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Respiratory pathogens: assessing resistance patterns in Europe and the potential role of grepafloxacin as treatment of patients with infections caused by these organisms.

Although most respiratory tract infections (RTI) are caused by viruses, various bacteria, particularly Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis, are common causes of community-acquired pneumonia, acute exacerbations of chronic bronchitis, otitis media and sinusitis. Empirical antibiotic therapy of patients with RTI must take account of the increasing prevalence of resistance among the predominant pathogens. Europe-wide susceptibility surveillance studies have revealed that resistance to penicillin and macrolides is highly prevalent among isolates of S. pneumoniae from France and Spain. Uniquely, in Italy, macrolide resistance is highly prevalent while the prevalence of penicillin resistance is low. Resistance to other antibiotic classes, including chloramphenicol, doxycycline and, in particular, co-trimoxazole, is associated with penicillin resistance in pneumococci, but resistance to the fluoroquinolones is rare. beta-Lactamase production is the principal mechanism of resistance in isolates of H. influenzae and M. catarrhalis, with fluoroquinolone resistance being detected rarely in these pathogens. In 1998 a surveillance study involving 15 European countries determined the susceptibilities of many respiratory pathogens to a range of antimicrobials, including grepafloxacin. The MIC(90) of grepafloxacin for 1251 isolates of S. pneumoniae was 0.25 mg/L, the MICs for only five strains being >2 mg/L, and 99.4% of all of the isolates tested were inhibited by concentrations </=0.5 mg/L. The MIC(90)s of grepafloxacin for 587 isolates of H. influenzae and 323 of Haemophilus parainfluenzae were 0.015 and 0.06 mg/L, respectively, while that for 509 isolates of M. catarrhalis was 0.03 mg/L. The MIC(90)s for 1164 isolates of methicillin-susceptible Staphylococcus aureus and 435 isolates of Klebsiella pneumoniae were 0.12 and 0.25 mg/L, respectively. Other studies have shown grepafloxacin to be highly active against clinical isolates of Legionella pneumophila (MIC(90) 0.015 mg/L), Mycoplasma pneumoniae (MIC(90) 0.5 mg/L) and Chlamydia pneumoniae (MICs 0.06-0.12 mg/L). Current susceptibility data indicate that fluoroquinolone resistance rates among bacterial respiratory tract pathogens are low in European countries. The enhanced potency and activity of grepafloxacin against isolates of S. pneumoniae, including those exhibiting resistance to unrelated classes of antibiotics, together with its activity against other respiratory tract pathogens, suggest that this drug has considerable potential as empirical therapy of patients with a wide range of RTI.

Anti-Infective Agents↗

Whole-genome sequencing-based pathogen characterization for streptococcal infection directly from positive blood culture samples.

Clinical laboratories are increasingly using diagnostic tests directly on positive blood cultures, which may lead to fewer attempts to recover bacterial isolates. Consequently, public health laboratories can benefit from assays that directly process blood culture samples without requiring submission of clinical isolates to determine additional pathogen features not identified by clinical tests, such as vaccine serotype and bacterial genomic relatedness, for surveillance and outbreak response purposes. In partnership with the Minnesota Active Bacterial Core surveillance (ABCs) site, we identified blood culture samples positive for ABCs streptococcal pathogens and characterized them by a direct whole-genome sequencing from blood culture (dWGS) assay. The dWGS results were compared with the results of a reference method (WGS of isolates from the same cultures) to evaluate concordance in pathogen features and genome assemblies. Of the 97 eligible blood culture samples, 83 (86%) passed dWGS quality control criteria and were subjected to a total of 655 dWGS-based tests, which yielded 651 (99.3%) evaluable results. The percent agreement with reference results was 100% (83/83) for M protein gene (emm)/capsular types and 100% (81/81) for multilocus sequencing types. For genotypic antimicrobial susceptibility testing prediction, the percent prediction agreement was 100% (487/487), false resistant prediction rate was 0% (0/417), and the false susceptible prediction rate was 0% (0/66). Assemblies of pathogen genomes from the same patient differed by 1.08 &#xb1; 1.68 (mean &#xb1; SD) sites per genome. The dWGS assay can extract high-quality, important streptococcal strain characteristics directly from positive blood culture samples to support evolving public health needs.IMPORTANCEWhole-genome sequencing (WGS) technologies have emerged as a transformative toolkit used by public health microbiology laboratories to detect and characterize pathogens. The surveillance of bacterial diseases often relies on clinical laboratories to submit pathogen isolates to regional or national public health laboratories, which have the capacity to routinely conduct WGS-based strain characterization. Clinical laboratories are increasingly using diagnostic tests directly on positive blood cultures, which may lead to fewer attempts to recover bacterial isolates. The study evaluated a direct whole-genome sequencing from blood culture (dWGS) assay that directly processes blood culture samples. The dWGS assay recovered high quality, important streptococcal strain characteristics, including vaccine serotypes and whole-genome assemblies, without requiring submission of clinical isolates. Thus, the dWGS assay represents a promising tool for addressing the evolving needs of public health laboratories in the metagenomics era.

