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Biomedical subjects

D L Paterson

Publications and source records attributed to D L Paterson.

At least 37 records · Page 2Linked to original sources
PubMed2000

Recommendation for treatment of severe infections caused by Enterobacteriaceae producing extended-spectrum beta-lactamases (ESBLs).

Extended-spectrum beta-lactamase (ESBL)-producing organisms are a global problem. No randomized controlled trials have ever been performed to guide optimal treatment. However, in vitro studies and observational studies strongly suggest that carbapenems (imipenem or meropenem) should be regarded as drugs of choice for serious infections due to ESBL-producing organisms. Other beta-lactam antibiotics (cefepime, beta-lactam/beta-lactamase inhibitor combinations) are not suitable as first-line therapy. The increasing frequency of the association between quinolone resistance and ESBL production have greatly limited the role of this class of antibiotic against ESBL producers.

Anti-Bacterial Agents↗
PubMed2000

Methicillin-resistant Staphylococcus aureus: the other emerging resistant gram-positive coccus among liver transplant recipients.

We undertook a study of the characteristics and clinical impact of infections due to methicillin-resistant Staphylococcus aureus (MRSA) after liver transplantation. Of 165 patients who received liver transplants at our institution from 1990 through 1998, 38 (23%) developed MRSA infections. The predominant sources of infection were vascular catheters (39%; n=15), wound (18%; n=7), abdomen (18%; n=7), and lung (13%; n=5). A significant increase in MRSA infections (as a percentage of transplant patients infected per year) occurred over time (P=.0001). This increase was greater among intensive care unit patients (P=.001) than among nonintensive care unit hospital patients (P=.17). Cytomegalovirus seronegativity (P=.01) and primary cytomegalovirus infection were significantly associated with MRSA infections (P=.005). Thirty-day mortality among patients with MRSA infections was 21% (8/38). Mortality was 86% in patients with bacteremic MRSA pneumonia or abdominal infection and 6% in those with catheter-related bacteremia (P=.004). Thus the incidence of MRSA infection has increased exponentially among our liver transplant recipients since 1990. These infections have unique risk factors, time of onset, and a significant difference in site-specific mortality; deep-seated bacteremic infections, in particular, portend a grave outcome.

Adult↗
PubMed2000

Epidemiology of ciprofloxacin resistance and its relationship to extended-spectrum beta-lactamase production in Klebsiella pneumoniae isolates causing bacteremia.

A prospective study of Klebsiella pneumoniae bacteremia was performed in 12 hospitals in 7 countries. Of 452 episodes of bacteremia, 25 (5.5%) were caused by K. pneumoniae that was resistant in vitro to ciprofloxacin. Extended-spectrum beta-lactamase (ESBL) production was detected in 15 (60%) of 25 ciprofloxacin-resistant isolates, compared with 68 (16%) of 427 ciprofloxacin-susceptible strains (P=.0001). Multivariate analysis revealed that risk factors for ciprofloxacin resistance in K. pneumoniae included prior receipt of a quinolone (P=.0065) and an ESBL-producing strain (P=.012). In all, 18% of ESBL-producing isolates were also ciprofloxacin-resistant. Pulsed-field gel electrophoresis showed that 11 of the 15 ciprofloxacin-resistant ESBL-producing strains belonged to just 4 genotypes, suggesting that patient-to-patient transmission of such strains occurred. The close relationship between ESBL production and ciprofloxacin resistance is particularly worrisome because the first reported instance of plasmid-mediated ciprofloxacin resistance has been in an isolate of K. pneumoniae also possessing an ESBL.

Anti-Infective Agents↗
PubMed1999

Intraoperative hypothermia is an independent risk factor for early cytomegalovirus infection in liver transplant recipients.

