Campylobacter antimicrobial resistance in Peru: a ten-year observational study

ABSTRACT: BACKGROUND: : Campylobacter jejuni and Campylobacter coli are food-borne pathogens of great importance and feature prominently in the etiology of developing world enteritis and travellers' diarrhoea. Increasing antimicrobial resistant Campylobacter prevalence has been described globally, yet data from Peru is limited. Our objective was to describe the prevalence trends of fluoroquinolone and macrolide-resistant C. jejuni and C. coli stool isolates from three regions in Peru over a ten-year period. METHOD: S: Surveillance for enteric pathogens was conducted in Lima, Iquitos and Cusco between 2001 and 2010. Campylobacter stool isolates were tested for susceptibilities to ciprofloxacin, azithromycin and erythromycin. Susceptibilities were reviewed for 4652 isolates from Lima (n = 3419), Iquitos (n = 625) and Cusco (n=608). RESULTS: : Comparing the study periods of 2001-2005 and 2006-2010, prevalence of ciprofloxacin-resistant C.jejuni isolates rose in the study areas of Lima (73.1% to 89.8%, p < 0.001) and Iquitos (24.1% to 48.9%, p < 0.001). Ciprofloxacin-resistant C.coli rates also increased in Lima (48.1% to 87.4%, p < 0.001) and Cusco (10.0% to 65.9%, p = 0.005). Small but significant increases in azithromycin-resistant and erythromycin-resistant C. jejuni prevalence were noted in Iquitos (2.2% to 14.9%, p < 0.001; 3.2% to 14.9%, p = 0.002), and erythromycin-resistant C.coli rates increased in Lima (0.0% to 5.3%, p = 0.038). The prevalence of C.jejuni isolates resistant to both ciprofloxacin and azithromycin increased in Iquitos (0.3% to 14.9%, p < 0.001) and Lima (0.3% to 1.6%, p = 0.011), and prevalence of C.jejuni isolates resistant to both ciprofloxacin and erythromycin rose in Iquitos (0.0% to 14.9%, p < 0.001). Ciprofloxacin and erythromycin resistant C.coli prevalence increased in Lima (0.0% to 5.3%, p = 0.034). CONCLUSIONS: : These results have implications for the empirical management of enterocolitis in Peru. Ongoing surveillance is essential to guide appropriate antimicrobial use in this setting. Local epidemiological studies to explore the relationship between increasing antimicrobial resistance and agricultural or human antibiotic use may be valuable.     

Adverse consequences of immediate thrombolysis-related complications: a multi-centre registry-based cohort study of acute stroke

Journal of Thrombosis and Thrombolysis - Complications following thrombolysis for stroke are well documented, and mostly concentrated on haemorrhage. However, the consequences of patients who...     

Prognosis of patients with a diagnosis of fatty liver--a registry-based cohort study

BACKGROUND/AIMS: There are very limited data available regarding the prognosis of patients with fatty liver. We examined the overall and cause-specific mortality of fatty liver patients in a large Danish cohort. METHODOLOGY: In the Danish National Registry of Patients, we identified 7,372 patients discharged with a diagnosis of fatty liver from a Danish hospital between 1977 and 1993. Causes of death were identified in the Danish Death Registry. We estimated the standardized mortality ratio by comparing with the general population. RESULTS: Most patients (76%) had alcoholic fatty liver. During follow-up, 2,914 (40%) died. The commonest cause of death was hepatobiliary disease (25% of deaths). Mortality was increased 5.4-fold (95% CI 5.2-5.6) in patients with alcoholic fatty liver, and 2.6-fold (95% CI 2.4-2.9) in patients with non-alcoholic or unspecified fatty liver. Overall, in the first year of follow-up, mortality was increased more than 7-fold, almost 5-fold in the second to fifth years, and more than 3-fold after that. Mortality was similar among genders and among diabetics and non-diabetics, and remained increased after censoring patients upon diagnosis of liver cirrhosis. CONCLUSIONS: The mortality of patients with a hospital discharge diagnosis of fatty liver was higher than that of the general population.     

