Incidence of Hospital-Acquired Pneumonia,Bacteraemia and Urinary Tract Infections in Patients with Haematological Malignancies, 2004–2010: A Surveillance-Based Study

Objective

This study charted incidence trends of hospital-acquired (HA) pneumonia, bacteraemia and urinary tract infections (UTI) in a haematology department.

Methods

Prospective surveillance of hospital-acquired infections (HAI) was undertaken in a 42-bed haematology department of a university hospital. All patients hospitalized ≥48 hours between 1^st January 2004 and 31^st December 2010 were included. Definitions of HAI were based on a standardized protocol. The incidence was the number of events per 1000 patient-days at risk; only the first HAI was counted. Multivariate Poisson regression was fitted to assess temporal trends.

Results

Among 3 355 patients (58 063 patient-days at risk) included, 1 055 (31%) had HAI. The incidence of HA pneumonia, HA bacteraemia and HA UTI was respectively 3.3, 12.0 and 2.9 per 1000 patient-days at risk. HA bacteraemia incidence increased by 11% (95% confidence interval: +6%, +15%, P<0.001) per year, independently of neutropenia, central venous catheterization (CVC) and haematological disease. The incidences of HA pneumonia and HA UTI were stable. The most frequently isolated pathogens were Aspergillus spp. (59.2%) for pneumonia, coagulase-negative Staphylococcus (44.2%) for bacteraemia and enterobacteria (60%) for UTI.

Conclusion

The incidence of bacteraemia increased, indicating that factors other than CVC exposure, including chemotherapy with its impact on the immune system, could explain this trend. Further analytic studies are needed to explore the factors that could explain this trend.     

Update on Inpatient Glycemic Control in Hospitals in the United States

ObjectiveTo provide data on glucose control in hospitals in the United States, analyzing measurements from the largest number of facilities to date.MethodsPoint-of-care bedside glucose (POC-BG) test results were extracted from 575 hospitals from January 2009 to December 2009 by using a laboratory information management system. Glycemic control for patients in the intensive care unit (ICU) and non-ICU areas was assessed by calculating patient-day-weighted mean POC-BG values and rates of hypoglycemia and hyperglycemia. The relationship between POC-BG levels and hospital characteristics was determined.ResultsA total of 49,191,313 POC-BG measurements (12,176,299 ICU and 37,015,014 non-ICU values) were obtained from 3,484,795 inpatients (653,359 in the ICU and 2,831,436 in non-ICU areas). The mean POC-BG was 167 mg/dL for ICU patients and 166 mg/dL for nonICU patients. The prevalence of hyperglycemia (> 180 mg/ dL) was 32.2% of patient-days for ICU patients and 32.0% of patient-days for non-ICU patients. The prevalence of hypoglycemia (< 70 mg/dL) was 6.3% of patient-days for ICU patients and 5.7% of patient-days for non-ICU patients. Patient-day-weighted mean POC-BG levels varied on the basis of hospital size (P < .01), type (P < .01), and geographic location (P < .01) for ICU and non-ICU patients, with larger hospitals (≥ 400 beds), academic hospitals, and US hospitals in the West having the lowest mean POC-BG values. The percentage of patient-days in the ICU characterized by hypoglycemia was highest among larger and academic hospitals (P < .05) and least among hospitals in the Northeast (P < .001).ConclusionHyperglycemia is common in hospitals in the United States, and glycemic control may vary on the basis of hospital characteristics. Increased hospital participation in data collection may support a national benchmarking process for the development of optimal practices to manage inpatient hyperglycemia. (Endocr Pract. 2011;17:853-861)     

Incidence of and Risk Factors for Infection or Colonization of Vancomycin-Resistant Enterococci in Patients in the Intensive Care Unit

