Pandrug-resistant Pseudomonas aeruginosa among hospitalised patients: clinical features, risk-factors and outcomes

Between 1 January 2003 and 31 December 2003, 37 patients had positive cultures of pandrug-resistant Pseudomonas aeruginosa (PDRPA) resistant to all commercially available anti-pseudomonal antimicrobial agents in Taiwan, including anti-pseudomonal penicillins, ceftazidime, fourth-generation cephalosporins, aztreonam, carbapenems, aminoglycosides and ciprofloxacin. Nineteen (51.4%) patients had PDRPA infections, including pneumonia (17 patients), catheter-related bacteraemia (one patient) and anal abscess (one patient). Eighteen patients were classified as having PDRPA colonisation, based on absence of clinical signs or symptoms of infection. In total, 92 isolates were recovered from various specimens, with the majority (85.9%) recovered from respiratory tract secretions (sputa, bronchial washings and pleural effusions), followed by urine (4.3%) and catheter tips (3.3%). Twenty-eight (75.7%) patients yielded cultures of non-PDR P. aeruginosa isolates before isolation of PDRPA, with a mean period between the first isolation of non-PDR P. aeruginosa and the isolation of PDRPA of 128.3 days. Most patients had received beta-lactam antibiotics, fluoroquinolones or carbapenems for prolonged periods. Univariate analysis showed that PDRPA infection, male gender and the presence of fever at the time of PDRPA isolation were associated with increased mortality.     

Beta-lactamase producing Pseudomonas aeruginosa in hospitalised patients

Beta lactamase continues to be the leading cause of resistance to beta lactam antibiotics in gram-negative bacteria. A total of 50 clinical isolates of Pseudomonas aeruginosa were studied to determine the prevalence of ESBL production in hospital strains and also to study their susceptibility to various other antimicrobial agents. ESBL production was observed in a total of 18/50 (36%) of cases. Most of the ESBL positive isolates showed resistance to 3rd generation cephalosporins including multidrug resistance (MDR) to antibiotics like piperacillin, nalidixic acid, ciprofloxacin, levofloxacin, gentamicin and tobramycin. The ESBL producers however showed good susceptibility to drugs like meropenem, gatifloxacin and amikacin.     

Persistency of Pseudomonas aeruginosa in sputum cultures and clinical outcomes in adult patients with cystic fibrosis

Our objective was to describe the natural history of infection with transmissible and unique strains of P. aeruginosa (PA) in adult CF patients and to determine if clearance of PA from sputum was associated with an improvement in clinical status. This was a 3-year prospective cohort study of adult patients with CF. Sputum was collected at baseline and annually. Rate of decline of FEV1, BMI, exacerbation rate, and time to death or transplant were compared between patients who cleared PA versus those in whom PA was persistent. A total of 373 patients were included in the study, 75% were infected with PA at baseline; 24% were infected with transmissible strains and 51% with unique strains. Patients infected with unique strains were more likely to clear PA from their sputum over 3 years compared to those infected with transmissible strains (19% vs 10%, P=0.05). Declines in FEV1 and rates of pulmonary exacerbations, deaths, or lung transplants were not different between patients who cleared PA compared to those who remained persistently infected. No clinical benefit was identified in patients who cleared PA from sputum compared to those who remained persistently infected.     

Clinical features and outcome of patients with community-acquired Pseudomonas aeruginosa bacteraemia

Cases of community-acquired Pseudomonas aeruginosa bacteraemia (n = 39) that occurred at a tertiary-care hospital during a 5-year period were analysed retrospectively. The commonest underlying diseases were solid tumour (41%) and haematological malignancy (18%). Most (44%) of the patients were neutropenic, and 39% had septic shock at initial presentation. The 30-day attributable mortality rate was 39%. Two previously healthy patients were identified with fatal P. aeruginosa pneumonia with bacteraemia. P. aeruginosa bacteraemia is a fatal infection that should be considered in the differential diagnosis of patients presenting from the community with rapidly progressive sepsis.     

Burden of different beta-lactamase classes among clinical isolates of AmpC-producing Pseudomonas aeruginosa in burn patients: A prospective study

Background:

Pseudomonas aeruginosa is one of the most common pathogens causing infections in burns, and shows increasing resistance to β-lactam antibiotics by producing different classes of beta-lactamases. It is also not unusual to find a single isolate that expresses multiple β-lactamase enzymes, further complicating the treatment options. Thus, in this study, we aimed to determine the coexistence of different beta-lactamase enzymes in clinical isolates of P. aeruginosa in the burn ward.

