Multidrug resistance in clinical isolates of Stenotrophomonas maltophilia: roles of integrons, efflux pumps, phosphoglucomutase (SpgM), and melanin and biofilm formation.

Integrons, efflux pumps, phosphoglucomutase (SpgM), and melanin and biofilm formation were investigated in 40 multidrug-resistant (MDR) and 30 non-MDR Stenotrophomonas maltophilia isolates recovered from patients treated at National Taiwan University Hospital (Taipei, Taiwan). Class 1 integrons were clearly associated with multidrug resistance. Sequencing data revealed that aminoglycoside-modifying genes occurred most frequently in the integron and disclosed a new bla(IMP-8)/aac6-II/aadA5 gene cassette. Semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) was performed to assess the expression of Sme efflux pumps and SpgM in S. maltophilia. MDR isolates exhibited hyperexpression of SmeABC, and SmeDEF and SpgM were more frequently found in MDR isolates than non-MDR isolates. In addition, the ability of MDR isolates to form melanin-like pigment and biofilm was also greater than that of the non-MDR isolates. The SmeABC or SmeDEF pump was shown to be associated with resistance to all agents tested. The presence of an integron as well as production of pigment and biofilm was also responsible for resistance against eight, six and six of the tested agents, respectively. High SpgM expression was associated with resistance to only three of the tested agents. These findings define the important roles of integrons, efflux pumps, and melanin-like pigment and biofilm formation in the multidrug resistance of S. maltophilia. MDR isolates possessed more resistance mechanisms than susceptible strains.

Disseminated Cryptococcus neoformans var. grubii infections in intensive care units.

A retrospective study of clinical characteristics, outcome and prognostic factors of patients with cryptococcosis was undertaken in intensive care units (ICUs) of a medical centre for the period 2000-2005. Twenty-six patients with Cryptococcus neoformans var. grubii infection were identified (16 males, median age 58 years). The most frequent underlying diseases were liver cirrhosis (38.5%), diabetes mellitus (26.9%) and HIV infection (19.2%). The most frequently identified sites of infection were blood (61.5%), cerebrospinal fluid (38.5%) and airways (34.6%). The mean Acute Physiologic and Chronic Health Evaluation II score at ICU admission was 22.46. The ICU mortality rate in these patients was 73.1% (19/26) and there were a further two mortalities recorded after discharge from ICU, reaching a total mortality rate of 80.8% (21/26). Patients with ICU survival >2 weeks had lower rates of HIV infection (P=0.004), less use of inotropic agents during ICU stay (P<0.001) and lower white blood cell counts (P=0.01). After adjusting for clinical variables in the multivariate Cox regression model, diabetes and cryptococcal infection after ICU admission were independent predictors of good long-term prognosis (P=0.015) and HIV infectious status was associated with poor outcome (P=0.012).

Microbiological characteristics of clinical isolates of Cryptococcus neoformans in Taiwan: serotypes, mating types, molecular types, virulence factors, and antifungal susceptibility.

This study investigated the microbiological characteristics of 100 clinical isolates of Cryptococcus neoformans species complex, including serotypes, mating types, molecular types, antifungal susceptibility and virulence. The isolates were collected at National Taiwan University Hospital from 1999 to 2004. Eight isolates of C. neoformans from pigeon droppings were also evaluated. Among these isolates, 99 were C. neoformans var. grubii serotype A and one was C. neoformans var. gattii serotype B. All of these isolates were alpha mating types. PCR fingerprinting, generated by primers M13 and (GACA)(4), and URA5 gene restriction fragment length polymorphism analysis revealed that C. neoformans var. grubii isolates belonged to the VNI (98 isolates) and the VNII (one isolate) types, and the single C. neoformans var. gattii was VGI type. The similar profiles of clinical and environmental isolates suggest that patients might acquire these yeasts from the environment. The MIC(90) for fluconazole, itraconazole, 5-flucytosine, voriconazole and amphotericin B against all C. neoformans isolates were 8, 0.5, 4, 0.125 and 0.5 mg/L, respectively. All clinical isolates produced urease, phospholipase, capsule and melanin, but these activities varied with individual isolates. Analysis of six clinical and two environmental isolates with various levels of phospholipase activity indicated a correlation between phospholipase activity and the ability to adhere to the lung epithelial cell line, A549. The extent of cell damage, as indicated by lactate dehydrogenase release, also paralleled the phospholipase activity of these isolates. In addition, production of melanin contributed significant protection against amphotericin B killing of the isolates tested.

