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Current trends in the epidemiology of nosocomial bloodstream infections in patients with hematological malignancies and solid neoplasms in hospitals in the United States.

A total of 2340 patients with underlying malignancy were identified among 22,631 episodes of nosocomial bloodstream infections (BSIs) in a prospectively collected database for 49 hospitals in the United States (Surveillance and Control of Pathogens of Epidemiologic Importance [SCOPE] Project). Data were obtained for the period of March 1995 through February 2001. Gram-positive organisms accounted for 62% of all BSIs in 1995 and for 76% in 2000 (P<.001), and gram-negative organisms accounted for 22% and 14% of all BSIs for these years, respectively. Neutropenia was observed in 30% of patients, so neutropenic and nonneutropenic patients were compared. In both, the predominant pathogens were coagulase-negative staphylococci (32% of isolates recovered from neutropenic patients and 30% of isolates recovered from nonneutropenic patients). The source of BSI was not determined for 57% of patients. The crude mortality rate was 36% for neutropenic patients and 31% for nonneutropenic patients.

Adolescent↗

Quinolone resistance is associated with increased risk of invasive illness or death during infection with Salmonella serotype Typhimurium.

In a registry-based cohort study, we determined the risk of invasive illness or death associated with infection with quinolone-resistant Salmonella serotype Typhimurium. We linked data from the Danish surveillance registry of enteric pathogens with data from the Danish civil registration system and 2 national health registries. Of 1323 patients infected with Salmonella Typhimurium, 46 (3.5%) were hospitalized due an invasive illness within 90 days of infection, and 16 (1.2%) died within 90 days of infection. After adjustment for age, sex, and comorbidity, infection with quinolone-resistant Salmonella Typhimurium was associated with a 3.15-fold (95% confidence interval, 1.39-7.10-fold) higher risk of invasive illness or death within 90 days of infection, compared with that observed for infection with pansusceptible strains.

Anti-Bacterial Agents↗

Adverse health events associated with antimicrobial drug resistance in Campylobacter species: a registry-based cohort study.

BACKGROUND: Resistance to clinically important antimicrobial agents, particularly fluoroquinolones and macrolides, is increasing among Campylobacter isolates, but few studies have explored the human health consequences of such resistance. METHODS: In a registry-based cohort study, we determined the risk of invasive illness and death associated with infection with quinolone- and erythromycin-resistant Campylobacter strains, while adjusting for comorbidity. We linked data from the Danish Surveillance Registry for Enteric Pathogens with data from the Civil Registration System and National Health Registries. RESULTS: Of 3471 patients with Campylobacter infection, 22 (0.63%) had an adverse event, defined as invasive illness or death, within 90 days of the date of receipt of samples. Patients infected with quinolone-resistant Campylobacter strains had a 6-fold increased risk of an adverse event within 30 days of the date of receipt of samples, compared with patients infected with quinolone- and erythromycin-susceptible Campylobacter strains (adjusted odds ratio [AOR], 6.17 [95% confidence interval {CI}, 1.62-23.47]). However, infection with erythromycin-resistant strains was associated with a >5-fold risk of an adverse event within 90 days of the date of receipt of samples (AOR, 5.51 [95% CI, 1.19-25.50]). CONCLUSIONS: The present study provides evidence of the human health consequences of resistance to clinically important agents among Campylobacter infections and the need for increased efforts to mitigate such resistance.

Adult↗

Epidemiology of methicillin-susceptible Staphylococcus aureus in the neonatal intensive care unit.