BACKGROUND: Early cytomegalovirus (CMV) reactivation infections have been found to be associated with a number of stress responses such as severe bacterial infection. Intraoperative hypothermia is known to be a significant physiological stressor. Hence, we sought to evaluate a relationship between intraoperative hypothermia during liver transplantation and early CMV infection. METHODS: Relationships between intraoperative hypothermia and early CMV infection were assessed using univariate and multivariate analysis. RESULTS: There were 11 of 100 patients who had CMV infection detected within the first 30 days after the transplant and 16 of 100 in the next 3 months after the transplant. The median intraoperative temperature (34.4 degrees C) of those who subsequently developed early CMV infection was significantly lower than that in patients who did not develop early CMV infection (35.3 degrees C; P = 0.032). Multivariate analysis showed that only hypothermia was an independent predictor of early CMV infection (odds ratio 2.8, 95% confidence intervals 1.2-6.4; P = 0.047). CONCLUSIONS: Intraoperative hypothermia during liver transplantation increases the risk of CMV infection in the 1st month postoperatively and active warming seems to reduce this risk.

Body Temperature↗
PubMed1999

Reduced susceptibility of Staphylococcus aureus to vancomycin--a review of current knowledge.

Antibiotic options for patients with methicillin resistant Staphylococcus aureus infections are severely limited. Unfortunately, infections with S. aureus with reduced susceptibility to vancomycin and teicoplanin have been recently reported for the first time. Commonly used laboratory methods for determining antibiotic susceptibility may be inadequate for detecting reduced susceptibility to vancomycin. Even though no confirmed cases have yet been detected in Australia, a high index of suspicion must be maintained for the occurrence of such organisms. Strategies for prevention of the spread of S. aureus with reduced susceptibility to vancomycin should be prepared by Australian hospitals prior to their first cases being identified. This article outlines the background to this developing issue and discusses laboratory methods and findings, with some current recommendations for diagnostic laboratories.

Australia↗
PubMed1999

Encephalopathy associated with human herpesvirus 6 in a liver transplant recipient.

Recent reports have documented human herpesvirus 6 (HHV-6) as a cause of high fever, bone marrow depression, and rash in liver transplant recipients in the absence of another known pathogen. We describe a 49-year-old liver transplant recipient who developed confusion, occipital headache, and involuntary movements of the limbs 3 weeks after orthotopic liver transplantation. HHV-6 was detected in the peripheral blood using a rapid culture assay. Examination of cerebrospinal fluid by polymerase chain reaction for HHV-6 was also positive. No other pathogens were identified. The patient improved after commencement of intravenous ganciclovir therapy. This case suggests HHV-6 needs to be considered in the differential diagnosis of unexplained confusion in liver transplant recipients.

Antiviral Agents↗
PubMed1999

Successful treatment of post-influenza pseudomembranous necrotising bronchial aspergillosis with liposomal amphotericin, inhaled amphotericin B, gamma interferon and GM-CSF.

A case of aspergillus tracheobronchitis following influenza A infection in an immunocompetent 35 year old woman is described that required prolonged mechanical ventilation for airways obstruction. Treatment included liposomal amphotericin, inhaled amphotericin, gamma interferon and GM-CSF. Liposomal amphotericin therapy was associated with reversible hepatosplenomegaly. Inhaled corticosteroids with continued antifungal therapy were used for the management of severe recurrent airway obstruction. After a prolonged course of treatment she survived with fixed airways obstruction unresponsive to corticosteroids.

Adult↗
PubMed1998

Central nervous system lesions in liver transplant recipients: prospective assessment of indications for biopsy and implications for management.