The prevalence of vancomycin-resistant enterococci (VRE) colonization or infection in the hospital setting has increased globally. Many previous studies had analysed the risk factors for acquiring VRE, based on cross-sectional studies or prevalent cases. However, the actual incidence of and risk factors for VRE remain unclear. The present study was conducted in order to clarify the incidence of and risk factors for VRE in the intensive care unit (ICU). From 1^st April 2008 to 31^st March 2009, all patients admitted to a surgical ICU (SICU) were put on active surveillance for VRE. The surveillance cultures, obtained by rectal swab, were taken on admission, weekly while staying in the SICU, and on discharge from the SICU. A total of 871 patients were screened. Among them, 34 were found to carry VRE before their admission to the SICU, and 47 acquired VRE during their stay in the SICU, five of whom developed VRE infections. The incidence of newly acquired VRE during ICU stay was 21.9 per 1000 patient-days (95% confidence interval [CI], 16.4–29.1). Using multivariate analysis by logistic regression, we found that the length of ICU stay was an independent risk factor for new acquisition of VRE. In contrast, patients with prior exposure to first-generation cephalosporin were significantly less likely to acquire VRE. Strategies to reduce the duration of ICU stay and prudent usage of broad-spectrum antibiotics are the keys to controlling VRE transmission.     

Success rate of split-thickness skin grafting of chronic venous leg ulcers depends on the presence of Pseudomonas aeruginosa: a retrospective study

The last years of research have proposed that bacteria might be involved in and contribute to the lack of healing of chronic wounds. Especially it seems that Pseudomonas aeruginosa play a crucial role in the healing. At Copenhagen Wound Healing Centre it was for many years clinical suspected that once chronic venous leg ulcers were colonized (weeks or months preoperatively) by P. aeruginosa, the success rate of skin grafting deteriorated despite aggressive treatment. To investigate this, a retrospective study was performed on the clinical outcome of 82 consecutive patients with chronic venous leg ulcers on 91 extremities, from the 1^st of March 2005 until the 31^st of August 2006. This was achieved by analysing the microbiology, demographic data, smoking and drinking habits, diabetes, renal impairment, co-morbidities, approximated size and age of the wounds, immunosuppressive treatment and complicating factors on the clinical outcome of each patient. The results were evaluated using a Student T-test for continuous parameters, chi-square test for categorical parameters and a logistic regression analysis to predict healing after 12 weeks. The analysis revealed that only 33,3% of ulcers with P. aeruginosa, isolated at least once from 12 weeks prior, to or during surgery, were healed (98% or more) by week 12 follow-up, while 73,1% of ulcers without P. aeruginosa were so by the same time (p = 0,001). Smoking also significantly suppressed the outcome at the 12-week follow-up. Subsequently, a logistic regression analysis was carried out leaving P. aeruginosa as the only predictor left in the model (p = 0,001). This study supports our hypothesis that P. aeruginosa in chronic venous leg ulcers, despite treatment, has considerable impact on partial take or rejection of split-thickness skin grafts.     

Tracking Down Antibiotic-Resistant Pseudomonas aeruginosa Isolates in a Wastewater Network

The Pseudomonas aeruginosa-containing wastewater released by hospitals is treated by wastewater treatment plants (WWTPs), generating sludge, which is used as a fertilizer, and effluent, which is discharged into rivers. We evaluated the risk of dissemination of antibiotic-resistant P. aeruginosa (AR-PA) from the hospital to the environment via the wastewater network. Over a 10-week period, we sampled weekly 11 points (hospital and urban wastewater, untreated and treated water, sludge) of the wastewater network and the river upstream and downstream of the WWTP of a city in eastern France. We quantified the P. aeruginosa load by colony counting. We determined the susceptibility to 16 antibiotics of 225 isolates, which we sorted into three categories (wild-type, antibiotic-resistant and multidrug-resistant). Extended-spectrum β-lactamases (ESBLs) and metallo-β-lactamases (MBLs) were identified by gene sequencing. All non-wild-type isolates (n = 56) and a similar number of wild-type isolates (n = 54) were genotyped by pulsed-field gel electrophoresis and multilocus sequence typing. Almost all the samples (105/110, 95.5%) contained P. aeruginosa, with high loads in hospital wastewater and sludge (≥3×10⁶ CFU/l or/kg). Most of the multidrug-resistant isolates belonged to ST235, CC111 and ST395. They were found in hospital wastewater and some produced ESBLs such as PER-1 and MBLs such as IMP-29. The WWTP greatly reduced P. aeruginosa counts in effluent, but the P. aeruginosa load in the river was nonetheless higher downstream than upstream from the WWTP. We conclude that the antibiotic-resistant P. aeruginosa released by hospitals is found in the water downstream from the WWTP and in sludge, constituting a potential risk of environmental contamination.     