Humans↗

Antimicrobial drug resistance in pathogens causing nosocomial infections at a university hospital in Taiwan, 1981-1999.

To determine the distribution and antimicrobial drug resistance in bacterial pathogens causing nosocomial infections, surveillance data on nosocomial infections documented from 1981 to 1999 at National Taiwan University Hospital were analyzed. During this period, 35,580 bacterial pathogens causing nosocomial infections were identified. Candida species increased considerably, ranking first by 1999 in the incidence of pathogens causing all nosocomial infections, followed by Staphylococcus aureus and Pseudomonas aeruginosa. Candida species also increased in importance as bloodstream infection isolates, from 1.0% in 1981-1986 to 16.2% in 1999. The most frequent isolates from urinary tract infections were Candida species (23.6%), followed by Escherichia coli (18.6%) and P. aeruginosa (11.0%). P. aeruginosa remained the most frequent isolates for respiratory tract and surgical site infections in the past 13 years. A remarkable increase in incidence was found in methicillin-resistant S. aureus (from 4.3% in 1981-1986 to 58.9% in 1993-1998), cefotaxime-resistant E. coli (from 0% in 1981-1986 to 6.1% in 1993-1998), and cefotaxime-resistant Klebsiella pneumoniae (from 4.0% in 1981-1986 to 25.8% in 1993-1998). Etiologic shifts in nosocomial infections and an upsurge of antimicrobial resistance among these pathogens, particularly those isolated from intensive care units, are impressive and alarming.

Anti-Bacterial Agents↗

Rapid identification of emerging pathogens: coronavirus.

We describe a new approach for infectious disease surveillance that facilitates rapid identification of known and emerging pathogens. The process uses broad-range polymerase chain reaction (PCR) to amplify nucleic acid targets from large groupings of organisms, electrospray ionization mass spectrometry for accurate mass measurements of PCR products, and base composition signature analysis to identify organisms in a sample. We demonstrate this principle by using 14 isolates of 9 diverse Coronavirus spp., including the severe acute respiratory syndrome-associated coronavirus (SARS-CoV). We show that this method could identify and distinguish between SARS and other known CoV, including the human CoV 229E and OC43, individually and in a mixture of all 3 human viruses. The sensitivity of detection, measured by using titered SARS-CoV spiked into human serum, was approximate, equals1 PFU/mL. This approach, applicable to the surveillance of bacterial, viral, fungal, or protozoal pathogens, is capable of automated analysis of >900 PCR reactions per day.

Animals↗

[Excess mortality associated with antibiotic resistant Salmonella typhimurium].

