment (4). One patient, who refused treatment at first, developed a brain abscess later. There was no documented recurrence or growth of new PAVMs in patients who underwent surgical resection. Embolotherapy failed in one patient; no recanalization was found in the remaining patients. In conclusion, the diagnosis of PAVM may be subtle, but careful attention to historic clues and physical findings may lead to early diagnosis. Appropriate treatment is mandatory and may prevent the severe complications of PAVM. The debate about the preferred treatment seems likely to continue until more is known about the natural history of this disease.
We evaluated the performance of an automatic polymerase chain reaction (PCR) detection system for identification of Mycobacterium tuberculosis in respiratory specimens. Six hundred and two respiratory specimens, including 557 sputa and 45 bronchial washing samples, were analyzed using the COBAS AMPLICOR Mycobacterium tuberculosis (MTB) test. The results were compared with those obtained from acid-fast microscopy, conventional culture, and clinical history. In cases of discrepancy between the results of the COBAS AMPLICOR MTB test and culture, the medical history of the patient was reviewed, the COBAS AMPLICOR MTB test was repeated, and the gene encoding M. tuberculosis superoxide dismutase was screened using PCR (SOD-PCR). Fourteen samples were excluded because the internal control test result was negative. Of 57 specimens that were culture positive for Mycobacterium species, 40 appeared to have growth of M. tuberculosis and 21 were smear positive for acid-fast bacteria. The sensitivity, specificity, and positive and negative predictive values for the COBAS AMPLICOR MTB test evaluated at our laboratory were 85.0% (34/40), 99.3% (544/548), 89.5% (34/38), and 98.9% (544/550), respectively. Three specimens that were culture positive for M. tuberculosis but negative by COBAS AMPLICOR MTB test were positive when rechecked by both COBAS AMPLICOR MTB test and SOD-PCR. Among the four specimens with positive reactions on both COBAS AMPLICOR MTB test and SOD-PCR that were culture negative, two were from patients who had been receiving antituberculosis treatment, one was from a patient who had been treated for tuberculosis for 1 year, and the other was from a patient who died of sepsis with adult respiratory distress syndrome. In more than 70% of smear-negative and culture-positive specimens and 86.4% of smear-positive specimens, M. tuberculosis was identified by the COBAS AMPLICOR MTB test within 10 hours after receipt of the specimens. Our data show that the COBAS AMPLICOR MTB test provides rapid and accurate detection of M. tuberculosis in respiratory specimens.
Pulmonary sequestration, an uncommon congenital anomaly, is traditionally best diagnosed using arteriography; however, this is invasive and not without risk of morbidity and mortality. We report two patients with pulmonary sequestration diagnosed using magnetic imaging techniques. The first was a 22-year-old woman and the second a 17-year-old boy, both of whom presented with symptoms of cough and exertional dyspnea. Pulmonary sequestration was suspected from their chest radiographs. Magnetic resonance imaging and magnetic resonance angiography clearly demonstrated the aberrant artery arising from the aorta in a single noninvasive examination that did not require the use of contrast medium. We recommend magnetic resonance imaging as a safe, efficient, and noninvasive modality for the diagnosis of pulmonary sequestration.
Standard short-course chemotherapy including isoniazid, rifampicin, pyrazinamide, and ethambutol has been the recommended treatment for tuberculosis in Taiwan since November 1990. The effectiveness of this treatment was evaluated retrospectively in 108 patients with isolates resistant to isoniazid alone and 115 patients with drug-susceptible pulmonary tuberculosis diagnosed and treated at the Taiwan Provincial Chronic Disease Control Bureau from November 1990 through December 1995. The success rate of treatment was 94.4% in patients with isoniazid-resistant Mycobacterium tuberculosis strains, which was not significantly different from the 97.4% rate in patients with susceptible strains. Of the patients treated successfully, no bacteriologic relapse was found in 97 patients with isoniazid-resistant strains or 103 patients with drug-susceptible strains 12 months after the end of chemotherapy. No significant advantage in treatment outcome was found in patients infected with isoniazid-resistant strains who received chemotherapy for more than 6 months (successful treatment rate, 95.0% vs 92.8%), but the failure rate was higher in patients with a previous history of antituberculosis therapy (17.6% vs 3.3%). We conclude that short-course chemotherapy is effective for isoniazid-resistant pulmonary tuberculosis and that there is no significant difference in treatment outcome between patients with or without isoniazid-resistant disease.