Molecular characterization of clinical and environmental Pseudomonas aeruginosa isolated in a burn center

In burn centers, Pseudomonas aeruginosa acts as a major cause of nosocomial infections. Therefore, this study aimed to characterize molecularly P. aeruginosa isolates collected from environmental samples and burn patients. A total of 78 strains (including 58 clinical and 20 environmental isolates) of the P. aeruginosa were collected from Beasat hospital of Hamadan, west of Iran, and was identified using API 20NE. The disk diffusion method according to the CLSI was applied for determination of the antimicrobial resistance. Moreover, the microtiter plate test was used for the quantification of Biofilm formation. The genomic features of the isolated strains was evaluated using Pulsed Field Gel Electrophoresis (PFGE). We found that 94.8% of clinical and 80% environmental isolates were capable of forming biofilm. The rate of MDR in clinical and environmental isolates was 51.7% and 40%, respectively. A significant relationship was observed between biofilm formation capability and multiple drug resistance (p < 0.05). PFGE typing showed 11 different clusters with two major clusters A with 30 (38.5%) and B with 14 (17.9%) members, containing up to 56.4% of all isolates. There was no relationship between biofilm formation ability and antibiotic resistance patterns with PFGE patterns. According to the results, the clonal spread of environmental P. aeruginosa isolates is associated with clinical isolates, and both environmental and clinical isolates are attributed to a high prevalence of the antibiotic resistance and biofilm formation ability. This study highlighted that the prevention programs should be implemented in the hospital environment to control the spread of P. aeruginosa in burn units.     

A relationship between Pseudomonal growth behaviour and cystic fibrosis patient lung function identified in a metabolomic investigation

Chronic polymicrobial lung infections in adult cystic fibrosis patients are typically dominated by high levels of Pseudomonas aeruginosa. Determining the impact of P. aeruginosa growth on airway secretion composition is fundamental to understanding both the behaviour of this pathogen in vivo, and its relationship with other potential colonising species. We hypothesised that the marked differences in the phenotypes of clinical isolates would be reflected in the metabolite composition of spent culture media. ¹H NMR spectroscopy was used to characterise the impact of P. aeruginosa growth on a synthetic medium as part of an in vitro CF lower airways model system. Comparisons of 15 CF clinical isolates were made and four distinct metabolomic clusters identified. Highly significant relationships between P. aeruginosa isolate cluster membership and both patient lung function (FEV₁) and spent culture pH were identified. This link between clinical isolate growth behaviour and FEV₁ indicates characterisation of P. aeruginosa growth may find application in predicting patient lung function while the significant divergence in metabolite production and consumption observed between CF clinical isolates suggests dominant isolate characteristics have the potential to play both a selective role in microbiota composition and influence pseudomonal behaviour in vivo.     

Laboratory-Based Prospective Surveillance for Community Outbreaks of Shigella spp. in Argentina

Background

To implement effective control measures, timely outbreak detection is essential. Shigella is the most common cause of bacterial diarrhea in Argentina. Highly resistant clones of Shigella have emerged, and outbreaks have been recognized in closed settings and in whole communities. We hereby report our experience with an evolving, integrated, laboratory-based, near real-time surveillance system operating in six contiguous provinces of Argentina during April 2009 to March 2012.

Methodology

To detect localized shigellosis outbreaks timely, we used the prospective space-time permutation scan statistic algorithm of SaTScan, embedded in WHONET software. Twenty three laboratories sent updated Shigella data on a weekly basis to the National Reference Laboratory. Cluster detection analysis was performed at several taxonomic levels: for all Shigella spp., for serotypes within species and for antimicrobial resistance phenotypes within species. Shigella isolates associated with statistically significant signals (clusters in time/space with recurrence interval ≥365 days) were subtyped by pulsed field gel electrophoresis (PFGE) using PulseNet protocols.

Principal Findings

In three years of active surveillance, our system detected 32 statistically significant events, 26 of them identified before hospital staff was aware of any unexpected increase in the number of Shigella isolates. Twenty-six signals were investigated by PFGE, which confirmed a close relationship among the isolates for 22 events (84.6%). Seven events were investigated epidemiologically, which revealed links among the patients. Seventeen events were found at the resistance profile level. The system detected events of public health importance: infrequent resistance profiles, long-lasting and/or re-emergent clusters and events important for their duration or size, which were reported to local public health authorities.