INTRODUCTION: The use of antimicrobials in food production has been associated with drug-resistance in foodborne pathogens such as Salmonella and Campylobacter. However, little is known about the health impact of antimicrobial drug-resistance in these pathogens. In a matched cohort study, we determined the mortality associated with drug-resistance in Salmonella Typhimurium. MATERIAL AND METHODS: Data from the Danish Surveillance Registry for Enteric Pathogens were linked with the Civil Registration System and the Danish National Patient Registry. By survival analysis, the two-year mortality among patients was compared with a matched sample of the general Danish population adjusted for differences in comorbidity. RESULTS: Among 2047 cases of S. Typhimurium, 59 deaths were identified. Patients with pan-susceptible strains of S. Typhimurium were 2.3 times (95 per cent confidence interval [CI] 1.5-3.5) more likely to die in the two-year follow-up period 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 per cent CI 2.2-10.5) more likely to die, whereas quinolone-resistance was associated with a 10.3 times (95 percent CI 2.8-37.8) higher mortality than the general population. DISCUSSION: Overall, infections with S. Typhimurium were associated with excess mortality. Patients infected with multi-drug resistant strains had a tendency towards higher mortality than patients infected with non-multiresistant strains. Particular risk was associated with quinolone-resistance in foodborne S. Typhimurium, and the excess mortality among patients infected with multi-drug resistant S. Typhimurium could be attributed to additional quinolone resistance in many of the multi-drug resistant isolates.

4-Quinolones↗

Pathogens: raft hijackers.

Throughout evolution, organisms have developed immune-surveillance networks to protect themselves from potential pathogens. At the cellular level, the signalling events that regulate these defensive responses take place in membrane rafts--dynamic microdomains that are enriched in cholesterol and glycosphingolipids--that facilitate many protein-protein and lipid-protein interactions at the cell surface. Pathogens have evolved many strategies to ensure their own survival and to evade the host immune system, in some cases by hijacking rafts. However, understanding the means by which pathogens exploit rafts might lead to new therapeutic strategies to prevent or alleviate certain infectious diseases, such as those caused by HIV-1 or Ebola virus.

Animals↗

[Drug-resistant bacteria in clinical situations].

There are two major categories of drug-resistant bacteria that can cause severe and intractable infections. The first includes multi drug-resistant Mycobacterium tuberculosis(MDRMT), penicillin-resistant Streptococcus pneumoniae(PRSP), and beta-lactamase positive or negative ampicillin-resistant Haemophilus influenzae, which used to be isolated from the patients with community-acquired infection. However, these pathogens have been often isolated in recent years from patients with hospital/chronic care facilities/nursing-home mass infection. The second major category includes methicillin-resistant Staphylococcus aureus(MRSA), vancomycin-resistant Enterococcus species(VRE), Pseudomonas aeruginosa, and Enterobacteriaceae including extended-spectrum beta-lactamases(ESBLs) producing strain, which are mainly isolated from compromised patients with nosocomial infections. The pathogenicity of these pathogens, almost all of which are found in the normal flora of humans, is weak, but often cause nosocomial infections in compromised patients. We need, therefore, surveillance system for these pathogens, and carefully determine whether these pathogens, if isolated, are causative pathogens.

Bacteria↗

The state of infection surveillance and control in Canadian acute care hospitals.

BACKGROUND: Nosocomial infections and antibiotic-resistant pathogens cause significant morbidity, mortality, and economic costs. The infection surveillance and control resources and activities in Canadian acute care hospitals had not been assessed in 20 years. METHODS: In 2000, surveys were mailed to infection control programs in all Canadian hospitals with more than 80 acute care beds. The survey was modeled after the US Study on the Efficacy of Nosocomial Infection Control instrument, with new items dealing with resistant pathogens and computerization. Surveillance and control indices were calculated. RESULTS: One hundred seventy-two of 238 (72.3%) hospitals responded. In 42.1% of hospitals, there was fewer than 1 infection control practitioner per 250 beds. Just 60% of infection control programs had physicians or doctoral professionals with infection control training who provided services. The median surveillance index was 65.6/100, and the median control index was 60.5/100. Surgical site infection rates were reported to individual surgeons in only 36.8% of hospitals. CONCLUSIONS: There were deficits in the identified components of effective infection control programs. Greater investment in resources is needed to meet recommended standards and thereby reduce morbidity, mortality, and expense associated with nosocomial infections and antibiotic-resistant pathogens.

Acute Disease↗

Multidrug-resistant enterococci: a threat to the surgical patient.