Materials and Methods:

A total of 101 clinical isolates of P. aeruginosa from the burn ward were identified and tested for the presence of different beta-lactamase enzymes (extended spectrum beta lactamase (ESBL), Amp C and metallo β-lactamases (MBL) from October 2006 to May 2009. In vitro susceptibility pattern of antipseudomonal antibiotics was done by the Kirby Bauer disc diffusion method.

Results:

A total of 33 (32.7%) isolates were confirmed to be positive for AmpC beta-lactamase. Co-production of AmpC along with ESBL and MBL was reported in 24.5% and 45.5% isolates, respectively. A total of 12 (11.9%) isolates were resistant to three or more antibiotic classes (multidrug resistance). Imipenem and piperacillin/tazobactum showed high sensitivity, with 86.1% and 82.2%, respectively.

Conclusion:

This study reveals the high prevalence of multidrug- resistant P. aeruginosa producing beta-lactamase enzymes of different mechanisms in this region from burn patients. The emerging antimicrobial resistance in burn wound pathogens poses serious therapeutic challenge. Thus proper antibiotic policy and measures to restrict the indiscriminate use of cephalosporins and carbapenems should be taken to minimize the emergence of this multiple beta -lactamase producing pathogen.     

Pseudomonas aeruginosa bacteremia in children over ten consecutive years: analysis of clinical characteristics, risk factors of multi-drug resistance and clinical outcomes

This study aimed to evaluate the clinical profiles, antibiotic susceptibility, risk factors of multi-drug resistance (MDR) and outcomes of P. aeruginosa bacteremia in children by retrospective methods at a tertiary teaching children's hospital in Seoul, Korea during 2000-2009. A total of 62 episodes were evaluated and 59 patients (95.2%) had underlying diseases. Multivariate analysis demonstrated that an intensive care unit (ICU) stay within the previous one month was the only independent risk factor for MDR P. aeruginosa bacteremia (odds ratio [OR], 6.8; 95% confidence interval [CI], 1.3-35.8, P = 0.023). The overall fatality rate associated with P. aeruginosa bacteremia was 14.5% (9 of 62). The fatality rate in patients with MDR P. aeruginosa was 57.1%, compared with 9.1% in non-MDR patients (OR 13.3; 95% CI 2.3-77.2, P = 0.006). However, the presence of respiratory difficulty was the only independent risk factor for overall fatality associated with P. aeruginosa bacteremia according to multivariate analysis (OR 51.0; 95% CI 7.0-369.0, P < 0.001). A previous ICU stay and presentation with respiratory difficulty were associated with acquisition of MDR P. aeruginosa and a higher fatality rate, respectively. Future efforts should focus on the prevention and treatment of P. aeruginosa bacteremia in high-risk children.     

Orbital pseudotumor: clinical features and outcomes

To describe the clinical characteristics of orbital pseudotumor, a retrospective analysis was performed on patients with orbital pseudotumor at Siriraj Hospital for ten years. Forty-nine patients (24 males and 25 females; 62 eyes) with a mean age of 43.75 years were included (a mean follow-up of 25 months). Thirty-six patients (73.5%) had unilateral disease. The clinical features were proptosis (79.6%), ocular motor deficit (61.2%), pain (51%), lid swelling or lid mass (44.9%), ptosis (24.5%), and chemosis (18.4%). The most common presenting sign was proptosis (49%). All were treated with corticosteroids with clinical improvement in 40 (81.6%) patients. Ten (83.3%) of 12 patients with visual loss improved with mean recovery time of 10.3 days. Ocular motility recovered in 24 (80%) patients, occurring an average of 17.8 days after initiation of therapy. It is concluded that the clinical features of orbital pseudotumor are varied. Most patients were improved with corticosteroids treatment.     