BACKGROUND: Precise diagnosis of central nervous system (CNS) lesions in liver transplant recipients remains problematic. Brain biopsies are often not feasible as a result of coagulopathy. We sought to determine whether selected clinical or radiologic characteristics can predict the likely etiology of CNS lesions in liver transplant recipients and thus obviate the need for diagnostic brain biopsies. METHODS: A 4-year prospective, observational, cohort study was conducted at liver transplant centers at four geographically diverse medical institutions. A total of 1730 consecutive liver transplant recipients were evaluated for CNS lesions; 60 patients with radiologically documented CNS lesions comprised the study sample. RESULTS: Vascular events (52%, 31/60), infections (181%, 11/60), immunosuppressive associated leukoencephalopathy (12%, 7/60), central pontine myelinolysis (8%, 5/60), and malignancy (3%, 2/60) were the predominant etiologies of CNS lesions. CNS lesions were most likely to occur within 30 days of transplantation (43%, 26/60); central pontine myelinolysis, subdural hematoma, acute infarcts, and Aspergillus brain abscesses were the predominant etiologies during this time. All brain abscesses were fungal; 73% (8/11) of these patients concurrently had documented extraneural (pulmonary) infection as a result of the same fungal pathogen. Thus, a diagnostic brain biopsy is not warranted in these patients. Patients on dialysis were more likely to have ischemic or infectious CNS lesions (P=0.03). Vascular events were more likely to occur in repeat transplant recipients (P=0.03). Twenty-five percent (15/60) of the CNS lesions occurred more than 1 year after transplantation; small vessel ischemic lesions, malignancy, or non-Aspergillus fungal brain abscesses accounted for all such lesions. CONCLUSIONS: A presumptive etiologic diagnosis can be established in a vast majority of CNS lesions in liver transplant recipients based on identifiable presentation that includes time of onset, unique risk factors, and neuroimaging characteristics. Empiric therapy of brain abscesses in liver transplant recipients should include antifungal and not antibacterial agents.

Adult↗
PubMed1998

Infectious complications occurring in liver transplant recipients receiving mycophenolate mofetil.

BACKGROUND: Mycophenolate mofetil (MMF) is a new immunosuppressive agent that is gaining widespread use in solid organ transplantation recipients. A comprehensive assessment of infectious complications after its use after liver transplantation has never been assessed. METHODS: Bacterial, fungal, and viral infections occurring after transplantation were compared for a cohort of consecutive liver transplant recipients who received MMF (because of suspected tacrolimus-related nephrotoxicity or neurotoxicity) and a cohort who did not receive the drug. All patients received a tacrolimus-based primary immunosuppressive protocol. RESULTS: Biopsy-proven acute rejection episodes within the first 6 months after transplant occurred in 6% of MMF-treated patients but in 30% of those who did not receive MMF (P=0.07). No significant differences were found in occurrence of cytomegalovirus infection or disease, Pneumocystis carinii, Aspergillus, or other fungal infection and hepatitis C virus recurrence between MMF-treated and untreated patients. Bacterial infections were more common in MMF-treated patients, but this cohort had a prolonged intensive care unit stay compared with patients who did not receive MMF. None of the MMF-treated patients with bacterial infection had leukopenia. CONCLUSIONS: MMF use does not appear to be associated with an significantly increased risk of infection occurring after liver transplantation and is associated with fewer episodes of acute rejection.

Cohort Studies↗
PubMed1998

Should third-generation cephalosporins be the empirical treatment of choice for severe community-acquired pneumonia in adults?

The choice of empirical treatment for community-acquired pneumonia (CAP) is highly controversial. Our survey of 42 Australian emergency department doctors showed that monotherapy with a third-generation cephalosporin was the preferred regimen for severe CAP (14/42; 33%). We argue that cheaper regimens with a narrower spectrum are likely to be just as effective as third-generation cephalosporins and will have fewer adverse effects on the microbial ecology of hospitals. We suggest penicillin or ampicillin (to cover pneumococci--even if penicillin "resistant"--and Haemophilus influenzae), plus a macrolide (e.g., azithromycin or erythromycin; to cover Legionella and other "atypical" pathogens), plus a single large dose of an aminoglycoside (e.g., gentamicin; to cover gram-negative bacilli such as Klebsiella pneumoniae) as empirical therapy for severe CAP.

Adult↗
PubMed1998

Treatment options for chronic prostatitis due to vancomycin-resistant Enterococcus faecium.