Conclusions/Significance

The WHONET-SaTScan system may serve as a model for surveillance and can be applied to other pathogens, implemented by other networks, and scaled up to national and international levels for early detection and control of outbreaks.     

Anaerobic Transfer of Antibiotic Resistance from Pseudomonas aeruginosa

Pseudomonas aeruginosa, an opportunistic pathogen that often initiates infections from a reservoir in the intestinal tract, may donate or acquire antibiotic resistance in an anaerobic environment. Only by including nitrate and nitrite in media could antibiotic-resistant and -sensitive strains of P. aeruginosa be cultured in a glove box isolator. These anaerobically grown cells remained sensitive to lytic phage isolated from sewage. After incubation with a phage lysate derived from P. aeruginosa 1822, anaerobic transfer of antibiotic resistance to recipients P. aeruginosa PS8EtBr and PS8EtBrR occurred at frequencies of 6.2 × 10⁻⁹ and 5.0 × 10⁻⁸ cells per plaque-forming unit, respectively. In experiments performed outside the isolator, transfer frequencies to PS8EtBr and PS8EtBrR were higher, 1.3 × 10⁻⁷ and 6.5 × 10⁻⁸ cells per plaque-forming unit, respectively. When P. aeruginosa 1822 was incubated aerobically with Escherichia coli B in medium containing nitrate and nitrite, the maximum concentration of carbenicillin-resistant E. coli B reached 25% of the total E. coli B population. This percentage declined to 0.01% of the total E. coli B population when anaerobically grown P. aeruginosa 1822 and E. coli B were combined and incubated in the glove box isolator. The highest concentration of the recipient population converted to antibiotic resistance occurred after 24 h of aerobic incubation, when an initially high donor/recipient ratio (>15) of cells was mixed. These data indicate that transfer of antibiotic resistance either by transduction between Pseudomonas spp. or by conjugation between Pseudomonas sp. and E. coli occurs under strict anaerobic conditions, although at lower frequencies than under aerobic conditions.     

Transferable Carbenicillin Resistance in <Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis>

IN 1969, after carbenicillin had been in use for three years in this unit, highly resistant strains of Pseudomonas aeruginosa were isolated for the first time¹. Because these resistant strains included, from their first appearance, representatives of two unrelated types, it seemed likely that the resistance was transferable; this hypothesis was supported by experiments showing the transfer of carbenicillin resistance between Ps. aeruginosa and Escherichia coli K12 in vitro and in vivo^2–4;. The resistant Ps. aeruginosa produced a penicillinase (β lactamase) similar to that normally produced by some strains of Enterobacteria and different from that normally produced by Ps. aeruginosa^2,3, so it seemed likely that the Ps. aeruginosa had initially acquired resistance by the transfer of an R factor from a carbenicillin-resistant member of the Enterobacteriaceae colonizing the same burn. This hypothesis is now supported by a study on strains of Enterobacteria and Ps. aeruginosa isolated in a number of hospitals. We have also found evidence suggesting that Ps. aeruginosa which has acquired this R factor may not show resistance until it has been exposed repeatedly to carbenicillin.     

The current MLVA typing scheme for <Emphasis Type="Italic">Enterococcus faecium</Emphasis> is less discriminatory than MLST and PFGE for epidemic-virulent,hospital-adapted clonal types

Background  

MLVA (multiple-locus variable-number tandem repeat analysis) is a reliable typing technique introduced recently to differentiate also isolates of Enterococcus faecium. We used the established VNTR (variable number of tandem repeats) scheme to test its suitability to differentiate 58 E. faecium isolates representing mainly outbreaks and clusters of infections and colonizations among patients from 31 German hospitals. All isolates were vancomycin-resistant (vanA type). Typing results for MLVA are compared with results of macrorestriction analysis in PFGE (pulsed-field gel electrophoresis) and MLST (multi-locus sequence typing).     