Statin use and clinical outcomes among pneumonia patients

It was suggested that statin may improve the outcomes of pneumonia patients. However, there are sparse data regarding this topic in ethnic Chinese populations. In the present study, we investigated associations between previous statin use and pneumonia outcomes in Taiwan with a large-scale matched cohort study. A total of 11 576 patients with pneumonia were selected, comprising 2894 patients with previous statin use and 8682 matched patients. We used a separate conditional logistic regression to explore relationships between statin use and each clinical outcome, including ‘intensive care unit admission,’ ‘use of mechanical ventilation,’ ‘acute respiratory failure’ and ‘in-hospital death’. We found that patients who were statin users were 0.81 (95% CI 0.74–0.89), 0.80 (95% CI 0.71–0.89), 0.84 (95% CI 0.75–0.94) and 0.69 times (95% CI 0.57–0.85) less likely to be admitted to the intensive care unit, to have acute respiratory failure, to need mechanical ventilation, and to die in the hospital, respectively, than patients who were not statin users. In addition, it consistently revealed that compared with patients who were not statin users, regular statin users had lower ORs of intensive care unit admission, acute respiratory failure, the use of mechanical ventilation and in-hospital death. However, there were no significant differences in the above adverse outcomes between irregular users of statin and non-statin users. We concluded that patients with regular previous statin use were significantly associated with favourable outcomes during admission for pneumonia in Taiwan.     

Atrial fibrillation among African Americans, Hispanics and Caucasians: clinical features and outcomes from the AFFIRM trial

The Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) study concluded that rate control with anticoagulation was equivalent overall to rhythm control with cardioversion for long-term survival and that anticoagulation reduced the risk of stroke. We compared baseline and follow-up data for three ethnic groups: Caucasians (n=3,599), African Americans (n=265) and Hispanics (n=132). Caucasians were older and more likely male, African Americans were more likely female and hypertensive, and Hispanics had higher prevalence of cardiomyopathy. Survival was better for rate control than rhythm control in Caucasians, equivalent in African Americans and better for rhythm control in Hispanics. Outcomes may be influenced by differential baseline characteristics, but low numbers of African Americans and Hispanics warrant caution in data interpretation. BACKGROUND: The AFFIRM study compared a rate-control strategy to a rhythm-control strategy for the treatment of atrial fibrillation (AF) in patients at high risk for stroke or death. It concluded that the rhythm-control strategy offered no survival advantage, and it also confirmed the value of anticoagulation to prevent complications of AF. Data have not previously been available for specific racial ethnic populations. METHODS: We compared baseline and follow-up data for the patients randomized to rate-control versus rhythm-control in three population groups-Caucasian, African-American and Hispanic. RESULTS: Among 4,060 total patients, 3,599 were Caucasian, 265 were African-American and 132 were Hispanic. At baseline, Caucasians were older and had a higher percentage of males, normal ejection fractions, AF as their only cardiac diagnosis, a prior antiarrhythmic drug failure and less congestive heart failure. African Americans were more likely to be female, had more hypertension and qualified for the study with a first episode of AF, compared to Caucasians. Hispanics had more cardiomyopathy at baseline than Caucasians. Overall survival in Caucasians at five years for the rate-control and rhythm-control groups was 78.9% vs. 76.4%, respectively (p=0.04); for African Americans, 79.0% vs. 69.4% (p=0.22); and for Hispanics, 66.5% vs. 83.9% (p=0.01). Overall, survival was not different between the three populations. However, lower rates of event-free survival were recorded for Hispanics and for African Americans (p=0.0182). CONCLUSIONS: Different survival rates were found for rate-control versus rhythm-control in African-American and Hispanic patients, compared to Caucasian. These findings may be influenced by differences in baseline characteristics, but must be interpreted with caution because of the small sample sizes for African-American and Hispanic participants.     

Beta-lactamase-mediated resistance to extended spectrum cephalosporins among clinical isolates of Pseudomonas aeruginosa.

The role of chromosomal cephalosporinases and secondary beta-lactamases in resistance to extended spectrum cephalosporins in clinical isolates of Pseudomonas aeruginosa was investigated. Strains 687, 59, and 58 expressed an inducible chromosomal cephalosporinase, efficiently enhanced with cefoxitin and imipenem. The inducible activity in strain 802 was produced at a moderately elevated basal level and may be involved in resistance to extended spectrum cephalosporins and aztreonam. All strains produced secondary beta-lactamases inhibited by clavulanate: strains 687, 59, and 58 had carbenicillinases with pIs of 5.7 and 5.3. Strain 802 expressed a secondary beta-lactamase of pI 7.6 which may be a novel extended spectrum beta-lactamase different from known enzymes of P. aeruginosa.     