Adrenal insufficiency in critically ill emergency department patients: a Taiwan preliminary study.

OBJECTIVE: Unrecognized adrenal insufficiency can have serious consequences in critically ill emergency department (ED) patients. This prospective pilot study of adrenal function in patients with severe illness was undertaken to determine the prevalence of adrenal dysfunction and any relation to prior herbal drug use. METHODS: In a high-volume urban tertiary care ED, adult patients with sepsis or acute myocardial infarction (AMI) were eligible for the study. Over a two-month period, a convenience sample was enrolled by the authors on arrival to the ED. Inclusion criteria were systemic inflammatory response syndrome (SIRS) criteria plus evidence of at least one organ dysfunction or cardiac marker plus electrocardiogram-proven AMI. Exclusion criteria included known corticosteroid use. Serum cortisol was measured on arrival and for those patients with a level of <15 microg/dL (<414 nmol/L), an adrenocorticotropic hormone (ACTH) stimulation test was performed. RESULTS: Of the 30 enrolled patients, 23 (77%) were suffering from severe sepsis and the other seven (23%) had an AMI. Thirteen of the 30 patients (43%; 95% CI = 25% to 65%) had serum cortisol levels of <15 microg/dL, consistent with adrenal insufficiency, nine with severe sepsis and four with an AMI. Eight (62%; 95% CI = 32% to 86%) of the 13 patients with low cortisol levels reported using herbal medications, while only two (12%; 95% CI = 1% to 36%) of the 17 with normal cortisol levels reported taking herb drugs (p = 0.01). Only two (15%; 95% CI = 2% to 45%) of the patients with low cortisol levels failed their corticotropin stimulation test, suggestive of true adrenocortical insufficiency. Both reported using herbal preparations. CONCLUSIONS: These results indicate that adrenal dysfunction is common among a group of critically ill patients seen in this Taiwanese ED. Moreover, the use of herbal drugs was high in the patients with low serum cortisols. Further studies are required to both confirm these findings and clarify whether a number of herbal medications contain corticosteroids.

Risk of immediate effects from F(ab)2 bivalent antivenin in Taiwan.

OBJECTIVE: To evaluate the incidence of immediate adverse effects from equine fragment antigen binding F(ab)2 bivalent antivenin produced by the National Institute of Preventive Medicine (NIPM) in Taiwan. METHODS: A retrospective chart review of patients presenting to a 600-bed general hospital over a 3-year period with snakebite who were treated with NIPM antivenin. RESULTS: A total of 130 snakebite victims presented to the emergency department over the study period, and 159 vials of antivenin were given. One hundred two patients (78.5%; 95% CI: 70, 85) received only hemorrhagic bivalent antivenin, 2 (1.5%; 95% CI: 0, 5) received only neurotoxic bivalent antivenin, and the remaining 26 (20.0%; 95% CI: 13, 28) received both kinds of bivalent antivenin. Three received a second vial of hemorrhagic antivenin because of progression of symptoms. Forty-two patients (32.3%; 95% CI: 24, 41) had positive skin tests, but following pretreatment with diphenhydramine and hydrocortisone, only 1 patient developed a skin rash thought to be related to antivenin. No patient developed an anaphylactic reaction. CONCLUSIONS: The use of NIPM F(ab)2 antivenin in snakebite victims in Taiwan has a very low risk of acute adverse reactions.

Differences of disease characteristics between genders in emergency department elderly of a community hospital in Taiwan.