The enterococcus has become an important nosocomial pathogen, reported by the National Nosocomial Infections Surveillance System as the third most common pathogen associated with blood-stream infections and the second most commonly isolated pathogen overall. It is now more frequently recognized as a cause of superinfection in the surgical patient, as the possible result of the frequent use of ineffective antimicrobials for prophylaxis and treatment. Both of these findings are due, in part, to the intrinsic antimicrobial resistance of the enterococci. Of greater concern is the ready ability of this organism to acquire resistance traits. During the past 5 years, the appearance and rapid dissemination of strains with high-level resistance to vancomycin, ampicillin, gentamicin, and streptomycin have been reported; in some cases, no effective antimicrobial therapy was available to patients infected with these strains. Enterococci, in addition to their intrinsic and acquired tolerance to beta-lactams, have acquired the ability to inactivate penicillin and ampicillin via beta-lactamase production. Prompt recognition of such multiresistant enterococci, the implementation of effective infection control precautions, and rational use of antimicrobials may limit or even prevent the spread of such strains in the hospital setting.

Anti-Bacterial Agents↗

Antimicrobial susceptibility of the pathogens of bacteraemia in the UK and Ireland 2001-2002: the BSAC Bacteraemia Resistance Surveillance Programme.

OBJECTIVES: To describe the current patterns of antimicrobial resistance in the major pathogens of bacteraemia in the UK and Ireland, to highlight any unexpected resistance patterns and to act as a reference baseline for future studies. METHODS: In 2001 and 2002, 5092 blood culture isolates were collected by 29 laboratories distributed across the UK and Ireland. A single central laboratory re-identified the isolates and measured MICs by the BSAC agar dilution method. RESULTS: Oxacillin resistance was found in 42% of Staphylococcus aureus and 76% of coagulase-negative staphylococci. Streptococci were generally susceptible to beta-lactams, but tetracycline resistance was common (except in Streptococcus pneumoniae) and particularly common among group B isolates (82% resistant). Nine percent of S. pneumoniae had reduced susceptibility to penicillin (MICs 0.12-1 mg/L), but none required >/=2 mg/L for inhibition. High-level gentamicin resistance was seen in 43% of Enterococcus faecalis, often in combination with raised ciprofloxacin MICs (>/=32 mg/L), but these isolates remained susceptible to ampicillin and imipenem. Only linezolid and tigecycline showed in vitro potency against a large proportion of Enterococcus faecium. Vancomycin resistance was restricted to enterococci (20% of E. faecium, 3% of E. faecalis) and a single isolate of coagulase-negative staphylococci (0.2%, MIC of 8 mg/L). Escherichia coli isolates were commonly resistant to amoxicillin (56%) and tetracycline (88%) but remained susceptible to ceftazidime, piperacillin/tazobactam and imipenem. Extended-spectrum beta-lactamases were detected in 2% of E. coli (none in 2001, 3.2% in 2002), 5% of Klebsiella spp. and 8% of Enterobacter spp. Resistance rates of Pseudomonas aeruginosa to ciprofloxacin, ceftazidime, gentamicin, imipenem and piperacillin/tazobactam were between 4% and 7%. Among the newly licensed and developmental agents, there was no resistance to linezolid in Gram-positive organisms. Ertapenem had a wide spectrum, covering Enterobacteriaceae, streptococci and oxacillin-susceptible staphylococci. MICs of tigecycline were low for Gram-positive species and Enterobacteriaceae except Proteeae and Enterobacter spp. CONCLUSION: Antimicrobial resistance among major bloodstream pathogens to those antimicrobials often selected for empirical therapy was relatively uncommon in 2001-2002, usually <10%. An important exception was oxacillin resistance in S. aureus.

Adult↗

Methods for cost-efficient, whole genome sequencing surveillance for enhanced detection of outbreaks in a hospital setting.

