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1.
PLoS One ; 17(7): e0270893, 2022.
Article in English | MEDLINE | ID: mdl-35857758

ABSTRACT

OBJECTIVES: Data regarding women infected with SARS-CoV-2 during early trimesters are scarce. We aimed to assess preterm birth (PTB) and small-for-gestational-age (SGA) rates in a large and unselected cohort by trimester at infection and overall. DESIGN: A retrospective cohort study including all women with a positive SARS-CoV-2 RT-PCR test during a non-ectopic singleton pregnancy between February 21st 2020 and July 2nd 2021 (N = 2753). Each infected woman was matched to a non-infected pregnant woman by age, last menstruation date, sector, and socioeconomic status. METHODS: Logistic regression was conducted to assess the risks of PTB and SGA including an interaction between group and trimester of infection. Multivariable models included underlying diseases, previous abortions and null parity. Subgroup analyses were conducted on symptomatic infected women and matched non-infected women. RESULTS: A total of 2753 /2789 (98.7%) eligible women that were infected during pregnancy could be matched, among them, 17.4% and 48.4% were infected during the first and third trimesters, respectively. While first and second trimester infections were not associated with PTB (p>0.8), third trimester infections and in particular after 34 weeks of gestation had a greater risk of PTB with adjusted ORs of 2.76 (95% CI 1.63-4.67) and 7.10 (95% CI 2.44-20.61), respectively. PTB risk was further heightened in symptomatic third trimester infections (OR = 4.28, 95% CI 1.94-9.25). SGA risk was comparable between study groups across all trimesters of infection. Pregnancy loss incidence was similar in both groups (adjusted OR = 1.16; 95% CI 0.90-1.50). CONCLUSION: SARS-CoV-2 infection was associated with increased risk of PTB only among women infected during late pregnancy, particularly among symptomatic women.


Subject(s)
COVID-19 , Premature Birth , COVID-19/complications , COVID-19/epidemiology , Cohort Studies , Female , Fetal Growth Retardation , Humans , Infant, Newborn , Pregnancy , Pregnancy Outcome , Premature Birth/epidemiology , Retrospective Studies , SARS-CoV-2
2.
J Clin Med ; 10(18)2021 Sep 21.
Article in English | MEDLINE | ID: mdl-34575394

ABSTRACT

While trends data of osteoarthritis (OA) are accumulating, primarily from Western Europe and the US, a gap persists in the knowledge of OA epidemiology in Middle Eastern populations. This study aimed to explore the prevalence, incidence, correlations, and temporal trends of OA in Israel during 2013-2018, using a nationally representative primary care database. On 31 December 2018, a total of 180,126 OA patients were identified, representing a point prevalence of 115.3 per 1000 persons (95% CI, 114.8-115.8 per 1000 persons). Geographically, OA prevalence was not uniformly distributed, with the Southern and Northern peripheral districts having a higher prevalence than the rest of the Israeli regions. OA incidence increased over time from 7.36 per 1000 persons (95% CI 6.21-7.50 per 1000 persons) in 2013 to 8.23 per 1000 persons (95% CI 8.09-8.38 per 1000 persons) in 2017 (p-value for trend = 0.02). The incidence was lowest in patients under 60 years (in both sexes) and peaked at 60-70 years. In older ages, the incidence leveled off in men and declined in women. The growing risk of OA warrants a greater attention to timely preventive and therapeutic interventions. Further population-based studies in the Middle East are needed to identify modifiable risk factors for timely preventive and therapeutic interventions.