BACKGROUND: The purpose of this study was to catalog the chief complaints and diagnoses of elderly patients visiting to a Taiwanese emergency department (ED), and to compare gender differences. METHODS: ED computer log data of patients 65 years and older, who visited the ED from July 1995 to June 1996, were retrospectively reviewed. The computer log data for each patient was entered prospectively by the doctor providing the ED care. All patient data were separated by gender, and then subdivided into trauma and non-trauma groups for analysis. RESULTS: There were 8038 elderly patients treated during the study period. The most common male chief complaint was dyspnea, and for females, it was abdominal pain, followed by injuries for both genders. Falls were the most common mechanism of injury for both genders, but they were more common among females (63.2% vs. 46.1%, p < 0.001). Motorbike accidents, however, were 3 times as frequent among males (16.05% vs. 5.45%, p < 0.001). Males presented most commonly with COPD (12.2%), compared to only 4.16% for females (p < 0.001), with urinary retention the second most common diagnosis (5.04% vs. 0.72%, p < 0.001). Females suffered a greater number of urinary tract infections (5.42% vs. 2.03%, p < 0.001), presentations for renal failure (2.98% vs. 1.56% p < 0.001), and diabetes-associated problems (4.58% vs. 2.48%, p < 0.001). CONCLUSION: Elderly females presented to the ED more frequently with urinary tract and diabetic problems; while their male counterparts presented with complications of COPD, urinary retention, and motorbike accidents.

Treatment of poisonous snakebites in northern Taiwan.

PURPOSE: We evaluated the epidemiology and outcomes of snakebites in northern Taiwan, and the effect of local antivenom injection to speed neutralization and reduce the spread of venom. METHODS: We retrospectively reviewed the medical records of 130 venomous snakebite patients treated in a general hospital in northern Taiwan during a 3-year period (1991-1994). Patients received either combined local and intravenous injection of antivenom or intravenous administration only, according to the physicians' decision. The species of snake involved, time of bite, and outcome of the patient were recorded. The effect sof local and systemic antivenom administration were analyzed using the duration of emergency department (ED) stay among patients discharged from the ED with medical approval as a treatment index. RESULTS: Most (76.1%) venomous snakebites were attributed to the green habu (68 patients) and the Taiwan habu (31 patients). All bites were to the extremities: 74 (57%) to the feet and 56 (43%) to the hands or arms. Most bites (n = 70, 53.9%) occurred between 2 PM and 9 PM. The peak months for snakebites were June through October (n = 84, 64.6%). Eighteen patients (13.8%) were admitted for further treatment after being cared for in the ED. The other 112 patients were discharged from the ED (86.2%), although three of these were admitted later because of infection. No patients died, but eight developed wound infections. Of the 93 patients discharged from the ED with medical approval, 26 (28.0%) received local injection plus systemic administration of antivenom. The duration of ED stay did not differ significantly between patients with local plus systemic administration and those who received systemic administration alone (23.7 +/- 19.5 hours vs 27.0 +/- 12.5 hours, p = 0.19). CONCLUSIONS: Most snakebites in northern Taiwan were due to habus and caused mild symptoms. Local antivenom injection plus intravenous administration of antivenom had no benefit over intravenous administration alone.

Clinical presentations of elderly patients at emergency departments: a comparison between a medical center and a community hospital.

BACKGROUND: The utilization of emergency services is expected to increase in parallel with an increase of the elderly population. This article compares the elderly patient Emergency Department (ED) utilization at a 3500-bed medical center with that of a 600-bed community hospital serviced by the same group of emergency physicians. METHODS: We retrospectively reviewed all patients over 64 years old who presented to Linkou Chang Gung Memorial Hospital (CGMH) and Keelung CGMH between July 1, 1995 and June 30, 1996 by using the 2 ED's real-time computer logs. Data comparisons included age, gender, mode of arrival, arriving source, triage category, chief complaint, impression, and final disposition. RESULTS: There were 18,285 patients in the Linkou ED and 8038 in Keelung. Significant differences in arrival mode, arriving source, triage category, disease pattern, and final disposition were observed between the Linkou and Keelung CGMH EDs. CONCLUSION: Significant differences reflected the different roles between the Linkou and Keelung CGMH EDs. Hospital EDs should be prepared to adapt to meet the needs of the elderly based on their roles in the medical care system, at the elderly population grows in the 21st century.

Diverse manifestations of oral methylene chloride poisoning: report of 6 cases.