Lack of effect of shorter turnaround time of microbiological procedures on clinical outcomes: a randomised controlled trial among hospitalised patients in the Netherlands

Shortening the turnaround time of microbiological procedures was associated with an improved clinical outcome in two studies performed in the USA. To study the clinical impact of a shortened turnaround time in a northwest European setting in which an automated system was used for bacterial identification and susceptibility testing, a single-blind, prospective, randomised controlled trial was conducted in a hospital in the Netherlands. All hospitalised patients with a bacterial infection confirmed by culture were randomly assigned to a control (conventional) group or an intervention (rapid) group. Overnight methods were used for identification and susceptibility testing in the control group, while the Vitek 2 system (bioMérieux, Marcy lEtoile, France) was used in the rapid group. In each of three consecutive study periods, accelerating factors were added progressively to the laboratory workflow of the rapid group to increase same-day reporting, whereas methods remained identical in the conventional group. The turnaround time of the microbiological cycle using the Vitek 2 system as compared to conventional methods was studied and the clinical impact of a shortened turnaround time assessed in terms of mortality, morbidity, and cost. For the rapid groups, the turnaround time was significantly shorter for oral reporting of final susceptibility results in all three study periods and for reporting on paper in the third study period. There was no significant difference between groups in any of the clinical impact variables. Vitek 2 results were available for reporting significantly earlier as compared to conventional testing. For the overall patient group in our hospital setting, however, this had no clinical impact.     

Pseudomonas aeruginosa: changes in antibiotic susceptibility, enzymatic activity, and antigenicity among colonial morphotypes

Colonial variants of Pseudomonas aeruginosa have received renewed interest because of their occurrence in sputum cultures of patients with cystic fibrosis. We encountered 11 strains of P. aeruginosa from various body sites of non-cystic fibrosis patients. The strains showed two to three colonial variants, including smooth, rough, and iridescent morphotypes that arose from subculture of a single colony of P. aeruginosa originating from a primary source. The colonial segregants differed in antibiotic susceptibility (resistance to gentamicin, carbenicillin, chloramphenicol, and tetracycline), presence or absence of exoenzymes (gelatinase and elastase), degree of proteolytic activity (caseinase), pigmentation, and antigenicity. These observations suggest that in vivo dissociation with concomitant changes in enzymatic and surface properties might greatly enhance invasiveness. Concurrent differences in antimicrobial susceptibility among the colonial variants could account in some instances for the failure of antibiotic treatment in P. aeruginosa infections in which one would anticipate a positive therapeutic response.     

Admission clinical characteristics and early clinical outcomes among acute ischemic stroke patients

The purpose of the present study was to investigate the association between admission clinical characteristics and outcomes at discharge among acute ischemic stroke patients in the Chinese population.A total of 2,673 patients with acute ischemic stroke were included in the present study.The clinical characteristics at admission and other study variables were collected for all patients.The study outcome was defined as neurological deficiency(National Institute of Health Stroke Scale score ≥ 10) at discharge or in-hospital death.Compared with the subjects without neurological deficiency at discharge or in-hospital death,the subjects with neurological deficiency at discharge or in-hospital death had a significantly higher prevalence of hyperglycemia or history of atrial fibrillation at admission.Age≥ 80 years,hyperglycemia,hypertension,and history of atrial fibrillation were significantly associated with neurological deficiency at discharge or in-hospital death after adjustment for other variables.It is concluded that old age(≥ 80 years),hyperglycemia,hypertension and history of atrial fibrillation are significantly associated with neurological deficiency at discharge or in-hospital death among patients with acute ischemic stroke.     

Antigenic heterogeneity among pyocins of Pseudomonas aeruginosa.

We investigated the effect of FeSO4 on phagocytosis-associated, increased oxidative metabolism via the hexose monophosphate shunt, with special attention to its effect on H2O2 levels. The availability of glutathione peroxidase and glutathione reductase for H2O2 disposal and hexose monophosphate shunt stimulation also are evaluated. The results show an impairment of phagocytosis-associated hexose monophosphate shunt activity together with an increase both of resting and phagocytosing formate oxidation. These apparently paradoxical findings are resolved by demonstrating a direct enhancement of formate oxidation by FeSO4 in a cell-free system. In addition, measurement of H2O2 concentrations via scopoletin fluorescence shows reduction of H2O2 by FeSO4. There is no effect on either glutathione peroxidase or glutathione reductase activities. These data suggest that one mechanism of FeSO4 impairment of microbicidal activity is by its removal of H2O2.     