3.
Rheumatol Ther ; 8(3): 1129-1141, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34106448

ABSTRACT

INTRODUCTION: There is limited evidence on the consumption of analgesics in real-world large cohorts of patients with osteoarthritis (OA), especially in those with comorbidities. We aimed to characterize the use of pharmacological analgesic treatments, evaluate standardized comorbidity rates, and assess treatment trends. Our hypotheses were: (1) OA patients generally consume low and inconsistent pharmacological analgesic treatments; (2) analgesic treatment is often non-congruent with comorbidity-related safety concerns. METHODS: The study was carried out at the second largest health maintenance organization in Israel. Members aged 18 years or above who were diagnosed with OA before December 31, 2018, were included. Information was obtained from the members' electronic medical record (EMR) including data on dispensed prescriptions, which were used to estimate analgesic consumption. RESULTS: A total of 180,126 OA patients were included in our analyses; analgesics were dispensed to 64.2% of the patients, with oral NSAIDs and opioids dispensed to 34.1 and 22.9% of the OA population, respectively. Analgesic use increased with time lapsed from OA diagnosis (p < 0.001), up to a median of 59 days covered (IQR, 20-175) after 21 years. Rates of most comorbidities in the OA population were higher compared to the MHS general population. Patients with comorbidities used more NSAIDs and opioids compared to those without them. CONCLUSIONS: Most OA patients use analgesics, usually oral NSAIDs. Analgesic use remains relatively low throughout the years, indicating that many OA patients are not being treated pharmacologically for pain on a regular basis. Despite having higher rates of several comorbidities compared to MHS general population, many OA patients are still treated with analgesics that can be associated with a worsening in comorbidity.

4.
J Antimicrob Chemother ; 76(8): 2182-2185, 2021 07 15.
Article in English | MEDLINE | ID: mdl-33969419

ABSTRACT

BACKGROUND: Hospital-acquired diarrhoea (HAD) and Clostridioides difficile infection (CDI) may be triggered by antibiotic use. OBJECTIVES: To determine the effect of specific antibiotic agents and duration of therapy on the risk of HAD and CDI. PATIENTS AND METHODS: A single-centre retrospective cohort study was conducted between May 2012 and December 2014 in the internal medicine division. HAD was defined based on documentation of diarrhoea in the medical record or an uncancelled C. difficile test in the laboratory database. CDI was diagnosed using a two-step test (initial glutamate dehydrogenase and toxin A/B EIA, with PCR for discrepant results). Outcomes first occurred on hospital Day 4 or later. Treatment with antibiotics and days of therapy were modelled. RESULTS: In 29 063 hospitalizations there were 970 HAD events [incidence rate per 10 000 patient days (IR) = 38.5] and 105 CDI events (IR = 3.9). Any antibiotic treatment increased the risk of HAD [adjusted relative risk (aRR) 2.79; 95% CI 2.27-3.43] and CDI (aRR 5.31; 95% CI 2.23-12.69). Each day of ß-lactam/ß-lactamase inhibitors (ßL/ßLIs), carbapenems, IV glycopeptides and metronidazole increased the risk of HAD. Each day of ßL/ßLIs, third- and fourth-generation cephalosporins and carbapenems increased the risk of CDI by over 2%. CONCLUSIONS: Preventing HAD and CDI should focus on reducing the overall use of antibiotics and shortening antibiotic exposure, rather than focusing on specific agents.


Subject(s)
Clostridioides difficile , Clostridium Infections , Anti-Bacterial Agents/adverse effects , Clostridioides , Clostridium Infections/drug therapy , Clostridium Infections/epidemiology , Cohort Studies , Diarrhea/chemically induced , Diarrhea/drug therapy , Diarrhea/epidemiology , Hospitals , Humans , Retrospective Studies , Risk Factors
5.
Clin Microbiol Infect ; 27(10): 1481-1487, 2021 Oct.
Article in English | MEDLINE | ID: mdl-33588061