INTRODUCTION: Outbreaks of healthcare-associated infections (HAI) result in substantial patient morbidity and mortality; mitigation efforts by infection prevention teams have the potential to curb outbreaks and prevent transmission to additional patients. The incorporation of whole genome sequencing (WGS) surveillance of suspected high-risk pathogens often identifies outbreaks that are not detected by traditional infection prevention methods and provides evidence for transmission. Our approach to real-time WGS surveillance, the Enhanced Detection System for Healthcare-Associated Transmission (EDS-HAT), has 1) identified serious outbreaks that were otherwise undetected and 2) shown the potential to be cost saving. METHODS: We describe our cost-efficient methods to perform WGS surveillance and data analysis of pathogens for institutions that are interested in expanding infection prevention surveillance. We provide an overview of the weekly workflow of EDS-HAT during two distinct phases over three years. RESULTS: In an average week at our tertiary healthcare system, we sequenced 60 samples at a cost of less than $100 each during Phase 1, and 80 samples for less than $70 each in Phase 2, inclusive of laboratory reagents and staff salaries. The average turnaround time, from sample collection to reporting data to infection prevention, was nine days. CONCLUSIONS: Performing EDS-HAT in real-time can be both feasible and time-efficient. Providing such timely information to aid in outbreak detection could identify transmission events sooner and thus could increase patient safety.

Disease Outbreaks↗

Antimicrobial resistance among isolates of respiratory tract infection pathogens from the southern United States: data from the PROTEKT US surveillance program 2000/2001.

BACKGROUND: PROTEKT US (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin in the United States) was established in 2000 to monitor antimicrobial resistance among respiratory tract pathogens across the United States. METHODS: During 2000 to 2001, 75 southern US centers collected 3,867 Streptococcus pneumoniae, 1,455 Streptococccus pyogenes and 1,042 Haemophilus influenzae. RESULTS: Overall, 46.1% of S. pneumoniae isolates were nonsusceptible to penicillin, 35.8% were resistant to erythromycin, and 0.5% were resistant to fluoroquinolones. Against S. pneumoniae the most active agents were telithromycin (99.7% susceptible), linezolid (99.8%) and the fluoroquinolones (levofloxacin 99.4%, gatifloxacin 99.5%). The prevalence of erythromycin-resistant S. pyogenes isolates was 4.5%. Telithromycin, at concentration of < or = 1 mg/L, inhibited 99.9% of S. pyogenes. The prevalence of beta-lactamase positive H. influenzae was 26.2%. Telithromycin was active (MIC90 4 mg/L) against H. influenzae, irrespective of beta-lactamase production. CONCLUSION: The prevalence of penicillin and macrolide resistance among respiratory tract pathogens from the southern United States is high. Fluoroquinolone resistance is low. Telithromycin is highly active against respiratory tract pathogens with reduced susceptibility to beta-lactams, macrolides, and fluoroquinolones.

Anti-Bacterial Agents↗

Persistent spread of carbapenemase-producing Klebsiella pneumoniae in acute care hospitals in 36 European countries (the CCRE survey): a prospective, multicentre, cross-sectional, epidemiological, microbiological, and genomic surveillance study.

