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Extended-spectrum beta-lactamases (ESbLs): characterization, epidemiology and detection.

Beta-lactamases of Enterobacteriaceae are the most important mechanism of resistance against beta-lactam drugs. Two types of beta-lactamases can confer resistance against 3rd generation cephalosporins. Chromosomally mediated beta-lactamases are inducible and are not inhibited by clavulanic acid. Resistance due to these enzymes is non-transferable. The 2nd type of enzyme is plasmid-mediated beta-lactamases, which are inhibited by clavulanic acid. These enzymes are more important clinically as these can be transferred between various species of Enterobacteriaceae. These enzymes are called extended-spectrum beta-lactamases (ESBLs). ESBL-producing Enterobacteriaceae have been responsible for numerous outbreaks of infection throughout the world and pose challenging infection control issues. Antibacterial choice is often complicated by multi-resistance. ESBLs can confer resistance against all beta-lactam drugs except carbapenems and cephamycins. Nursing home patients may be an important reservoir of ESBL-containing multiple antibiotic-resistant organisms. Use of broad-spectrum oral antibiotics and probably poor infection control practices may facilitate spread of this plasmid-mediated resistance. In addition to known populations at risk, ambulatory patients with chronic conditions represent another patient population that may harbor ESBL-producing organisms. Various methods can be used for detection of ESBLs in the laboratory. These tests include double disc diffusion test, Vitek ESBL test, E Tests, MIC Determination, genetic method, and isoelectric focusing (IEF).

Anti-Bacterial Agents↗

A new family of potent AB(5) cytotoxins produced by Shiga toxigenic Escherichia coli.

The Shiga toxigenic Escherichia coli (STEC) O113:H21 strain 98NK2, which was responsible for an outbreak of hemolytic uremic syndrome, secretes a highly potent and lethal subtilase cytotoxin that is unrelated to any bacterial toxin described to date. It is the prototype of a new family of AB(5) toxins, comprising a single 35-kilodalton (kD) A subunit and a pentamer of 13-kD B subunits. The A subunit is a subtilase-like serine protease distantly related to the BA_2875 gene product of Bacillus anthracis. The B subunit is related to a putative exported protein from Yersinia pestis, and binds to a mimic of the ganglioside GM2. Subtilase cytotoxin is encoded by two closely linked, cotranscribed genes (subA and subB), which, in strain 98NK2, are located on a large, conjugative virulence plasmid. Homologues of the genes are present in 32 out of 68 other STEC strains tested. Intraperitoneal injection of purified subtilase cytotoxin was fatal for mice and resulted in extensive microvascular thrombosis, as well as necrosis in the brain, kidneys, and liver. Oral challenge of mice with E. coli K-12-expressing cloned subA and subB resulted in dramatic weight loss. These findings suggest that the toxin may contribute to the pathogenesis of human disease.

Amino Acid Sequence↗

Progress toward measles elimination in Romania after a mass vaccination campaign and implementation of enhanced measles surveillance.

In response to an outbreak of >33,000 measles cases in 1996-1998 and to prevent an outbreak predicted for 2002, Romania conducted a nationwide measles-rubella vaccination campaign in October 1998. Some 2.1 million children aged 7-18 years were vaccinated. Data from national surveillance and seroprevalence studies conducted in three districts were used to assess the campaign and status of measles control. Surveillance data showed a dramatic drop in measles despite enhanced surveillance starting in October 1999. From October 1999 to December 2001, 400 suspected measles cases were reported, down from about 5000 cases annually in non-outbreak years. Only 29 (8%) of 386 cases with specimens were laboratory confirmed; 14 were clinically confirmed. Seroprevalence estimates showed high measles antibody levels before (92.9%) and after (94.4%) the campaign. The low number of laboratory-confirmed cases and high population immunity suggest that interruption of indigenous measles virus transmission is a real possibility for Romania.

Adolescent↗

Increasing prevalence of methicillin-resistant Staphylococcus aureus infection in California jails.

Staphylococcus aureus clinical isolates obtained from patients who were inmates of the San Francisco County jail system showed an increase in the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) from 29%, in 1997, to 74%, in 2002; 91% of the MRSA isolates carried staphylococcal chromosomal cassette mec (SCCmec) type IV. Pulsed field gel electrophoresis and multilocus sequence typing demonstrated 2 major clonal groups. One of these clonal groups is genetically indistinguishable from the strain responsible for an outbreak of MRSA in the Los Angeles County jail system in 2002.