ABSTRACT

OBJECTIVES: Compared to cephalosporin-based prophylaxis, ertapenem prophylaxis lowers the risk of surgical site infection among carriers of extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-PEs) undergoing colorectal surgery. We aimed to determine whether ertapenem prophylaxis leads to increased postoperative colonization with carbapenem-resistant Enterobacterales (CREs) and third-generation-cephalosporin-resistant Enterobacterales (3GCR-Es). METHODS: This study was nested within a quality improvement study of prophylaxis for ESBL-PE carriers undergoing colorectal surgery. Patients were screened 4-6 days after surgery for carriage of ESBL-PEs or other 3GCR-Es and CREs. When CREs were detected, pre- and postsurgical clones were compared using Fourier-transform infrared (FT-IR) spectroscopy. RESULTS: The sample consisted of 56 patients who carried ESBL-PEs before surgery and received cefuroxime/metronidazole prophylaxis (Group 1), 66 who carried ESBL-PEs before surgery and received ertapenem (Group 2), and 103 ESBL-PE non-carriers who received cefuroxime/metronidazole prophylaxis (Group 3). CRE carriage was detected postoperatively in one patient (1.5%) in Group 2 versus eight patients (14.3%) in Group 1 (RD -12.8%; 95%CI -22.4% to -3.1%). For seven out of nine patients, preoperative ESBL-PE and postoperative CRE isolates were compared; in five of them, the pre- and postoperative clones were identical. Postoperative 3GCR-E carriage was detected in 37 patients (56.1%) in Group 2 versus 46 patients in Group 1 (82.1%) (aRD -20.7%, 95%CI -37.3% to -4.1%). CONCLUSIONS: Among ESBL-PE carriers undergoing colorectal surgery, detection of short-term postsurgical colonization by CREs and 3GCR-Es was significantly lower among patients who received ertapenem prophylaxis than those who received cephalosporin-metronidazole prophylaxis. Resistance development in a colonizing bacterial clone, rather than carbapenemase acquisition, was the major mechanism of carbapenem resistance.


Subject(s)
Cefuroxime/therapeutic use , Digestive System Surgical Procedures , Enterobacteriaceae Infections , Ertapenem/therapeutic use , Metronidazole/therapeutic use , Anti-Bacterial Agents/therapeutic use , Carbapenems , Cephalosporins/therapeutic use , Colorectal Surgery , Drug Resistance, Bacterial , Enterobacteriaceae Infections/drug therapy , Enterobacteriaceae Infections/epidemiology , Enterobacteriaceae Infections/prevention & control , Humans , Spectroscopy, Fourier Transform Infrared , beta-Lactamases
6.
Clin Infect Dis ; 72(5): 829-835, 2021 03 01.
Article in English | MEDLINE | ID: mdl-32034414

ABSTRACT

BACKGROUND: In 2009, the Israeli Ministry of Health implemented in post-acute care hospitals (PACHs) a process of discontinuing carbapenem-resistant Enterobacteriaceae (CRE) carrier status. We evaluated the policy's impact on isolation-days, CRE prevalence among known carriers who had completed clearance testing, and CRE acquisition among noncarriers. METHODS: This retrospective study summarized findings from all 15 PACHs in 2009-2017. CRE carriers were considered cleared and removed from contact isolation after 2 rectal cultures negative for CRE and polymerase chain reaction negative for carbapenemases. Data sources included routine surveillance and 4 point prevalence surveys conducted from 2011 to 2017. RESULTS: During the study period, 887 of 6101 CRE carriers (14.5%) completed clearance testing. From 2013 to 2016, the percentage of patient-days in CRE isolation decreased from 9.4% to 3.9% (P = .008). In all surveys combined, there were 819 known CRE carriers; 411 (50%) had completed clearance testing. Of these, 11.4% (47/411) were CRE positive in the survey. At the ward level, the median percentage of patients with no CRE history who were positive on survey decreased from 11.3% in 2011 to 0% in 2017 (P < .001). We found no ward-level correlation between the proportion of carriers who completed clearance and new acquisitions (ρ = 0.02, P = .86). CONCLUSIONS: A process for discontinuing CRE carrier status in PACHs led to a significant reduction in the percentage of patient-days in contact isolation without increasing CRE acquisitions among noncarriers.