OBJECTIVE: When the incidence of methicillin-susceptible Staphylococcus aureus (MSSA) infection or colonization increased in our neonatal intensive care unit (NICU), we sought to further our understanding of the relationship among colonization with MSSA, endemic infection, and clonal spread. DESIGN: A retrospective cohort study was used to determine risk factors for acquisition of a predominant clone of MSSA (clone "B"). SETTING: A 45-bed, university-affiliated, level III-IV NICU. PATIENTS: Infants hospitalized in the NICU from October 1999 to September 2000. INTERVENTIONS: Infection control strategies included surveillance cultures of infants, cohorting infected or colonized infants, contact precautions, universal glove use, mupirocin treatment of the anterior nares of all infants in the NICU, and a hexachlorophene bath for infants weighing 1,500 g or more. RESULTS: During the 1-year study period, three periods of increased incidence of MSSA colonization or infection, ranging from 6.4 to 13.5 cases per 1,000 patient-days per month, were observed. Molecular typing using pulsed-field gel electrophoresis demonstrated two predominant clones, clone "B" and clone "G," corresponding to two periods of increased incidence. Multivariate analysis demonstrated that length of stay (OR, 1.035; 95% confidence interval [CI95], 1.008 to 1.062; P = .010) increased risk per day) and the use of H2-blockers (OR, 20.44; CI95, 2.48 to 168.26; P = .005) were risk factors for either colonization or infection with clone "B," and that the use of peripheral catheters was protective (OR, 0.06; CI95, 0.01 to 0.43; P= .005). CONCLUSIONS: Control of MSSA represents unique challenges as colonization is expected, endemic infections are tolerated, and surveillance efforts generally focus on multidrug-resistant pathogens. Future studies should address cost-effective surveillance strategies for endemic infections.

Cohort Studies↗

Antibiotic susceptibility of Streptococcus pneumoniae isolates in Portugal. A multicenter study between 1989 and 1993.

A total of 1,104 strains of Streptococcus pneumoniae were isolated from hospitalized patients (75.5%) and from colonization sites at the Public Health Institute (24.5%) during the last 4 years (1989-1993). Penicillin resistance (defined as MIC > or = 0.1 microgram/liter) was found to increase in time: 4.6% in 1989, 4.9% in 1990, 6.4% in 1991, 11.3% in 1992, and 17% in 1993. In 1992, 0.8% of the strains had penicillin MIC = 2 mg/liter. Increase in penicillin resistance was also evident among invasive strains [blood, cerebrospinal fluid (CSF), pleura]: 2/92 isolates from 1989-1992 (2.3%) were penicillin resistant as compared to 7/101 isolates from 1992 (6.9%). Multiresistance (resistance to three or more antibiotics) was 4.4% with penicillin, tetracycline, chloramphenicol being the predominant resistant phenotype at the end of 1992. In 1993, strains with resistance to penicillin plus chloramphenicol plus tetracycline increased further. Erythromycin resistance was usually associated with clindamycin resistance, but the majority of such strains remained susceptible to penicillin. Drift in the direction of increasing MIC values was also noted during this 3-year period among "susceptible" isolates: bacteria with MIC of 6-10 ng/ml representing the majority of isolates in 1990-1991 decreased and were replaced by cells with MIC of 20 ng/ml. The most frequent pneumococcal serotypes were 23, 19, 3, 6, 14, 9, and 8, with the frequency of type 9 increasing from 2.9% (in 1989) through 3.2% (1990) to 6.4% (1992). Among all antibiotic resistant strains, the prevalent serotypes were 23, 9, 14, and 6. The chromosomal backgrounds of resistant isolates tested by pulsed-field gel electrophoresis showed close resemblance to the background of the serotype 23F multiresistant clone first identified in Spain. The data suggest that the recent large increase in the frequency of penicillin-resistant pneumococci represents the import of this clone into Portugal during the early 1990s. The increased frequency of drug-resistant pneumococci highlights the importance of continued surveillance of these dangerous pathogens.

Drug Resistance, Microbial↗

Automated identification of multiple micro-organisms from resequencing DNA microarrays.

There is an increasing recognition that detailed nucleic acid sequence information will be useful and even required in the diagnosis, treatment and surveillance of many significant pathogens. Because generating detailed information about pathogens leads to significantly larger amounts of data, it is necessary to develop automated analysis methods to reduce analysis time and to standardize identification criteria. This is especially important for multiple pathogen assays designed to reduce assay time and costs. In this paper, we present a successful algorithm for detecting pathogens and reporting the maximum level of detail possible using multi-pathogen resequencing microarrays. The algorithm filters the sequence of base calls from the microarray and finds entries in genetic databases that most closely match. Taxonomic databases are then used to relate these entries to each other so that the microorganism can be identified. Although developed using a resequencing microarray, the approach is applicable to any assay method that produces base call sequence information. The success and continued development of this approach means that a non-expert can now perform unassisted analysis of the results obtained from partial sequence data.

Algorithms↗

Does the cell wall skeleton from Bacille Calmette-Guérin directly induce interferon-gamma, independent of interleukin-12?