Adverse events associated with methicillin-resistant Staphylococcus aureus in a nursing home

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) generates concern in nursing homes. Restrictive isolation precautions may be applied for indefinite periods. Adverse events driving these concerns include transmission and infection. METHODS: The 721-bed Wisconsin Veterans Home in King performs approximately 645 cultures annually. The site, severity, and number of MRSA infections were determined for 69 months. Pulsed-field gel electrophoresis was performed on all initial isolates, followed by a statistical cluster analysis looking for evidence of transmission. RESULTS: Sixty-seven MRSA infections were identified (1.6 per 100 residents per year); many were polymicrobial, and it was difficult to determine the proportionate role of MRSA in morbidity or mortality. There was an episode of rapidly fatal MRSA septicemia in which empiric antibiotic therapy was ineffective. Twenty-one genetic strains were encountered. Statistical analysis identified 13 clusters of genetically identical strains clustered in time and space (P<.05). CONCLUSIONS: Infections with MRSA were identified at relatively low rates; however, the etiology of many serious nursing home infections is not determined, especially pneumonia. Statistical analysis revealed clustering and evidence of transmission. Nursing home practitioners should consider MRSA when applying empiric treatment to serious infections. We recommend a program including (1) judicious use of antibiotics, including topical agents, to reduce selection of resistant organisms; (2) obtaining and tracking cultures of infectious secretions to diagnose MRSA infections and focus antibiotic therapy; (3) universal standard secretion precautions because any resident could be a carrier; and (4) a detailed assessment and care plan for the carrier that maximizes containment of secretions and independence in activities. However, basic hygiene cannot be maintained in communal areas by some residents without restriction of activities of daily living.     

Adverse events with disease modifying antirheumatic drugs (DMARD): a cohort study of leflunomide compared with other DMARD

OBJECTIVE: To determine and compare the incidence of serious adverse events (AE) during treatment of rheumatoid arthritis (RA) with disease modifying antirheumatic drugs (DMARD), focusing on leflunomide (LEF). METHODS: A retrospective cohort study of a large US insurance claims database was performed. Study groups were patients with RA classified by DMARD exposure as either no-DMARD therapy, single-agent DMARD (monotherapy), or combination-DMARD therapy. Specific DMARD examined were leflunomide (LEF) and methotrexate (MTX), compared to other DMARD (penicillamine, hydroxychloroquine, sulfasalazine, gold, etanercept, infliximab) and no DMARD (nonsteroidal antiinflammatory drugs, COX-2 inhibitors). All AE reported were considered endpoints; primary endpoints included hepatic, dermatologic, hematologic, infectious, respiratory, hypertension, and pancreatitis AE. RESULTS: The 40,594 RA patients of the study period (September 1998 to December 2000) accumulated 83,143 person-years (PY) of followup. Followup for each of the groups was: DMARD-monotherapy, 46,054 PY (55% of total); combination-DMARD, 25,830 PY (14%); and no-DMARD, 11,259 PY (14%). The incidence rate of all AE combined was significantly lower for LEF monotherapy (94 events/1000 PY) than MTX (145 events/1000 PY), other DMARD (143 events/1000 PY), or no DMARD (383 events/1000 PY) (p < 0.001 for all comparisons). The "all-AE" rates during combination therapy with LEF + MTX (43/1000 PY) and LEF + other DMARD (59/1000 PY) were lower than the "all-AE" rate for DMARD + MTX (70/1000 PY; p = 0.002). LEF monotherapy had the lowest rate of hepatic events in the DMARD monotherapy groups. CONCLUSION: The rates of AE in the LEF group, alone and combined with MTX, were generally lower than or comparable to the AE rates seen with MTX and other agents.     