A Multidisciplinary Intervention to Reduce Infections of ESBL- and AmpC-Producing,Gram-Negative Bacteria at a University Hospital

In response to a considerable increase in the infections caused by ESBL/AmpC-producing Klebsiella pneumonia in 2008, a multidisciplinary intervention, with a main focus on antimicrobial stewardship, was carried out at one university hospital. Four other hospitals were used as controls. Stringent guidelines for antimicrobial treatment and prophylaxis were disseminated throughout the intervention hospital; cephalosporins were restricted for prophylaxis use only, fluoroquinolones for empiric use in septic shock only, and carbapenems were selected for penicillin-allergic patients, infections due to ESBL/AmpC-producing and other resistant bacteria, in addition to their use in severe sepsis/septic shock. Piperacillin-tazobactam ± gentamicin was recommended for empiric treatments of most febrile conditions. The intervention also included education and guidance on infection control, as well as various other surveillances. Two year follow-up data on the incidence rates of patients with selected bacterial infections, outcomes, and antibiotic consumption were assessed, employing before-and-after analysis and segmented regression analysis of interrupted time series, using the other hospitals as controls. The intervention led to a sustained change in antimicrobial consumption, and the incidence of patients infected with ESBL-producing K. pneumoniae decreased significantly (p<0.001). The incidences of other hospital-associated infections also declined (p’s<0.02), but piperacillin-tazobactam-resistant Pseudomonas aeruginosa and Enterococcus faecium infections increased (p’s<0.033). In wards with high antimicrobial consumption, the patient gut carrier rate of ESBL-producing bacteria significantly decreased (p = 0.023). The unadjusted, all-cause 30-day mortality rates of K. pneumoniae and E. coli were unchanged over the four-year period, with similar results in all five hospitals. Although not statistically significant, the 30-day mortality rate of patients with ESBL-producing K. pneumoniae decreased, from 35% in 2008–2009, to 17% in 2010–2011. The two-year follow-up data indicated that this multidisciplinary intervention led to a statistically significant decrease in the incidence of ESBL/AmpC-resistant K. pneumoniae infections, as well as in the incidences of other typical hospital-associated bacterial infections.     

Biotyping of Multidrug-Resistant Klebsiella pneumoniae Clinical Isolates from France and Algeria Using MALDI-TOF MS

Background

Klebsiella pneumoniae is one of the most important pathogens responsible for nosocomial outbreaks worldwide. Epidemiological analyses are useful in determining the extent of an outbreak and in elucidating the sources and the spread of infections. The aim of this study was to investigate the epidemiological spread of K. pneumoniae strains using a MALDI-TOF MS approach.

Methods

Five hundred and thirty-five strains of K. pneumoniae were collected between January 2008 and March 2011 from hospitals in France and Algeria and were identified using MALDI-TOF. Antibiotic resistance patterns were investigated. Clinical and epidemiological data were recorded in an Excel file, including clustering obtained from the MSP dendrogram, and were analyzed using PASW Statistics software.

Results

Antibiotic susceptibility and phenotypic tests of the 535 isolates showed the presence of six resistance profiles distributed unequally between the two countries. The MSP dendrogram revealed five distinct clusters according to an arbitrary cut-off at the distance level of 500. Data mining analysis of the five clusters showed that K. pneumoniae strains isolated in Algerian hospitals were significantly associated with respiratory infections and the ESBL phenotype, whereas those from French hospitals were significantly associated with urinary tract infections and the wild-type phenotype.

Conclusions

MALDI-TOF was found to be a promising tool to identify and differentiate between K. pneumoniae strains according to their phenotypic properties and their epidemiological distribution. This is the first time that MALDI-TOF has been used as a rapid tool for typing K. pneumoniae clinical isolates.     

Evaluation of a Mixing versus a Cycling Strategy of Antibiotic Use in Critically-Ill Medical Patients: Impact on Acquisition of Resistant Microorganisms and Clinical Outcomes

Objective

To compare the effect of two strategies of antibiotic use (mixing vs. cycling) on the acquisition of resistant microorganisms, infections and other clinical outcomes.

Methods

Prospective cohort study in an 8-bed intensive care unit during 35- months in which a mixing-cycling policy of antipseudomonal beta-lactams (meropenem, ceftazidime/piperacillin-tazobactam) and fluoroquinolones was operative. Nasopharyngeal and rectal swabs and respiratory secretions were obtained within 48h of admission and thrice weekly thereafter. Target microorganisms included methicillin-resistant S. aureus, vancomycin-resistant enterococci, third-generation cephalosporin-resistant Enterobacteriaceae and non-fermenters.