Interleukin-12 (IL-12), known to be a strong inducer of interferon-gamma (IFN-gamma), plays a vital role in activating the immune surveillance system against intracellular pathogens and malignant tumors. The authors have found that cancer patients showing marked IFN-gamma induction after inoculation with BCG-CWS (the cell wall skeleton from Bacille Calmette-Guérin) have a good prognosis. The present study was undertaken to determine whether the level of IL-12 is increased prior to, or along with, IFN-gamma induction in the serum of patients inoculated with BCG-CWS. Unexpectedly, we found no detectable amount of IL-12 in the serum throughout the entire time course. This suggests that a novel IFN-gamma inducing factor (IGIF) or another unknown IFN-gamma inducer may be working in place of IL-12 in the BCG-CWS system.

Adjuvants, Immunologic↗

Activation of neutrophil leukocytes: chemoattractant receptors and respiratory burst.

The human organism survives the constant attack by bacteria and other pathogens thanks to the surveillance function of the neutrophil leukocytes. At sites of infection, several messenger molecules are generated that attract neutrophils from the blood and direct their migration toward the microbes, a process termed chemotaxis. Neutrophils sense chemotactic agonists through a group of closely related, GTP-binding protein-coupled receptors. Several of these have been recently cloned and shown to belong to the superfamily of rhodopsin-like, seven-transmembrane-domain receptors. At the site of infection, the neutrophils engulf and kill the invading microbes. This critical function depends on the production of superoxide and related radicals by a tightly regulated, membrane-bound NADPH oxidase that is activated by chemotactic agonists and other inflammatory stimuli. The characteristics of the receptors as well as new insights into the mechanism of activation of the superoxide-forming oxidase as presented at a recent FASEB meeting symposium are reviewed.

Animals↗

Epidemiology of meningococcal disease in England and Wales 1993/94 to 2003/04: contribution and experiences of the Meningococcal Reference Unit.

The laboratory confirmation of meningococcal disease and characterization of Neisseria meningitidis isolates was improved considerably in England and Wales by the Meningococcal Reference Unit between epidemiological years 1993/94 and 2003/04 to meet the challenge of increasing numbers of cases of clinical disease and the requirement for enhanced surveillance. Improved case ascertainment was made possible by the rapid introduction of an innovative centralized reference service for non-culture PCR-based DNA detection of meningococci utilizing the ctrA and siaD PCR assays, complemented by consistent phenotypic characterization of submitted isolates from culture-proven cases. This allowed the increased prevalence of serogroup C disease in specific age groups and the apparent associated increase in mortality from 1995/96 to 1999/00 to be defined, thereby prompting accelerated intervention with the newly licensed meningococcal serogroup C conjugate (MCC) vaccines into the under-25-year UK population (in November 1999). The continued increase in and predominance of serogroup B cases (1993/94 to 2000/01) were observed in conjunction with their diverse and changing phenotypic characteristics. Trends observed to be associated with the predominant phenotypic combinations of serogroup, serotype and sero-subtype were: a decline of both C : 2b and B : 2b meningococci, and a decline of B : 15 : P1.7,16 with a concomitant increase of B : 4 : P1.4 over the 11-year period. Detailed routine surveillance rapidly confirmed the introduction of W135 : 2a : P1.5,2 meningococci into the UK during 2000 and 2001. The importance of continued detailed surveillance of this important pathogen cannot be overestimated, both to monitor the effectiveness of the MCC vaccine and to identify changes within the meningococcal population that can inform the design of anti-serogroup B vaccines.

Adolescent↗

Detection of free and plankton-associated Helicobacter pylori in seawater.