Adverse drug events in emergency department patients

STUDY OBJECTIVE: Adverse drug events (ADEs) have been studied in hospitalized patients. Less is known about this common type of injury in emergency department patients. This study seeks to measure the risks, incidence, severity, and costs of ADEs in an ED population. METHODS: ED charts of visits to a university-affiliated tertiary-care ED occurring between March 1 and May 31, 1997, were retrospectively reviewed. The main outcome measures were ADE incidence, severity, and total cost. Visits identified by investigators as containing a suspected ADE were further assessed by using the Naranjo Adverse Drug Reaction (ADR) probability scale. Events judged as probable ADEs (Naranjo ADR probability scale score of >4) were compared with ED control visits best matched by age for disposition, survival, severity, payer, sex, race, age, number of drugs, and total cost. RESULTS: Of 13,602 visits, 13,004 records were available. Three hundred twenty-one had suspected and 217 had probable ADEs (1.7% of evaluable encounters); these were compared with visits by 217 age-matched control patients. Insulin and warfarin were the most commonly responsible drugs. Patients with ADEs were older (mean age 45.1 versus 36.8 years; mean difference 8.3; 95% confidence interval [CI] 3.7 to 12.9), were more often women (odds ratio [OR] 1.48; 95% CI 1.01 to 2.16), took more drugs (mean number of drugs 4.1 versus 1.9; mean difference 2.2; 95% CI 1.7 to 2.8), and were hospitalized more frequently (OR 2.29; 95% CI 1.33 to 3.94) than control patients. CONCLUSION: ADEs encompassed an important segment of ED encounters and annual health care costs. ED screening may provide useful information about the epidemiology of outpatient ADEs.     

Adverse drug events in hospitalized cardiac patients

Little information is available concerning adverse drug events (ADEs) in cardiac patients. Therefore, the investigators report the results of cardiac patients in an ADE surveillance program, with the intent of reducing the frequency of future events. All reported adverse drug reactions and medication errors in cardiac patients over a 5-year period at Brigham and Women's Hospital were reviewed. There were 547 ADEs in cardiac patients, a rate of 1.9 events for every 100 patient admissions. Preventable ADEs most often occurred during medication administration (34.2%), with wrong rate or frequency of medication administration the most widespread event. Cardiovascular agents (29.8%), anticoagulants (28.5%), and antimicrobial agents (10.8%) were the most common drug classes associated with ADEs. Injury or prolonged hospitalization occurred in 5.3% of patients. ADEs occurred most frequently on the admission day, on weekdays, and in the early morning hours. Peak frequencies of ADEs coincided with nursing shift changes. In conclusion, ADEs occur often in hospitalized cardiac patients and affect 2 of every 100 patient admissions. Given the high percentage of ADEs associated with drug administration, more resources should be directed at this step of medication use. Focusing interventions around nursing shift changes may further enhance preventive strategies.     

Association of antimicrobial resistance in Campylobacter isolated from food-producing animals with antimicrobial use on farms

On 1,374 food-producing animal farms in 2001-2004, we investigated the influence of antimicrobial usage within 6 months before a survey conducted on antimicrobial resistance in Campylobacter. Tetracyclines and fluoroquinolones were used for therapeutic purposes on 107 and 21 farms, respectively. Oxytetracycline-resistant C. jejuni and C. coli were found in 57.1% (8/14) and 92.5% (37/40) of the farms, respectively, when the animals were treated with tetracyclines. However, they were found in 43.2% (112/259) and 74.3% (122/164) of the farms, respectively, when the animals were not treated with tetracyclines. Enrofloxacin-resistant C. jejuni and C. coli were found in 66.7% (2/3) and 16.7% (1/6) of the farms, respectively, when the animals were treated with fluoroquinolones. However, they were found in 15.5% (42/270) and 28.8% (57/198) of the farms, respectively, when the animals were not treated with fluoroquinolones. The percentage of oxytetracycline resistance in C. coli was significantly elevated when the animals were treated with tetracyclines (P < 0.05). The farms on which antimicrobials included by their resistance pattern were used accounted for 9.1% (4/44) and 24.1% (14/58) of the farms where enrofloxacin-resistant C. jejuni and C. coli were isolated, respectively. It is likely that several factors account for the presence of fluoroquinolone-resistant Campylobacter.     