Results

A total of 409 (42%) patients were included in mixing and 560 (58%) in cycling. Exposure to ceftazidime/piperacillin-tazobactam and fluoroquinolones was significantly higher in mixing while exposure to meropenem was higher in cycling, although overall use of antipseudomonals was not significantly different (37.5/100 patient-days vs. 38.1/100 patient-days). There was a barely higher acquisition rate of microorganisms during mixing, but this difference lost its significance when the cases due to an exogenous Burkholderia cepacia outbreak were excluded (19.3% vs. 15.4%, OR 0.8, CI 0.5–1.1). Acquisition of Pseudomonas aeruginosa resistant to the intervention antibiotics or with multiple-drug resistance was similar. There were no significant differences between mixing and cycling in the proportion of patients acquiring any infection (16.6% vs. 14.5%, OR 0.9, CI 0.6–1.2), any infection due to target microorganisms (5.9% vs. 5.2%, OR 0.9, CI 0.5–1.5), length of stay (median 5 d for both groups) or mortality (13.9 vs. 14.3%, OR 1.03, CI 0.7–1.3).

Conclusions

A cycling strategy of antibiotic use with a 6-week cycle duration is similar to mixing in terms of acquisition of resistant microorganisms, infections, length of stay and mortality.     

Clusters of Toxoplasmosis in Ganghwa-gun,Cheorwon-gun,and Goseong-gun,Korea

We find out the clusters with high toxoplasmosis risk to discuss the geographical pattern in Gyodong-myeon and Samsan-myeon of Ganghwa-gun, Cheorwon-gun, and Goseong-gun, Korea. Seroepidemiological data of toxoplasmosis surveyed using rapid diagnostic tests for the residents in the areas in 2019 were analyzed to detect clusters of the infection. The cluster was investigated using the SaTScan program which is based on Kulldorff’s scan statistic. The clusters were found with P-values in each region analyzed in the program, and the risk and patient incidence of specific areas can be examined by the values such as relative risk and log likelihood ratio. Jiseok-ri and Insa-ri were found to be a cluster in Gyodong-myeon and Seokmo-ri was the cluster in Samsan-myeon. Yangji-ri and Igil-ri were found to be a cluster in Cheorwon-gun and Madal-ri and Baebong-ri were the cluster in Goseong-gun. This findings can be used to monitor and prevent toxoplasmosis infections occurring in vulnerable areas.     

Spatio-temporal analysis of infra-specific genetic variations among a Pseudomonas aeruginosa water network hospital population: invasion and selection of clonal complexes

Aims: To investigate infra-specific spatio-temporal dynamics of a hospital water network Pseudomonas aeruginosa population. To infer the origin of water network isolates and assess their potential health hazard. Methods and Results: 168 P. aeruginosa strains were isolated from tap waters and swabs of tap nozzle aerators of a hospital unit, over 2 years, and from rectal swabs and nosocomial infections. Genetic diversity among this collection was assessed by pulsed field gel electrophoresis of SpeI restricted genomic DNA. Virulence gene sets, biofilm properties, and hypochlorite resistance were analysed. Exactly 68% of the water samples and 74% of the tap nozzle aerators harboured P. aeruginosa. The strains were divided into 22 clonal lineages, with one dominant clone shown to have been involved in a nosocomial infection. Conclusions: An important turnover among the P. aeruginosa hospital population was observed. Some clonal lineages were found to persist, spread in the unit, and diversify into clonal complexes. Rectal carriage appeared an important source of contamination of the water network. Significance and Impact of the Study: High P. aeruginosa infra-specific population diversity suggested a broad ability in colonizing water networks but persistence analysis indicated a strong selection leading to the emergence of dominant clones.     

Mutational inactivation of OprD in carbapenem-resistant Pseudomonas aeruginosa isolates from Korean hospitals

This study investigated the mechanisms underlying the carbapenem resistance of bloodstream isolates of Pseudomonas aeruginosa obtained from two Korean hospitals. Of the 79 P. aeruginosa isolates, 22 and 21 were resistant to imipenem and meropenem, respectively. The 22 imipenem-resistant P. aeruginosa isolates were classified into 7 sequence types (STs) and 13 pulsotypes. Twelve imipenem-resistant isolates from one hospital were found to belong to the international clone ST111. Two imipenem-resistant P. aeruginosa ST235 isolates carried the bla _IMP-6 gene, but the remaining 20 isolates did not produce carbapenemases. Mutations in the oprD gene and a related decrease in gene expression were found in 21 and 5 isolates, respectively. However, all imipenemresistant P. aeruginosa isolates showed no significant expression of OprD in the outer membrane as compared with that of carbapenem-susceptible PAO1 strain. Overexpression of genes associated with efflux pumps, including mexB, mexD, mexF, and mexY, was not found in any imipenem-resistant isolate. One imipenem-resistant P. aeruginosa isolate overexpressed the ampC gene. Our results show that the low permeability of drugs due to the mutational inactivation of OprD is primarily responsible for carbapenem resistance in bloodstream isolates of P. aeruginosa from Korean hospitals.     