BACKGROUND: Carbapenem-resistant Enterobacterales pose a substantial threat to patients and health-care systems. We conducted a survey of carbapenem-resistant and/or colistin-resistant Enterobacterales (CCRE survey) in 37 European countries to describe their occurrence, geographical distribution, and population dynamics and inform control policies. We report the results of Klebsiella pneumoniae species complex isolates in this study. METHODS: In this cross-sectional, epidemiological, microbiological, and genomic study conducted in all EU, European Economic Area and EU candidate countries as of 2019, hospital microbiology laboratories were selected on the basis of population coverage. Participating laboratories collected, from patient samples, the first ten successive isolates of carbapenem-resistant or carbapenem-susceptible increased exposure (carbapenem-R/I) K pneumoniae species complex or Escherichia coli, and carbapenem-susceptible (carbapenem-S) comparator isolates of the same species, accompanied by patient epidemiological and clinical information. Isolate collection started in 2019, with three possible starting dates-ie, March 1, April 1, or May 1, 2019, and ended after collection of ten carbapenem-R/I and carbapenem-S isolates or a maximum period of 6 months. Isolates were tested for phenotypic susceptibility to 16 antimicrobial agents of relevance to K pneumoniae species complex. Whole-genome sequencing was performed centrally using Illumina technology. Isolates from the CCRE survey were compared with those from the European Survey of Carbapenemase-Producing Enterobacteriaceae (EuSCAPE) study. FINDINGS: 1566 carbapenem-R/I and 1407 carbapenem-S K pneumoniae species complex isolates collected from patients in 302 hospitals in 36 countries (one country did not send isolates) were analysed in this study. The high-risk lineages identified during a previous similar survey in 2013-14 (EuSCAPE) were found to continue to circulate across European hospitals in 2019 (ST11, ST15, ST101, and ST258/512). Moreover, concerning shifts in the pathogen population were observed. First, a higher proportion of carbapenem-R/I isolates was found to carry a carbapenemase gene in the CCRE survey (1398 [89&#xb7;3%] of 1566) than in EuSCAPE (657 [69&#xb7;6%] of 944), mainly related to increased acquisition of carbapenemase genes by high-risk lineages. Of note, among ST307 isolates from all hospitals, the proportion of carbapenem-R/I isolates carrying a carbapenemase gene increased from 14 (60&#xb7;9%) of 23 in EuSCAPE to 164 (91&#xb7;1%) of 180 in the CCRE survey. Second, an expansion of emerging multidrug-resistant lineages (ST147, ST307, and ST39) was also noted: Among 113 hospitals that contributed K pneumoniae species complex isolates to both EuSCAPE and the CCRE survey, the proportion of ST147 increased from 16 (3&#xb7;4%) of 476 in EuSCAPE to 49 (7&#xb7;4%) of 662 carbapenem-R/I isolates in the CCRE survey, that of ST307 increased from 15 (3&#xb7;2%) of 476 to 88 (13&#xb7;3%) of 662, and that of ST39 increased from 3 (0&#xb7;6%) of 476 to 10 (1&#xb7;5%) of 662. Third, there was an increased spread of isolates harbouring acquired virulence loci: isolates with the highest Kleborate virulence score of five increased from 7 (0&#xb7;4%) of 1717 in EuSCAPE to 40 (1&#xb7;3%) of 2973 in the CCRE survey. Notably, the increase was mainly observed in the carbapenem-S-group. INTERPRETATION: The survey findings portray an escalating epidemiological situation and suggest that control measures have not been able to interrupt transmission of high-risk lineages of carbapenemase-producing K pneumoniae in European hospitals. The heterogeneous and evolving situation with regards to circulating lineages and dominant carbapenemase genes requires strengthening and continuous adaptation of diagnostic, treatment, and control measures guided by genomic surveillance. FUNDING: European Centre for Disease Prevention and Control and Centre for Genomic Pathogen Surveillance.

Humans↗

Susceptibility patterns of orally administered antimicrobials among urinary tract infection pathogens from hospitalized patients in North America: comparison report to Europe and Latin America. Results from the SENTRY Antimicrobial Surveillance Program (2000).

Urinary tract infections (UTIs) remain a worldwide nosocomial infection problem. Geographic variations in pathogen occurrence and susceptibility profiles require monitoring to provide information to guide new (garenoxacin [BMS284756]) therapeutic options. Two thousand seven hundred-eighty UTI isolates from Europe (n = 783), Latin America (531), and North America (1,466) were tested and compared against 44 agents by reference methods in the SENTRY Antimicrobial Surveillance Program. The top seven pathogens accounted for 90% of all isolates and the rank order for all regions was: Escherichia coli (1,316; 47%), Enterococcus spp. (351; 13%), Klebsiella spp. (306; 11%), Pseudomonas aeruginosa (210; 8%), Proteus mirabilis (145; 5%), Enterobacter spp. (97; 4%), and Citrobacter spp. (78; 3%). The pathogen rank order was similar among regions except for the rarer occurrence of Enterococcus spp. (Rank #6, 4%) in Latin America. E. coli ampicillin resistance was highest in Europe and Latin America (51-55%). Ampicillin (37%), ciprofloxacin or garenoxacin (4%), and trimethoprim/sulfamethoxazole (23%) resistance remained lowest in North America. Nitrofurantoin susceptibility in E. coli was still at acceptable levels and ranged from 91 to 96% across regions. The regional ciprofloxacin-resistant rank order for P. aeruginosa by region was: Latin America (55%) > Europe (41%) > North America (29%). Vancomycin-resistant enterococci (VRE) were only detected in North America (7%). Garenoxacin possessed a 34 to 44% wider spectrum compared to ciprofloxacin against enterococci UTI isolates. Extended spectrum beta-lactamase rates for E. coli and Klebsiella spp. were 4 and 19%, respectively. These results emphasized the need to assess the often striking differences in pathogen occurrence and resistance rates among the commonly encountered UTI pathogens.