Anti-Bacterial Agents↗

Serological analysis of serum samples from humans exposed to avian H7 influenza viruses in Italy between 1999 and 2003.

We evaluated the potential for avian-to-human transmission of low pathogenic avian influenza (LPAI) and highly pathogenic avian influenza (HPAI) H7N1 and LPAI H7N3 viruses that were responsible for several outbreaks of influenza in poultry in Italy between 1999 and 2003. A serological survey of poultry workers was conducted by use of a combination of methods. Evidence of anti-H7 antibodies was observed in 3.8% of serum samples collected from poultry workers during the period in 2003 when LPAI H7N3 virus was circulating. These findings highlight the need for surveillance in people occupationally exposed to avian influenza viruses, so that they can be monitored for the risk of avian-to-human transmission during outbreaks of avian influenza caused by both LPAI and HPAI viruses.

Agricultural Workers' Diseases↗

The emerging nosocomial pathogens Cryptosporidium, Escherichia coli O157:H7, Helicobacter pylori, and hepatitis C: epidemiology, environmental survival, efficacy of disinfection, and control measures.

New and emerging infectious diseases pose a threat to public health and may be responsible for nosocomial outbreaks. Cryptosporidium parvum and Escherichia coli are gastrointestinal pathogens that have caused nosocomial infections via person-to-person transmission, environmental contamination, or contaminated water or food. Helicobacter pylori has been transmitted via inadequately disinfected endoscopes. Finally, hepatitis C may be acquired by healthcare personnel by percutaneous or mucous membrane exposure to blood or between patients by use of contaminated blood products or via environmental contamination. Rigorous adherence to Standard Precautions, Contact Precautions for patients with infectious diarrhea, disinfection of environmental surfaces, and appropriate disinfection of endoscopes are adequate to prevent nosocomial acquisition of these pathogens.

Animals↗

Nosocomial transmission of imipenem-resistant Pseudomonas aeruginosa following bronchoscopy associated with improper connection to the Steris System 1 processor.

OBJECTIVE: To assess nosocomial transmission of imipenem-resistant Pseudomonas aeruginosa (IRPA) following bronchoscopy during August through October 1998. DESIGN: Traditional and molecular epidemiological investigation of a case series. SETTING: University-affiliated community hospital. PATIENTS: 18 patients with IRPA bronchial-wash isolates. INTERVENTIONS: We reviewed clinical data, performed environmental cultures and molecular analysis of all IRPA isolates, and observed disinfection of bronchoscopes. RESULTS: Of 18 patients who had IRPA isolated from bronchoscopic or postbronchoscopic specimens, 13 underwent bronchoscopy for possible malignancy or undiagnosed pulmonary infiltrates. Following bronchoscopy, 3 patients continued to have IRPA isolated from sputum and demonstrated clinical evidence of infection requiring specific antimicrobial therapy. The remaining 15 patients had no further IRPA isolated and remained clinically well 3 months following bronchoscopy. Pulsed-field gel electrophoresis revealed that all strains except one were >95% related. STERIS SYSTEM 1 had been implemented in July 1998 as an automatic endoscope reprocessor (AER) for all endoscopes and bronchoscopes. Inspection of bronchoscope sterilization cycles revealed incorrect connectors joining the bronchoscope suction channel to the STERIS SYSTEM 1 processor, obstructing peracetic acid flow through the bronchoscope lumen. No malfunction warning was received, and spore strips remained negative. CONCLUSIONS: The similarity of diverse connectors and limited training by the manufacturer regarding AER for bronchoscopes were the two factors responsible for the outbreak. Appropriate connections were implemented, and there was no further bronchoscope contamination. We suggest active surveillance of all bronchoscopy specimen cultures, standardization of connectors of various scopes and automated processors, and systematic education of staff by manufacturers with periodic on-site observation.

Bronchoscopes↗

Evaluation of infection control measures in preventing the nosocomial transmission of multidrug-resistant Mycobacterium tuberculosis in a New York City hospital.