Subject(s)
Carbapenem-Resistant Enterobacteriaceae , Cross Infection , Enterobacteriaceae Infections , Anti-Bacterial Agents/therapeutic use , Cross Infection/epidemiology , Cross Infection/prevention & control , Enterobacteriaceae Infections/drug therapy , Enterobacteriaceae Infections/epidemiology , Enterobacteriaceae Infections/prevention & control , Hospitals , Humans , Israel/epidemiology , Policy , Retrospective Studies , Subacute Care
7.
Euro Surveill ; 25(23)2020 06.
Article in English | MEDLINE | ID: mdl-32553060

ABSTRACT

BackgroundThe spread of antimicrobial resistance (AMR) is of worldwide concern. Public health policymakers and pharmaceutical companies pursuing antibiotic development require accurate predictions about the future spread of AMR.AimWe aimed to identify and model temporal and geographical patterns of AMR spread and to predict future trends based on a slow, intermediate or rapid rise in resistance.MethodsWe obtained data from five antibiotic resistance surveillance projects spanning the years 1997 to 2015. We aggregated the isolate-level or country-level data by country and year to produce country-bacterium-antibiotic class triads. We fitted both linear and sigmoid models to these triads and chose the one with the better fit. For triads that conformed to a sigmoid model, we classified AMR progression into one of three characterising paces: slow, intermediate or fast, based on the sigmoid slope. Within each pace category, average sigmoid models were calculated and validated.ResultsWe constructed a database with 51,670 country-year-bacterium-antibiotic observations, grouped into 7,440 country-bacterium-antibiotic triads. A total of 1,037 triads (14%) met the inclusion criteria. Of these, 326 (31.4%) followed a sigmoid (logistic) pattern over time. Among 107 triads for which both sigmoid and linear models could be fit, the sigmoid model was a better fit in 84%. The sigmoid model deviated from observed data by a median of 6.5%; the degree of deviation was related to the pace of spread.ConclusionWe present a novel method of describing and predicting the spread of antibiotic-resistant organisms.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacterial Infections/drug therapy , Drug Resistance, Bacterial , Datasets as Topic , Humans , Microbial Sensitivity Tests , Models, Theoretical , Predictive Value of Tests
8.
Isr J Health Policy Res ; 9(1): 21, 2020 05 01.
Article in English | MEDLINE | ID: mdl-32357941

ABSTRACT

BACKGROUND: Elderly bedridden patients with dementia (EBRPD) are a growing segment of the population. We aimed to describe acute care hospitalization of EBRPD in internal medicine wards: the prevalence of EBRPD, their impact on hospital resources and hospital ecology, one-year survival, and one-year readmission-free survival. METHODS: The study setting was the internal medicine division of one tertiary care hospital in Israel. We conducted a point-prevalence survey to measure the prevalence of EBRPD and the prevalence of multidrug-resistant organism (MDRO) carriage. We also conducted a retrospective chart review of EBRPD who were hospitalized in the internal medicine division in order to assess resource use, survival, and readmission. RESULTS: In the point prevalence surveys (N = 1667 patients), EBRPD comprised 24.3% of patients and 59.0% of mechanically ventilated patients. EBRPD were twice as likely to be colonized or infected by MDROs as other patients (39.3% vs. 18%, p < 0.001); thus, 41% of MDRO carriers during the survey days were EBRPD. In the retrospective study (N = 517 EBRPD), 80% of EBRPD received antibiotics; on average, they received an antibiotic on 87.7% of their hospital days. One-year survival was 35.6% and one-year readmission-free survival was 16.4%. CONCLUSIONS: Acute care hospitalization of EBRPD accounted for a high proportion of bed occupancy and ventilator use in internal medicine wards. EBRPD significantly increase the potential for MDRO transmission. Policymakers should seek alternatives to acute care hospitalization for EBRPD.