Administration, Oral↗

[Methods for population-based herd sanitation: an overview].

There is a considerable number of methods available for the development, maintenance and surveillance of specific-pathogen-free herds. The selection of a method for a specific remediation project is primarily dependent on the goal, the epidemiology of the agent to be eradicated, the feasibility and the available resources. At the beginning of the remediation programme, methods are required for the classification of the herd status. Clinical and analytical diagnostic tests may be used for individual herds or in an entire area. The interpretation of test results applied within a population deserves special attention. A series of techniques are available - alone or in combination - to remediate a herd that was classified as being infected: systematic treatment, vaccination, elimination of infected individual animals ("test and remove"), partial depopulation or total population (stamping out). These strategies are typically accompanied by cleaning and disinfection. After the remediation, the status of the herd needs to be certified and maintained. For the documentation of the status, monitoring and surveillance strategies such as clinical follow-up visits, notification systems and random sampling can be applied. When planning random surveys, statistical and epidemiological considerations are relevant. For the sustainable maintenance of the pathogen-free status, biosecurity measures at the individual farm level, but also broader approaches such as import restrictions, early warning systems and surveillance programmes are needed. General awareness regarding unusual clinical signs needs to be promoted among farmers and veterinarians. The longer a disease or an agent is absent from a herd or region, the lower becomes the risk awareness. In such a situation, mistakes can occur leading to an increased risk of re-infection.

Animal Diseases↗

Host-microbe interactions: shaping the evolution of the plant immune response.

The evolution of the plant immune response has culminated in a highly effective defense system that is able to resist potential attack by microbial pathogens. The primary immune response is referred to as PAMP-triggered immunity (PTI) and has evolved to recognize common features of microbial pathogens. In the coevolution of host-microbe interactions, pathogens acquired the ability to deliver effector proteins to the plant cell to suppress PTI, allowing pathogen growth and disease. In response to the delivery of pathogen effector proteins, plants acquired surveillance proteins (R proteins) to either directly or indirectly monitor the presence of the pathogen effector proteins. In this review, taking an evolutionary perspective, we highlight important discoveries over the last decade about the plant immune response.

Bacteria↗

The National Nosocomial Infections Surveillance System: plans for the 1990s and beyond.

The National Nosocomial Infections Surveillance (NNIS) System is an ongoing collaborative surveillance system among the Centers for Disease Control (CDC) and United States hospitals to obtain national data on nosocomial infections. This system provides comparative data for hospitals and can be used to identify changes in infection sites, risk factors, and pathogens, and develop efficient surveillance methods. Data are collected prospectively using four surveillance components: hospital-wide, intensive care unit, high-risk nursery, and surgical patient. The limitations of NNIS data include the variability in case-finding methods, infrequency or unavailability of culturing, and lack of consistent methods for post-discharge surveillance. Future plans include more routine feedback of data, studies on the validity of NNIS data, new components, a NNIS consultant group, and more rapid data exchange with NNIS hospitals. Increasing the number of NNIS hospitals and cooperating with other agencies to exchange data may allow NNIS data to be used better for generating benchmark nosocomial infection rates. The NNIS system will continue to evolve as it seeks to find more effective and efficient ways to measure the nosocomial infection experience and assess the influence of patient risk, changes in the delivery of hospital care, and changes in infection control practices on these measures.

Centers for Disease Control and Prevention, U.S.↗