OBJECTIVE: To evaluate the efficacy of Centers for Disease Control and Prevention (CDC)-recommended infection control measures implemented in response to an outbreak of multidrug-resistant (MDR) tuberculosis (TB). DESIGN: Retrospective cohort studies of acquired immunodeficiency syndrome (AIDS) patients and healthcare workers. The study period (January 1989 through September 1992) was divided into period I, before changes in infection control; period II, after aggressive use of administrative controls (eg, rapid placement of TB patients or suspected TB patients in single-patient rooms); and period III, while engineering changes were made (eg, improving ventilation in TB isolation rooms). SETTING: A New York City hospital that was the site of one of the first reported outbreaks of MDR-TB among AIDS patients in the United States. PARTICIPANTS: All AIDS patients admitted during periods I and II. Healthcare workers on nine inpatient units with TB patients and six without TB patients. RESULTS: The epidemic (38 patients) waned during period II and only one MDR-TB patient presented during period III. The MDR-TB attack rate among AIDS patients hospitalized on the same ward on the same days as an infectious MDR-TB patient was 8.8% (19 of 216) during period I, decreasing to 2.6% (5 of 193; P = 0.01) during period II. In a small group of healthcare workers with tuberculin skin test data, conversions during periods II through III were higher on wards with than without TB patients (5 of 29 versus 0 of 15; P = 0.15), although the difference was not statistically significant. CONCLUSIONS: Transmission of MDR-TB among AIDS patients decreased markedly after enforcement of readily implementable administrative measures, ending the outbreak. However, tuberculin skin-test conversions among healthcare workers may not have been prevented by these measures. CDC guidelines for prevention of nosocomial transmission of TB should be implemented fully at all US hospitals.

AIDS-Related Opportunistic Infections↗

Control of methicillin-resistant Staphylococcus aureus in a neonatal intensive-care unit: use of intensive microbiologic surveillance and mupirocin.

OBJECTIVE: To describe the epidemiology and the interventions used to control two methicillin-resistant Staphylococcus aureus (MRSA) epidemics involving 46 infants with two fatalities in a neonatal intensive care unit (NICU). SETTING: A 50-bed, level III NICU in a university hospital. INTERVENTIONS: After traditional interventions failed to stop the first epidemic, an intensive microbiologic surveillance (IMS) program was developed. Cultures were obtained on all infants each week, and those colonized with MRSA were isolated. When an infant was found to be colonized with MRSA, cultures immediately were obtained on all surrounding infants. This was continued until no MRSA-colonized infants were found in the area. During the first epidemic, mupirocin was used in an attempt to eradicate the organism from the unit. RESULTS: All infants, colonized and noncolonized, and parents of and personnel working with colonized infants were treated simultaneously with 5 days of mupirocin. This failed to eradicate MRSA in colonized infants. The spread of MRSA ceased in the unit, but a second epidemic occurred 4 months later. This time, IMS alone was successful in quickly containing the epidemic, and MRSA disappeared from the unit after all colonized infants were discharged. Plasmid analysis demonstrated that the same strain was responsible for both outbreaks. CONCLUSIONS: IMS and isolation are effective in containing the spread of MRSA in an NICU. The use of mupirocin failed to eradicate the organism.

Anti-Bacterial Agents↗

Persistence of a multiresistant clone of Staphylococcus epidermidis in a neonatal intensive-care unit for a four-year period.

A cluster of cases of Staphylococcus epidermidis bacteremia in a neonatal intensive-care unit (NICU) during 1991 raised the question of whether these infections were caused by a single strain. Sixty-seven isolates of S. epidermidis from blood cultures of 56 neonates treated in the NICU between 1986 and 1992 and 54 control strains from other patients with bacteremia were characterized by three typing methods: antibiogram, plasmid profile, and ribotype. Plasmid profiles and ribotype patterns indicated that 11 (16%) of the 67 episodes of S. epidermidis bacteremia in the NICU were caused by a single strain. Although this epidemic strain did not account entirely for the increase in the incidence of bacteremia in the NICU, it did persist for 4 years during the study period. Other clones responsible for smaller outbreaks were also found. These results suggest that S. epidermidis cross-infections are very common in the NICU setting.

Bacteremia↗

Multidrug-resistant Salmonella typhi: a worldwide epidemic.