OBJECTIVE: Methylene chloride is a solvent used in domestic and industrial preparations, such as paint removers and degreasing agents. Although it is considered of low toxicity, acute toxic manifestations have been reported following inhalation of methylene chloride, mainly from working in an enclosed environment. Oral ingestion of methylene chloride, however, remains rare and its consequences are less clearly understood. CASE REPORTS: The various clinical manifestations of 6 patients with oral ingestion of methylene chloride are reported. Central nervous system depression, tachypnea, and corrosive gastrointestinal injury were the most common presentations following ingestion. An elevated carboxyhemoglobin level was documented in only 2 patients (35% and 8.4% carboxyhemoglobin, respectively). Due to a frequent misleading history of "chloroform" ingestion and unawareness of probable carboxyhemoglobin production in these patients, carboxyhemoglobin was not routinely measured. Renal failure, hepatic failure, and acute pancreatitis occurred in the 2 most severe cases of methylene chloride ingestion. CONCLUSIONS: Ingestion of methylene chloride can result in diverse manifestations, including a high carboxyhemoglobin level. Corrosive gastrointestinal injury is common in oral poisoning and needs further therapeutic consideration. A high index of suspicion and appropriate laboratory studies are needed in those patients who allegedly ingest "chloroform" but do not present the incriminating solvent to their treating physicians. The presence of an elevated carboxyhemoglobin level suggests the diagnosis of methylene chloride poisoning. Symptomatic and supportive measures remain the mainstay in the treatment of patients with oral methylene chloride poisoning.

Rates and causes of emergency department revisits within 72 hours.

The purpose of this study was to determine the rates and causes of revisits to the emergency department (ED) of a 3,500-bed referral hospital, to identify areas for improvement, and to generate baseline data for the development of a computerized, automatic monthly audit system. We identified all patients returning within 72 hours of their initial ED visits, from 1 July 1995 to 30 June 1997, and monthly revisit rates were calculated. To determine the reasons for revisits, two independent reviewers examined the charts of revisit cases from 1 July 1996 to 30 June 1997. A one-in-three sampling method was used to select charts. A total of 485 revisit charts were reviewed. The monthly revisit rates ranged from 1.32% to 2.38%, with no particular seasonal or event-specific pattern. Most revisits were attributed to disease factors (79.0%). Those felt to be medical errors only accounted for 7.8% of the revisits but led to a higher hospital admission rate (73.7%) subsequently. By contrast, the overall hospital admission rates for revisit patients (36.5%) and all ED patients (36.2%) were similar. We suggest setting baseline monthly ED revisit rates at 2% for future computer-programmed audit filters. While this study indicates that most revisits are disease-related, further prospective studies are needed to evaluate the most common and serious causes of revisits to see if improvements can be made.

Risk of transient hyperammonemic encephalopathy in cancer patients who received continuous infusion of 5-fluorouracil with the complication of dehydration and infection.

From 1986 to 1998, 29 cancer patients who had 32 episodes of transient hyperammonemic encephalopathy related to continuous infusion of 5-fluorouracil (5-FU) were identified. None of the patients had decompensated liver disease. Onset of hyperammonemic encephalopathy varied from 0.5 to 5 days (mean: 2.6 +/- 1.3 days) after the initiation of chemotherapy. Plasma ammonium level ranged from 248 to 2387 microg% (mean: 626 +/- 431 microg%). Among the 32 episodes, 26 (81%) had various degrees of azotemia, 18 (56%) occurred during bacterial infections and 14 (44%) without infection occurred during periods of dehydration. Higher plasma ammonium levels and more rapid onset of hyperammonemia were seen in 18 patients with bacterial infections (p=0.003 and 0.0006, respectively) and in nine patients receiving high daily doses (2600 or 1800 mg/m2) of 5-FU (p=0.0001 and < 0.0001, respectively). In 25 out of 32 episodes (78%), plasma ammonium levels and mental status returned to normal within 2 days after adequate management. In conclusion, hyperammonemic encephalopathy can occur in patients receiving continuous infusion of 5-FU. Azotemia, body fluid insufficiency and bacterial infections were frequently found in these patients. It is therefore important to recognize this condition in patients receiving continuous infusion of 5-FU.