Analysis of risk-factors among patients with Crimean-Congo haemorrhagic fever virus infection: severity criteria revisited

The aim of this study was to determine the predictors of mortality among patients infected with Crimean-Congo haemorrhagic fever (CCHF) virus. Among patients with acute febrile syndrome, characterised by malaise, bleeding, leukopenia and thrombocytopenia, who were admitted to hospital during the spring and summer of 2002-2004, 54 had positive IgM and/or PCR results for CCHF virus in blood or tissue. The overall case fatality rate was 7.4%. Among the fatalities, haematemesis (p 0.009), melaena (p 0.001) and somnolence (p 0.022) were more common, the median platelet count was significantly lower (10,600/mL vs. 20,000/mL; p 0.038), the mean prothrombin time (27 s vs. 16 s; p 0.002) and mean activated partial thromboplastin time (73 s vs. 44 s; p < 0.001) were longer, and the mean alanine transferase (ALT) level (1,125 vs. 331; p < 0.001), the mean aspartate transferase (AST) level (3,118 vs. 913; p 0.004) and the mean fibrinogen level (119 vs. 340; p 0.012) were higher. Serum IgM and IgG against CCHF virus was detected in 25% and 0%, respectively, of fatal cases, compared with 94% and 62%, respectively, of cases with favourable outcomes. Oral ribavirin was prescribed to 22 (41%) patients. Of the four fatal cases, it was the intention to prescribe ribavirin to three patients, but this was not possible because of haematemesis and melaena. Higher levels of AST (>or= 700 U/L) and ALT (>or= 900 U/L) are suggested for use as severity criteria. Oral ribavirin was not effective for patients with haematemesis, and intravenous ribavirin is necessary for treatment of CCHF.     

Depression among hospitalised medically ill patients: a two-stage screening study

BACKGROUND: There is wide variability in prevalence of depression in the physically ill. Moreover, data from the developing world is scarce. METHODS: Consecutive patients between the age 20-60 years and excluding those with malignancies and neurological illnesses, admitted to medical units (N=176), were screened with Beck's Depression Inventory (BDI). Those scoring more than 10 on BDI (N=55) were assessed with the Schedule for Clinical Assessment in Neuropsychiatry (SCAN). Age/sex matched healthy relatives served as controls. RESULTS: Thirty two percent (32%) of patients scored more than 10 on the BDI. None among controls scored more than the cut-off on BDI. Second-stage screening with SCAN on 33 subjects yielded a figure of 17% for depressive syndrome among the physically ill. Depression was mostly of the mild to moderate variety. CONCLUSIONS: High rates of depression were detected among physically ill hospitalised patients. Perhaps, differences in instruments used and population screened accounted for this. CLINICAL IMPLICATIONS: Need for increasing awareness as well as improving methods of detecting depression in physically ill is underscored. LIMITATIONS: a significant number of patients who screened positive on the BDI could not be interviewed with the SCAN for various reasons. Thus figures obtained after second stage screening are likely to be an underestimate.     

Morphologic and microbiologic features of Pseudomonas aeruginosa pneumonia in normal hamsters

A model of pneumonia due to Pseudomonas aeruginosa was produced in hamsters by an intratracheal bolus instillation of microorganisms. Sequential lung changes from 4 hr through 11 days were studied by morphologic and microbiologic methods. Hamsters inoculated with greater than 10(6) pseudomonads survived but consistently had histologic evidence of mild bronchopneumonia 24 hr postinoculation, whereas a severe bronchopneumonia and a 100% mortality were elicited with a 10(8) inoculum of organisms in 0.5 ml phosphate-buffered saline (PBS). An inoculum of 10(7) pseudomonads/0.5 ml PBS was then used to define the changes in the bacterial population in Pseudomonas pneumonia and to obtain serial histopathologic observations. Quantitative lung cultures obtained within 1 hr postinoculation demonstrated a mean of 10(6) colony forming units per lung, and none of the hamsters were bacteremic. However, by 24 hr bacterial counts had increased and all animals were bacteremic. Bacterial proliferation continued through 48 hr; however, the number of bacteremic animals had decreased. By 72 hr, bacterial counts had decreased with total Pseudomonas clearance noted by 120 hr. A striking polymorphonuclear leukocyte-rich alveolar exudate was present by 12 hr. Pseudomonas "vasculitis" was evident by 24 hr. The evolution of this vascular lesion correlated with the bacteremic state of the hamsters. By 11 days, resolution of the pneumonic process was seen. The macroscopic and microscopic features of this hamster model of Pseudomonas pneumonia are very similar to those reported in infected patients.