AIMS: To detect both free and plankton-associated Helicobacter pylori in seawater samples collected on the Italian coast of the Adriatic Sea using a nested-PCR. METHODS AND RESULTS: Dissolved oxygen, pH, salinity and chlorophyll 'a' were the parameters recorded together with the characterization of zooplanktonic organisms. Plankton-associated H. pylori DNA was searched for in water samples filtered through 200 and 64 microm nylon nets whereas free bacteria were retained with the subsequent filtration through 0.22 microm pore-size membranes. Nested-PCR using primers for the glmM (ureC) gene was performed to reveal the presence of H. pylori. The DNA sequencing of amplified products confirmed the specificity of the assay. The sensitivity of the nested-PCR assay for H. pylori detection was 62 CFU per 100 ml in spiked water samples. Helicobacter pylori either free or bound to planktonic organisms was found in seven of 12 monthly samples. In particular, free bacteria were detected during the summer sampling and in November, December and March associated to planktonic cells. CONCLUSIONS: The presence of free and plankton-associated H. pylori in seawater suggests that it can be a significant reservoir and a potential route of transmission for the microorganism. SIGNIFICANCE AND IMPACT OF THE STUDY: Our study seems to provide a promising background to define new and effective strategies for surveillance of this human pathogen.

Animals↗

Epidemiology and treatment of community-associated methicillin-resistant Staphylococcus aureus in children.

Similar to the epidemiology of methicillin-sensitive Staphylococcus aureus, community-associated methicillin-resistant S. aureus infections occur in children in different regions of the USA and throughout the world. Although minor skin and soft-tissue infections predominate, life-threatening invasive disease and death can result. The novel genetic elements, staphylococcal cassette chromosome mec IV and V, explain the narrow antibiotic resistance pattern, and suggest the mechanism of spread among staphylococci. Panton-Valentine leukocidin apparently plays a role in its pathogenesis. Clindamycin therapy is often effective for treatment, but inducible resistance can develop if the isolate exhibits macrolide resistance due to the erm mechanism. Other drugs displaying in vitro activity against community-associated methicillin-resistant S. aureus include trimethoprim-sulfamethoxazole, tetracyclines, quinolones, linezolid and vancomycin. While experience in pediatric patients is limited, daptomycin, ketolides, glycylcyclines, newer glycopeptides and beta-lactamase-stable cephalosporins may be useful in the future. Further research could include well-designed studies of mechanisms of virulence, continued surveillance of changes in pathogenicity and susceptibility, as well as treatment effectiveness.

Anti-Bacterial Agents↗

Excess mortality associated with antimicrobial drug-resistant Salmonella typhimurium.

In a matched cohort study, we determined the death rates associated with drug resistance in Salmonella Typhimurium. We linked data from the Danish Surveillance Registry for Enteric Pathogens with the Civil Registration System and the Danish National Discharge Registry. By survival analysis, the 2-year death rates were compared with a matched sample of the general Danish population, after the data were adjusted for differences in comorbidity. In 2,047 patients with S. Typhimurium, 59 deaths were identified. Patients with pansusceptible strains of S. Typhimurium were 2.3 times more likely to die 2 years after infection than persons in the general Danish population. Patients infected with strains resistant to ampicillin, chloramphenicol, streptomycin, sulfonamide, and tetracycline were 4.8 times (95% CI 2.2 to 10.2) more likely to die, whereas quinolone resistance was associated with a mortality rate 10.3 times higher than the general population.

Adolescent↗

Epithelial inflammation is associated with CCL28 production and the recruitment of regulatory T cells expressing CCR10.

Mucosal tissues require constant immune surveillance to clear harmful pathogens while maintaining tolerance to self Ags. Regulatory T cells (Tregs) play a central role in this process and expression of alpha(E)beta(7) has been reported to define a subset of Tregs with tropism for inflamed tissues. However, the signals responsible for recruiting Tregs to epithelial surfaces are poorly understood. We have isolated a subset of CCR10-expressing CD25+CD4+Foxp3+ Tregs with potent anti-inflammatory properties from chronically inflamed human liver. The CCR10+ Tregs were detected around bile ducts that expressed increased levels of the CCR10 ligand CCL28. CCL28 was secreted by primary human cholangiocytes in vitro in response to LPS, IL-1beta, or bile acids. Exposure of CCR10+ Tregs to CCL28 in vitro stimulated migration and adhesion to mucosal addressin cell adhesion molecule-1 and VCAM-1. Liver-derived CCR10+ Tregs expressed low levels of CCR7 but high levels of CXCR3, a chemokine receptor associated with infiltration into inflamed tissue and contained a subset of alpha(E)beta7(+) cells. We propose that CXCR3 promotes the recruitment of Tregs to inflamed tissues and CCR10 allows them to respond to CCL28 secreted by epithelial cells resulting in the accumulation of CCR10+ Tregs at mucosal surfaces.