Prostatitis due to vancomycin-resistant enterococci has not been previously described. Reported here is a case of chronic prostatitis due to Enterococcus faecium, resistant to vancomycin, ampicillin, ciprofloxacin and doxycycline, in a 42-year-old liver transplant recipient. Treatment with a combination of rifampin and nitrofurantoin for 6 weeks resulted in long-lasting cure. Other antimicrobial agents active in vitro against vancomycin-resistant enterococci, such as quinupristin/ dalfopristin and chloramphenicol, are unlikely to achieve sufficient prostatic tissue levels to be successfully utilized for treatment of this condition.

Adult↗
PubMed1998

Risk factors for toxicity in elderly patients given aminoglycosides once daily.

OBJECTIVE: To determine the risk factors for aminoglycoside toxicity in the elderly. DESIGN: Prospective observational study. SETTING: Acute care teaching hospital serving predominantly veterans. PARTICIPANTS: Consecutive patients aged 70 years and over receiving aminoglycosides. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thirteen (15%) of 88 patients developed aminoglycoside-related nephrotoxicity and 3 (3.4%) developed otovestibular toxicity. Multivariate analysis showed that increasing duration of aminoglycoside therapy was the only factor significantly associated with development of toxicity. Elevated baseline serum creatinine level (p = .02) and use of allopurinol (p = .03) were risk factors specifically for nephrotoxicity. Only 2 (3.9%) of 51 patients receiving aminoglycosides 7 or fewer days developed nephrotoxicity, as compared with 11 (30%) of 37 receiving the drugs for 8 to 14 days and 4 (50%) of 8 treated for more than 14 days. CONCLUSIONS: Although toxicity is common in elderly patients treated with aminoglycosides, limiting the duration of aminoglycoside therapy to less than a week can substantially reduce risk of toxicity.

Aged↗
PubMed1998

Failure to detect Chlamydia pneumoniae in atherosclerotic plaques of Australian patients.

Chlamydia pneumoniae is a recently reported, but common, respiratory tract pathogen. The organism has been detected by electron microscopy, immunocytochemistry, polymerase chain reaction (PCR) and recently culture within atherosclerotic plaques, suggesting a possible association between C. pneumoniae infection and atherosclerosis. Interestingly this association has not been found by all researchers. We examined 17 carotid endarterectomy specimens, 16 carotid arteries and 16 coronary arteries from autopsy specimens. They were examined by PCR for the presence of C. pneumoniae. In none of the 49 atherosclerotic samples examined was C. pneumoniae detected. The sensitivity of our PCR assay was rigorously tested and found to detect consistently fewer than ten elementary bodies. The association between C. pneumoniae and atherosclerosis is intriguing but has not yet been demonstrated in Australian patients.

Arteriosclerosis↗
PubMed1998

Monitoring of serum aminoglycoside levels with once-daily dosing.

There is considerable confusion as to how to monitor serum aminoglycoside levels when using once-daily dosing. At least five methods are in use in Australia. We prospectively assessed 100 consecutive once-daily courses of gentamicin or tobramycin, during which 120 pre-dose and 213 sets of immediate post-dose and six hour post-dose levels were taken. By using the six hour post-dose level we were able to compare dosage recommendations made using methods known as ALADDIN, DOSECALC and the Australian Antibiotic Guidelines nomogram (AAGN). There were statistically significant differences in the doses recommended by each method. When comparing each of the three methods, at least 25% of dosage recommendations differed by more than 80 mg per dose. Although we have not been able to determine the clinical significance of these differences, we are concerned that methods used in dosage adjustment of aminoglycosides differ so widely in their recommendations. Presumably the ALADDIN method, which utilises two post-dose levels to determine an area under aminoglycoside concentration-time curve, gives more accurate pharmacokinetic information than methods which rely on a single level. Comparative cost-effectiveness studies of different methods, although in practice difficult to perform, should be undertaken to resolve the optimal management of patients receiving aminoglycosides once-daily.

Adult↗