Since 1989, strains of Salmonella typhi resistant to chloramphenicol, ampicillin, and trimethoprim (i.e., multidrug-resistant [MDR] strains) have been responsible for numerous outbreaks in countries in the Indian subcontinent, Southeast Asia, and Africa. MDR strains have also been isolated with increasing frequency from immigrant workers in countries in the Arabian Gulf, as well as in developed countries from returning travelers. In all MDR strains so far examined, multiple resistance has been encoded by plasmids of the H1 incompatibility group. As a result of the widespread dissemination of such strains, chloramphenicol can no longer be regarded as the first-line drug for typhoid fever. Because strains are also resistant to ampicillin and trimethoprim, the efficacy of these antibiotics has also been impaired, and ciprofloxacin is now the drug of choice for typhoid fever. Chromosomally encoded resistance to ciprofloxacin has now been observed in a small number of strains isolated in the United Kingdom from patients returning from the Indian subcontinent, and in at least one case the patient did not respond to treatment with this antibiotic. It is regrettable that resistance to ciprofloxacin has now emerged in MDR S. typhi, and it is of paramount importance to limit the unnecessary use of this vital drug so that its efficacy should not be further jeopardized.

Developed Countries↗

Virulence factors of enterotoxigenic Escherichia coli.

Further evidence for the role of enterotoxigenic Escherichia coli as an etiologic agent of diarrhea is presented. A retrospective study of 71 cases of diarrhea in Mexican children demonstrated that greater than 40% of them harbored E. coli that produced heat-labile and/or heat-stable enterotoxin. The antigenic surface-associated colonization factor of E. coli strain H-10407 has been further characterized: this pilus-like antigen is produced under conditions of growth that repress the production of common pili of E. coli. The E. coli H-10407-type colonization factor pilus has been identified as one of the antigens possessed by a strain of E. coli that produced only heat-stable enterotoxin and that was responsible for an outbreak of pediatric diarrhea.

Antigens, Bacterial↗

Influenza RNA not detected in archival brain tissues from acute encephalitis lethargica cases or in postencephalitic Parkinson cases.

Encephalitis lethargica (EL) was a mysterious epidemic. temporally associated with the 1918 Spanish influenza pandemic. Numerous symptoms characterized this disease, including headache, diplopia, fever, fatal coma, delirium, oculogyric crisis, lethargy, catatonia, and psychiatric symptoms. Many patients who initially recovered subsequently developed profound, chronic parkinsonism. The etiologic association of influenza with EL is controversial. Five acute EL autopsies and more than 70 postencephalitic parkinsonian autopsies were available in the Armed Forces Institute of Pathology (AFIP) tissue repository. Two of these 5 acute EL cases had histopathologic changes consistent with that diagnosis. The remaining 3 cases were classified as possible acute EL cases as the autopsy material was insufficient for detailed histopathologic examination. RNA lysates were prepared from 29 CNS autopsy tissue blocks from the 5 acute cases and 9 lysates from blocks containing substantia nigra from 2 postencephalitic cases. RNA recovery was assessed by amplification of beta-2-microglobulin mRNA and 65% of the tissue blocks contained amplifiable RNA. Reverse transcription-polymerase chain reaction (RT-PCR) for influenza matrix and nucleoprotein genes was negative in all cases. Thus, it is unlikely that the 1918 influenza virus was neurotropic and directly responsible for the outbreak of EL.

Adult↗

The control of mosquito-borne diseases in New York City.

Mosquito control began in New York City in 1901. Large-scale efforts to drain marshlands occurred through the 1930s, and aerial application of pesticide occurred as early as 1956. Components of early mosquito-borne disease control were reimplemented in 1999-2000 in response to an outbreak of West Nile virus, and included promoting public and health professional awareness regarding disease causation and prevention, providing free government laboratory testing, case reporting, mapping of mosquito breeding sites and their elimination or application of larvicide to them, and adult mosquito control. Because a potential for various mosquito-borne diseases in New York City persists, continued efforts are warranted to limit mosquito breeding, to monitor adult mosquito populations for the presence of human pathogens, and to establish protocols and capacity for adult mosquito control.

Animals↗

Seasonal and racial incidence of infantile gastroenteritis in South Africa.