Compliance with the law and appropriate medical standards during interhospital transfers.

Interhospital transfer patients constitute a significant proportion of medical center emergency department (ED) patients in Taiwan. Many such transfers are poorly planned and put the patient at risk. We wished to evaluate the safety and compliance with the Taiwan Medical Law among patients transferred to the Linkou Chang Gung Memorial Hospital ED from other health care centers. We performed a prospective, cross-sectional, observational study on 1,056 patients transferred from August 15 to September 30, 1997. Of these patients, 357 were critically ill or injured and only 160 received adequate pretransfer stabilization. The major omissions included: 1) failure to intubate in 121 (55%) of the 220 patients in severe respiratory distress or unprotected patent airways; 2) no intravenous line in 74 (20.7%) of the 357; and 3) inadequate IV lines in 36 (63.2%) of the 57 severely hypotensive patients. Overall, 894 patients were sent with transfer notes, but few indicated whether the referral was to the ED or outpatient department. This added an unnecessary burden for patients with stable longstanding problems who claimed they had been referred to the ED. While the majority of patients (49.4%) were transferred at the request of physicians for further treatment, 28% of the critically ill patients were transferred because of family requests. Physicians accompanied these patients only on seven occasions and nurses on 84 occasions. Despite the 1993 Department of Health policy of pretransfer phone contact with the receiving hospital for critically ill patients, such contact occurred only 10.6% of the time. While the Taiwan emergency medical system, Emergency Medicine, and Critical Care Medicine are all in their developmental stages, a medical and legal noncompliance rate of above 55% for critically ill transfer patients is unacceptably high. The appropriate medical societies and the Department of Health should work in concert to upgrade existing transfer practices.

Heterogeneity of resistance elements in clinical isolates of enterococci with high-level gentamicin resistance.

High-level resistance (minimum inhibitory concentration, MIC > 1,000 micrograms/ml) to gentamicin (HLGR) in enterococci is common in Taiwan. In this study, we investigated the distribution of gentamicin resistance elements in enterococci isolated at National Taiwan University Hospital in a 1-year period, and also examined the transfer and the genetic variability of the resistance elements of different isolates. Among 109 isolates tested, 43 (39%) HLGR isolates were identified. HLGR was most common in Enterococcus faecium isolates (7/15, 47%), followed by Enterococcus faecalis (34/80, 43%), Enterococcus avium (1/5, 20%), and Enterococcus casseliflavus (1/9, 11%). To understand the mechanism of resistance transfer, four isolates of E. faecalis and five isolates of E. faecium showing HLGR were studied. Transfer of resistance markers to a plasmid-free recipient strain of E. faecalis JH2-7 was observed, with transfer frequencies ranging from 10(-2) to 10(-8). All of the transconjugants contained plasmids, with sizes ranging from 45 kb to larger than 70 kb. At least three plasmid patterns were observed on digestion with HaeIII. Hybridization with a probe specific for the aac6'aph2" gentamicin resistance gene confirmed that all of these HLGR isolates carried a Gm(r) determinant, though the hybridization patterns of the plasmids from E. faecalis and E. faecium were different. Although many similarities exist among enterococcal Gm(r) determinants, the results suggest heterogeneity may occur in the flanking regions of resistance elements.

Comparison of preservation mixtures for Helicobacter pylori.

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.

Rapid life-threatening hyperkalemia after addition of amiloride HCl/hydrochlorothiazide to angiotensin-converting enzyme inhibitor therapy.

STUDY OBJECTIVE: To highlight the dangers of a precipitous rise in serum potassium levels in patients at risk for renal insufficiency, already receiving an angiotensin-converting enzyme (ACE) inhibitor, who are given a potassium-sparing diuretic. METHODS: We conducted a retrospective chart review of five patients who were taking the above combination of medications who were seen in our ED with hyperkalemia. RESULTS: All five patients had diabetes and were older than 50 years of age. Except for one patient, they had some degree of renal impairment and all were receiving an ACE inhibitor. Each had amiloride HCl/hydrochlorothiazide added to their therapeutic regimen 8 to 18 days before presenting to our ED with hyperkalemia. Potassium levels were between 9.4 and 11 mEq/L in 4 of the patients; 2 did not respond to resuscitation measures. CONCLUSION: The concomitant use of ACE inhibitor and potassium-sparing diuretic therapy should be avoided. If impossible, weekly monitoring of both renal function and serum potassium should be performed. In the ED patients who are receiving such a combination should receive immediate ECG monitoring.