Subject(s)
Bedridden Persons/statistics & numerical data , Dementia/therapy , Patients' Rooms/statistics & numerical data , Aged , Aged, 80 and over , Cross-Sectional Studies , Dementia/complications , Female , Health Resources , Humans , Israel , Male , Middle Aged , Patients' Rooms/organization & administration , Prevalence , Retrospective Studies
9.
Clin Infect Dis ; 70(9): 1891-1897, 2020 04 15.
Article in English | MEDLINE | ID: mdl-31613316

ABSTRACT

BACKGROUND: Carriers of extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-PE) who receive cephalosporin-based prophylaxis have twice the risk of surgical site infection (SSI) following colorectal surgery as noncarriers. We tested whether ESBL-PE screening and personalized prophylaxis with ertapenem reduces SSI risk among carriers. METHODS: We conducted a prospective nonrandomized, nonblinded, interventional study in 3 hospitals in Israel, Switzerland, and Serbia. Patients were screened for ESBL-PE carriage before elective colorectal surgery. During the baseline phase, departmental guidelines advised prophylaxis with a cephalosporin plus metronidazole. In the intervention phase, guidelines were changed for ESBL-PE carriers to receive ertapenem. The primary outcome was any type of SSI within 30 days. We calculated adjusted risk differences (ARDs) following logistic regression. RESULTS: The intention-to-treat analysis compared 209 ESBL-PE carriers in the baseline phase to 269 in the intervention phase. SSI rates were 21.5% and 17.5%, respectively (ARD, -4.7% [95% confidence interval {CI}, -11.8% to 2.4%]). Unplanned crossover was high (15%), so to assess efficacy we performed an as-treated analysis comparing 247 patients who received cephalosporin-based prophylaxis with 221 who received ertapenem. SSI rates were 22.7% and 15.8%, respectively (ARD, -7.7% [95% CI, -14.6% to -.8%]), and rates of SSI caused by ESBL-PE were 6.5% and 0.9%, respectively (ARD, -5.6% [95% CI, -8.9% to -2.3%]). There was no significant difference in the rate of deep SSI. The number needed to treat to prevent 1 SSI in ESBL-PE carriers was 13. CONCLUSIONS: Screening for ESBL-PE carriage before colorectal surgery and personalizing prophylaxis for carriers is efficacious in reducing SSI.


Subject(s)
Colorectal Surgery , Enterobacteriaceae Infections , Anti-Bacterial Agents/therapeutic use , Colorectal Surgery/adverse effects , Enterobacteriaceae , Enterobacteriaceae Infections/epidemiology , Enterobacteriaceae Infections/prevention & control , Ertapenem , Humans , Israel , Prospective Studies , Switzerland , beta-Lactamases
10.
Infect Control Hosp Epidemiol ; 40(10): 1188-1190, 2019 10.
Article in English | MEDLINE | ID: mdl-31379306

ABSTRACT

Patients with carbapenem-resistant Acinetobacter baumannii-positive clinical cultures during a prior hospitalization were screened using high sensitivity methods upon first readmission. Of 38 patients, 31.6% screened positive; 42% screened positive within 2 months from discharge, and 14% screened positive more than 5 months from discharge. Carriage was persistent up to 285 days.


Subject(s)
Acinetobacter Infections/diagnosis , Acinetobacter baumannii/isolation & purification , Carrier State/diagnosis , Drug Resistance, Bacterial , Patient Readmission/statistics & numerical data , Acinetobacter Infections/microbiology , Acinetobacter baumannii/drug effects , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , Carbapenems/therapeutic use , Carrier State/microbiology , Female , Humans , Israel , Kaplan-Meier Estimate , Male , Middle Aged
11.
Clin Infect Dis ; 68(10): 1699-1704, 2019 05 02.
Article in English | MEDLINE | ID: mdl-30204851