The etiology of summer diarrhea, which formerly caused extensive mortality in children living in industrialized countries, was never discovered. This condition no longer occurs in developed countries, having been replaced by winter diarrhea, which is associated with a low mortality. Summer epidemics of diarrhea still take place in black South African infants, whereas, in white South African children, the pattern of diarrhea is similar to that seen in children in industrialized countries today. In 1977-1980, the author studied the records of patients less than two years of age admitted for treatment of dehydrating diarrhea to two teaching hospitals in Johannesburg, the Johannesburg General and Baragwanath Hospitals, which serve the needs of white and black patients, respectively. The incidence of severe diarrhea (i.e., diarrhea necessitating hospitalization) showed highly significant seasonality (p less than 0.001) and distinctive patterns by race. Dehydrating diarrhea in black children was strongly associated with warm weather, while diarrhea in white children occurred more regularly throughout the year, with a peak incidence in late fall. Laboratory studies have shown that bacteria, in particular "classical" enteropathogenic Escherichia coli, are the leading cause of diarrhea in black South African children, and that diarrhea in white children is largely attributable to rotaviruses. The association of enteropathogenic E. coli with diarrhea in black children suggests that these bacteria were responsible for earlier outbreaks of summer diarrhea. The finding that the etiology of diarrhea varies according to socioeconomic class has important implications for diarrhea control programs.

Black People↗

Geographic distribution and evolution of yellow fever viruses based on direct sequencing of genomic cDNA fragments.

We have compared the nucleotide sequence of an envelope protein gene fragment encoding amino acids 291 to 406 of 22 yellow fever (YF) virus strains of diverse geographic and host origins isolated over a 63 year time span. The nucleotide fragment of viral RNA was examined by direct sequencing of a PCR product derived from complementary DNA. Alignment with the prototype Asibi strain sequence showed divergence of 0 to 21.5% corresponding to a maximum of 5.2% divergence in the amino acid sequence. Taking 10% nucleotide divergence as a cut-off point, the 22 YF virus strains fell into three topotypes which corresponded to different geographical areas, namely West Africa, Central-East Africa, and South America. Two subgroups were defined in West Africa, a genotypic group circulating in the sylvatic zone of the western part of Africa, from western Ivory Coast-Mali to Senegal, and a group responsible for large outbreaks from eastern Ivory Coast-Burkina Faso to Cameroon. Strains from Central-East Africa showed a low ratio of transition:transversion of about 1 instead of 8 to 10 for other strains, when their nucleotide sequences were compared with those of other African strains. This may reflect a more distant relationship between the former strains and the others. No change was observed in the highly conserved amino acid domain encompassing the TGD sequence, an important determinant of flavivirus tropism and pathogenesis. Our results support earlier observations on the genetic relationships between YF isolates established by T1 oligonucleotide fingerprinting and offer a useful tool for the understanding of YF virus distribution and evolution.

Amino Acid Sequence↗

Human infection in Tayside, Scotland due to Salmonella serotype Livingstone.

Livingstone was the third most common salmonella serotype isolated from cases of human salmonellosis in the Tayside region of Scotland in 1989-1991; latterly, it spread to Grampian region. The significant upsurge of Livingstone in these two Scottish regions was not matched by similar increases in its frequency of isolation from human cases of salmonellosis in other regions of Scotland or elsewhere in the UK. Although Salmonella Livingstone is usually associated in the UK with incidents of infection among poultry flocks, our detailed investigations found no clear evidence that poultry, eggs or poultry-related products were responsible for this outbreak. Most cases occurred in the summer months from July to September and many of the patients required hospital treatment. Other than one outbreak among geriatric patients in a long-stay hospital in north Tayside, most of the cases were sporadic. The extent of the outbreak, covering 3 years, was recognised mainly because Livingstone was previously an uncommon serotype in Tayside. There were few Livingstone isolations from non-human sources in Scotland in these same years. Possible sources of infection and predisposing factors among patients are discussed. Livingstone was not isolated in Scotland in 1992.

Adolescent↗

Long-term investigation of the clonal dissemination of Klebsiella pneumoniae isolates producing extended-spectrum beta-lactamases in a university hospital.

Seventy isolates of Klebsiella pneumoniae with extended-spectrum beta-lactamases (ESBLs) were compared. These were isolated from 51 patients on 10 separate wards in one hospital over an 18-month period between 1992 and 1994. Antibiograms were determined and the isolates were typed by pulsed-field gel electrophoresis of their DNA digestion with XbaI. The isolates were compared to three genotypically different epidemic strains responsible for previous outbreaks at the hospital between 1988 and 1991. Isolates from 84% of the present patients had closely related XbaI patterns, and most (74%) produced an ESBL with an iso-electric point (pI) of 7.0. A similar pattern was found for one of the previous epidemic strains, but it produced an ESBL with a pI of 7.8; isolates with this latter enzyme variant were found only in six of the present patients. The two other previous epidemic strains had ESBLs with a pI of 6.3 and organisms related to them were found in one and two of the present patients, respectively.

Cephalosporins↗