Bile Ducts↗

[Changes of antimicrobial resistance among nonfermenting gram-negative bacilli isolated from intensive care units from 1994 to 2001 in China].

OBJECTIVE: To investigate the antimicrobial resistance among nonfermenting gram-negative bacilli isolated from intensive care units (ICUs) during the past 7 years in China. METHODS: From 1994 to 2001, the minimal inhibitory concentrations (MICs) of imipenem and other ten antibiotics for 4450 strains of nosocomial nonfermenting bacteria isolated from the ICUs of 32 hospitals in China were determined by E test. WHONET-5 software was used to analyze the data. RESULTS: The most predominant pathogens were Pseudomonas aeruginosa (46.9%), Acinetobacter spp. (31.0%), and Stenotrophomonas maltophilia (9.2%). The susceptibility rates of these nonfermenting gram-negative bacilli to cefoperazone/sulbactam, imipenem, ceftazidime, piperacillin/tazobactam, amikacin, cefepime, and ciprofloxacin were 78.6%, 77.0%, 70.1%, 69.5%, 69.9%, 63.0%, and 59.1% respectively. Imipenem and cefoperazone/sulbactam were the most active agents against nonfermenting bacilli other than S.maltophilia and Burkholderia cepacia with susceptible rates 84.2% and 77.4% respectively. From 1994 to 2001, the activity of these 11 antibiotics against Pseudomonas aeruginosa decreased; the susceptibility rates of the nonfermenting gram-negative bacilli to imipenem, ceftazidime, amikacin, cefoperazone/sulbactam, cefepime, and piperacillin/tazobactam ranged from 70.0% to 83.0%. The susceptibility rate of Acinetobacter spp. to imipenem was 95.0% and remained unchanged for years. The susceptibility rate to cefoperazone/sulbactam came second, however, it was decreased from 88.0% in 1996 to 69.0% in 2001. The susceptibility rates to ceftazidime, cefepime, piperacillin/tazobactam, ticarcillin/clavulanic acid, gentamicin, and ciprofloxacin ranged from 45% to 58%. The susceptibility of Stenotrophomonas maltophilia was the highest to cefoperazone/sulbactam, ceftazidime, and ticarcillin/clavulanic acid (78% approximately 85%). Cefoperazone/sulbactam, piperacillin/tazobactam, and imipenem inhibited 80% of Alcaligenes spp. Only cefoperazone/sulbactam and piperacillin/tazobactam inhibited 70% of the strains of Flavobacterium spp; and 73% approximately 86% of Burkholderia cepacia were susceptible to cefoperazone/sulbactam, piperacillin/tazobactam, ceftazidime, and cefepime. CONCLUSION: In recent 7 years, the antimicrobial resistance among nonfermenting gram-negative bacilli has increased in China. Antibiotics policy is urgently needed in order to delay the resistance development.

Anti-Bacterial Agents↗

Antibiotic resistance in 1962 invasive isolates of Escherichia coli in 27 Spanish hospitals participating in the European Antimicrobial Resistance Surveillance System (2001).

In Europe, antimicrobial resistance of invasive pathogens has been monitored since 1998 by the European Antimicrobial Resistance Surveillance System (EARSS). The goal of this study is to analyse the susceptibility data of invasive Escherichia coli collected by 27 Spanish laboratories in 2001. Each laboratory identified strains and tested their susceptibility using its own methods. To assess the comparability of susceptibility test results, a quality assurance exercise was performed. We report data from 1962 invasive isolates of E. coli: 1959 from blood and three from cerebrospinal fluid, corresponding to the same number of patients. Resistance to ampicillin, co-trimoxazole, ciprofloxacin and gentamicin was found in 58.46%, 32.91%, 17.19% and 6.39% of isolates, respectively. Extended-spectrum beta-lactamase (ESBL) production was detected in 30 strains (1.55%). Ciprofloxacin resistance was higher in isolates from men and in-patients than in those from women and out-patients (P < 0.001). Resistance to ampicillin and co-trimoxazole was more widespread in children than in adults: 70.37% versus 57.87% (P = 0.01) and 41.84% versus 32.53% (P = 0.05). Non-significant differences in resistance to fluoroquinolones were observed between isolates from children (11.1%) and adults (17.54%), despite the fact that fluoroquinolones are not administered to children. Significantly, resistance to non-beta-lactam antibiotics (co-trimoxazole, ciprofloxacin and gentamicin) was more prevalent in ampicillin-resistant strains and ESBL-producing strains than in ampicillin-susceptible strains and non-ESBL-producing strains. Multidrug resistance was present in 13.92% of isolates; the most prevalent phenotype was resistance to ampicillin, co-trimoxazole and ciprofloxacin, which was detected in 59.36% of multiresistant strains and in 8.22% of strains overall.