Surveillance and Correlation of Antimicrobial Usage and Resistance of Pseudomonas aeruginosa: A Hospital Population-Based Study

This retrospective study evaluated trends and association between resistance of Pseudomonas aeruginosa isolated from patients with hospital-acquired infections (HAIs) and hospital antimicrobial usage from 2003 through 2011 in a tertiary care hospital in northeast China. HAI was defined as occurrence of infection after hospital admission, without evidence that infection was present or incubating (≦48 h) on admission. In vitro susceptibilities were determined by disk diffusion test and susceptibility profiles were determined using zone diameter interpretive criteria, as recommended by Clinical and Laboratory Standards Institute (CLSI). Data on usage of various antimicrobial agents, expressed as defined daily dose (DDD) per 1,000 patients-days developed by WHO Anatomical Therapeutical Chemical (ATC)/DDD index 2011, were collected from hospital pharmacy computer database. Most of 747 strains of P. aeruginosa were collected from respiratory samples (201 isolates, 26.9%), blood (179, 24.0%), secretions and pus (145, 19.4%) over the years. Time series analysis demonstrated a significant increase in resistance rates of P. aeruginosa to ticarcillin/clavulanic acid, piperacillin/tazobactam, cefoperazone/sulbactam, piperacillin, imipenem, meropenem, ceftazidime, cefepime, ciprofloxacin, and levofloxacin except aminoglycosides over time in the hospital (P<0.001). The rates of carbapenem-resistant P. aeruginosa (CRPA) isolated from patients with HAIs were 14.3%, 17.1%, 21.1%, 24.6%, 37.0%, 48.8%, 56.4%, 51.2%, and 54.1% over time. A significant increase in usage of anti-pseudomonal carbapenems (P<0.001) was seen. ARIMA models demonstrated that anti-pseudomonal carbapenems usage was strongly correlated with the prevalence of imipenem and meropenem-resistant P. aeruginosa (P<0.001). Increasing of quarterly CRPA was strongly correlated at one time lag with quarterly use of anti-pseudomonal carbapenems (P<0.001). Our data demonstrated positive correlation between anti-pseudomonal antimicrobial usage and P. aeruginosa resistance to several classes of antibiotics, but not all antimicrobial agents in the hospital.     

Robustness and Plasticity of Metabolic Pathway Flux among Uropathogenic Isolates of Pseudomonas aeruginosa

Pseudomonas aeruginosa is a human pathogen that frequently causes urinary tract and catheter-associated urinary tract infections. Here, using ¹³C-metabolic flux analysis, we conducted quantitative analysis of metabolic fluxes in the model strain P. aeruginosa PAO1 and 17 clinical isolates. All P. aeruginosa strains catabolized glucose through the Entner-Doudoroff pathway with fully respiratory metabolism and no overflow. Together with other NADPH supplying reactions, this high-flux pathway provided by far more NADPH than needed for anabolism: a benefit for the pathogen to counteract oxidative stress imposed by the host. P. aeruginosa recruited the pentose phosphate pathway exclusively for biosynthesis. In contrast to glycolytic metabolism, which was conserved among all isolates, the flux through pyruvate metabolism, the tricarboxylic acid cycle, and the glyoxylate shunt was highly variable, likely caused by adaptive processes in individual strains during infection. This aspect of metabolism was niche-specific with respect to the corresponding flux because strains isolated from the urinary tract clustered separately from those originating from catheter-associated infections. Interestingly, most glucose-grown strains exhibited significant flux through the glyoxylate shunt. Projection into the theoretical flux space, which was computed using elementary flux-mode analysis, indicated that P. aeruginosa metabolism is optimized for efficient growth and exhibits significant potential for increasing NADPH supply to drive oxidative stress response.