Multiple drug class-wide resistance associated with poorer survival after treatment failure in a cohort of HIV-infected patients

OBJECTIVE: To evaluate the effect of drug class-wide resistance (CWR) on survival in HIV-infected individuals who underwent genotypic resistance test after antiretroviral failure. DESIGN: Observational, longitudinal cohort study. METHODS: HIV-infected individuals experiencing treatment failure were enrolled at first genotypic resistance test. End-points were death for any cause, AIDS-related death and AIDS-defining event/death. CWR was defined according to the International AIDS Society consensus. Survival analysis was performed with Cox's model. RESULTS: Among 623 patients enrolled and followed for a median of 19 months (interquartile range, 12-29), Kaplan-Meier analyses for end-points at 48 months in patients with no CWR, one CWR, two CWR or three CWR were 8.9, 11.7, 13.4 and 27.1%, respectively, for death; 6.1, 9.9, 13.4 and 21.5%, respectively, for AIDS-related death; and 16.0, 17.7, 19.3 and 35.9%, respectively, for new AIDS event/death. In a multivariate Cox's model, higher HIV RNA level, previous AIDS and detection of three CWR (hazard ratio, 5.34; 95% confidence interval, 1.76-16.24) were all significantly associated with increased risk of death, while higher CD4 cell count and use of a new boosted protease inhibitor drug after identifying genotypic resistance were associated with reduced risk. Detection of three CWR was also significantly associated with higher risk of AIDS-related death and new AIDS event/death. CONCLUSIONS: Even in the late era of highly effective antiretroviral treatments, detection of CWR, particularly if extended to all three drug classes is related to poorer clinical outcome and represents a risk-marker of disease progression and death.     

Family occurrence of autoimmune hepatitis: A Danish nationwide registry-based cohort study

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部分非鲍曼不动杆菌耐药性及相关基因分析

目的了解目前非鲍曼不动杆菌临床分离株的耐药现状及耐药基因携带情况。方法随机抽取100株不动杆菌临床分离株,采用分子生物学方法筛选非鲍曼不动杆菌,用E-test方法检测非鲍曼不动杆菌对12种抗生素的耐药性,用PCR方法检测16种相关耐药基因的分布。结果共筛选出17株非鲍曼不动杆菌,7株为多重耐药(41.2%),其中对头孢噻肟的耐药率为100%,对氯霉素、哌拉西林、氨苄西林和氨曲南的耐药率分别为76.5%、76.5%、64.7%和52.9%,对多粘菌素B普遍敏感;检出6种耐药基因分别为ampC、blaTEM、blaPER-1、blaOXA-23-like、blaOXA-58和Int1。结论携带超广谱β-内酰胺酶(ESBLs)基因和blaOXA-23-like基因为非鲍曼不动杆菌对β-内酰胺类和碳青霉烯类抗生素耐药的主要原因。非鲍曼不动杆菌的耐药形势严峻,应加强监测。     

Adverse drug reactions associated with first-line anti-tuberculosis drug regimens.

BACKGROUND: Standard treatment of active tuberculosis (TB) consists of isoniazid (INH), rifampin (RMP), pyrazinamide (PZA) and ethambutol (EMB). Although this regimen is effective in treating active TB, it is associated with many adverse drug reactions (ADRs) and poses a significant challenge to completion of treatment. OBJECTIVES: To examine the incidence of major ADRs and risk factors associated with first-line anti-tuberculosis medications. METHODS: This study evaluated patients receiving treatment for active TB from a population-based database (2000-2005). The nature of the ADRs, likelihood of association with the study medications and severity were evaluated. RESULTS: A total of 1061 patients received treatment, of whom 318 (30%) had at least one major ADR. The overall incidence of all major ADRs was 7.3 events per 100 person-months (95%CI 7.2-7.5): 23.3 (95%CI 23.0-23.7) when on all four first-line drugs, 13.6 (95%CI 13.3-14.0) when on RMP, INH and PZA, and 2.4 (95%CI 2.3-2.6) when on INH and RMP. Adjusted hazard ratio (HR) revealed that combination regimens containing PZA, females, subjects aged 35-59 and >or=60 years, baseline aspartate aminotransferase >or=80 U/l and drug resistance were associated with any major event. CONCLUSIONS: First-line anti-tuberculosis drugs are associated with significant ADRs. There are several risk factors associated with the development of ADRs, including exposure to regimens containing PZA.