Adult↗

The analysis of hospital infection data using hidden Markov models.

Surveillance data for communicable nosocomial pathogens usually consist of short time series of low-numbered counts of infected patients. These often show overdispersion and autocorrelation. To date, almost all analyses of such data have ignored the communicable nature of the organisms and have used methods appropriate only for independent outcomes. Inferences that depend on such analyses cannot be considered reliable when patient-to-patient transmission is important. We propose a new method for analysing these data based on a mechanistic model of the epidemic process. Since important nosocomial pathogens are often carried asymptomatically with overt infection developing in only a proportion of patients, the epidemic process is usually only partially observed by routine surveillance data. We therefore develop a 'structured' hidden Markov model where the underlying Markov chain is generated by a simple transmission model. We apply both structured and standard (unstructured) hidden Markov models to time series for three important pathogens. We find that both methods can offer marked improvements over currently used approaches when nosocomial spread is important. Compared to the standard hidden Markov model, the new approach is more parsimonious, is more biologically plausible, and allows key epidemiological parameters to be estimated.

Cross Infection↗

Nasopharyngeal pathogens in children with acute otitis media in a low-antibiotic use country.

OBJECTIVE: Acute otitis media (AOM) is one of the most common diseases of childhood. Knowledge, of which bacteria are the most common pathogens in AOM and their susceptibilities towards antibiotics, is essential for the reasonable empiric treatment. With rapidly increasing frequencies of antibiotic resistance surveillance of the common etiologic pathogens has become pertinent. The purpose of this paper is to present the bacteriological findings and antibiotic susceptibilities, in cultures from nasopharyngeal swabs, in Danish children with AOM. METHODS: Children aged up to 10 years who had AOM diagnosed in general practice in Denmark were swabbed in nasopharynx, cultures were incubated and susceptibility testing was performed as tablet diffusion and minimal inhibitory concentrations (MICs) were determined by E-test. RESULTS: We included 331 patients, in 257 bacteria were found, which could be classified as commonly ear pathogenic. The most frequent bacteria found was Streptococcus pneumoniae followed by Haemophilus influenzae and Moraxella catarrhalis. Ninety-six percent of the tested S. pneumoniae were susceptible towards penicillin and 99% towards erythromycin. Eighty-nine percent of the H. influenzae were susceptible to ampicillin and all tested M. catarrhalis were susceptible towards erythromycin. In more than 30% of H. influenzae MIC of phenoxymethylpenicillin were above the level that could be achieved in middle ear fluid. CONCLUSION: Antimicrobial resistance is still infrequent in pathogens that might cause AOM in children in Denmark; this is probably due to minimal use of antibiotics as well as the use of phenoxymethylpenicillin as primary drug for treatment of AOM. Phenoxymethylpenicillin and azithromycin are not efficient for treating the majority of infections due to H. influenzae.

Acute Disease↗

The Enter-net and Salm-gene databases of foodborne bacterial pathogens that cause human infections in Europe and beyond: an international collaboration in surveillance and the development of intervention strategies.

The free movement of people and foodstuffs between countries are effective ways of distributing disease internationally. There is a requirement for a mechanism whereby data and information on potential outbreaks of foodborne pathogens can be disseminated rapidly to those who need to know. The Enter-net dedicated surveillance network provides this mechanism, complemented by the Salm-gene molecular typing network. Data on epidemiological and microbiological features on current cases, as well as background levels of infections are immediately available within the Enter-net databases. The Salm-gene network with its database of harmonized salmonella PFGE patterns from the participating European countries provides immediate, and electronically exchangeable, DNA fingerprints of outbreak strains. This prompt electronic dissemination of information regarding unusual events with international implications ensures that public health interventions can be implemented and cases of foodborne disease prevented.

Animals↗