Cardiac tamponade in Taiwan.

We retrospectively reviewed all of the patients who were treated for cardiac tamponade at Linkou Chang Gung Memorial Hospital between January 1991 and December 1995. There were a total of 112 patients (57 males, 55 females) with a mean age of 51 +/- 14 years (53 +/- 15, 49 +/- 13, respectively). Dyspnea was the most common complaint (85%). The mean blood pressure was 129 +/- 24/78 +/- 17 mmHg, and only 8% had a systolic blood pressure of less than 90 mmHg. Sinus tachycardia was the most frequent electrocardiographic finding (72%, 62/86). Diffuse low voltage was noted in 35% (30/86) of the patients and electrical alternans was seen in 17% (15/86). The mean volume of pericardial effusion was 610 +/- 263 ml. Sixty-five percent of the pericardial effusions were bloody, 31% were serosanguineous, 2% were purulent and 2% were chylous. Overall, 54.5% of the patients had malignant diseases. Of the 61 patients who died, 79% had malignancies. Thirty-five (57%) of these 48 patients had lung cancer. The mean survival time from emergent pericardiocentesis was 3.4 months. In conclusion, non-traumatic cardiac tamponade had a poor prognosis because most patients had malignant etiologies. There is still no definitive treatment for recurrent malignant pericardial effusion-induced cardiac tamponade. Percutaneous pericardiocentesis as clinically required may be the most appropriate treatment, since it is questionable whether such subjects should be subjected to the unnecessary pain and suffering associated with an operative procedure, considering their short mean survival time.

Constitutive fatty acid and enzyme profiles of Mycobacterium species.

Sixty-one strains of Mycobacterium tuberculosis complex and 47 strains of nontuberculous mycobacteria were analyzed for fatty acids and enzyme profiles. Cellular fatty acids were extracted from bacteria, methylated and analyzed by gas liquid chromatography operated either manually (Perkin-Elmer) or by the automatic Microbial Identification System. The major cellular fatty acids in all mycobacterial species were C16:0 and C18:1. Tuberculostearic acid was found in all species with the exception of Mycobacterium gordonae. The fatty acids with a carbon-length longer than 20 could be detected only by conventional gas chromatography. Strains of M. tuberculosis had a high ratio of C26:0 to C24:0, and a relatively low ratio of C14:0 to C15:0. For determination of branched-chain fatty acids, the MIS provided more definitive results. The data indicated that the fatty acid profiles could provide rapid species identification. The results of the enzyme profile analysis using API-ZYM strips showed 39 different patterns from 59 strains of M. tuberculosis, and 41 different patterns from 46 nontuberculous mycobacteria strains, suggesting that enzyme profiles can also be used for strain characterization within the same species.

Clinical challenge--an experience of spontaneous transmural rupture of the oesophagus in Taiwan.

In Taiwan, spontaneous oesophageal rupture is uncommon but the outcome is often lethal because of failure to make an early diagnosis. We have analysed clinical data, management and the risk factors that affect mortality for a consecutive series of 11 patients who had spontaneous oesophageal perforation between 1983 and 1994. The primary symptom was chest or abdominal pain, which was present in 100% of patients; 91% of patients had abnormal chest x-ray (63% pleural effusion, 46% pneumomediastinum, 37% subcutaneous emphysema). In our series of patients the lower thoracic area was the most common location of the perforation (80% of patients. There were no statistically significant differences in mortality due to age, underlying disease, perforation size, location or surgical methods. A poor prognosis seems to be correlated with the time elapsed between the perforation and treatment (especially if > 72 hours) (p < 0.05), respiratory failure (p < 0.05), and heavy contamination of the mediastinum (p < 0.05). The clinical findings depend on the location and time of perforation. History, chest x-ray and oesophagogram are the most useful diagnostic tools. Early diagnosis and treatment are mandatory for these patients.