ABSTRACT

BACKGROUND: Antibiotic prophylaxis that covers enteric pathogens is essential in preventing surgical site infections (SSIs) after colorectal surgery. Current prophylaxis regimens do not cover extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE). We aimed to determine whether the risk of SSI following colorectal surgery is higher in ESBL-PE carriers than in noncarriers. METHODS: We conducted a prospective cohort study of patients who underwent elective colorectal surgery in 3 hospitals in Israel, Switzerland, and Serbia between 2012 and 2017. We included patients who were aged ≥18 years, were screened for ESBL-PE carriage before surgery, received routine prophylaxis with a cephalosporin plus metronidazole, and did not have an infection at the time of surgery. The exposed group was composed of ESBL-PE-positive patients. The unexposed group was a random sample of ESBL-PE-negative patients. We collected data on patient and surgery characteristics and SSI outcomes. We fit logistic mixed effects models with study site as a random effect. RESULTS: A total of 3600 patients were screened for ESBL-PE; 13.8% were carriers SSIs occurred in 55/220 carriers (24.8%) and 49/440 noncarriers (11.1%, P < .001). In multivariable analysis, ESBL-PE carriage more than doubled the risk of SSI (odds ratio [OR], 2.36; 95% confidence interval [CI], 1.50-3.71). Carriers had higher risk of deep SSI (OR, 2.25; 95% CI, 1.27-3.99). SSI caused by ESBL-PE occurred in 7.2% of carriers and 1.6% of noncarriers (OR, 4.23; 95% CI, 1.70-10.56). CONCLUSIONS: ESBL-PE carriers who receive cephalosporin-based prophylaxis are at increased risk of SSI following colorectal surgery.


Subject(s)
Antibiotic Prophylaxis , Carrier State/microbiology , Colorectal Surgery/adverse effects , Enterobacteriaceae Infections/etiology , Surgical Wound Infection/microbiology , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/adverse effects , Carrier State/prevention & control , Cephalosporins/administration & dosage , Cephalosporins/adverse effects , Enterobacteriaceae/drug effects , Enterobacteriaceae/enzymology , Enterobacteriaceae Infections/prevention & control , Feces/microbiology , Female , Humans , Israel , Male , Middle Aged , Prospective Studies , Risk Factors , Serbia , Surgical Wound Infection/prevention & control , Switzerland , beta-Lactamases
12.
Clin Infect Dis ; 68(6): 964-971, 2019 03 05.
Article in English | MEDLINE | ID: mdl-29986007

ABSTRACT

BACKGROUND: Long-term care facilities (LTCFs) are a major reservoir of carbapenem-resistant Enterobacteriaceae (CRE) in healthcare facilities, contributing to rapid regional dissemination of CRE. METHODS: In 2008, The Israeli National Center for Infection Control (NCIC) initiated a coordinated, comprehensive intervention in Israel's LTCFs, encompassing approximately 25000 beds in over 300 institutions. The intervention included implementation of population-tailored contact precautions and early detection of carriers. The NCIC established a real-time repository of all CRE carriers and events of acquisition, supervised information exchange between healthcare facilities and directed intervention at the institutional level during local outbreaks. CRE incidence was determined based on detection of CRE, either during LTFC stay or on admission to another facility. Prevalence was determined by a series of 5 cross-sectional surveys commenced between 2008 and 2015. RESULTS: From January 2009 through December 2015, 5265 patients acquired CRE in LTCFs. During the study period, incidence of acquisition declined in all facility types, to approximately 50% of the baseline (P < .001). The number of skilled nursing facilities and nursing homes experiencing ≥ 5 CRE acquisitions annually decreased from 35 to 11 during this period. The point prevalence of newly detected CRE carriage in post-acute care hospitals decreased from 12.3% in the survey commenced in 2008 to 0.8% in that begun in 2015 (P < .001). CONCLUSIONS: A national, coordinated intervention resulted in a sustained decrease in CRE incidence and prevalence in LTCFs. These results support the assumption that centrally coordinated intervention is an essential public health tool in reducing CRE in healthcare facilities.


Subject(s)
Carbapenem-Resistant Enterobacteriaceae , Cross Infection/epidemiology , Cross Infection/microbiology , Enterobacteriaceae Infections/epidemiology , Enterobacteriaceae Infections/microbiology , Health Facilities , Enterobacteriaceae Infections/drug therapy , Enterobacteriaceae Infections/prevention & control , Hospitals , Humans , Incidence , Israel/epidemiology , Long-Term Care , Nursing Homes , Prevalence , Skilled Nursing Facilities
13.
Lancet Glob Health ; 6(9): e969-e979, 2018 09.
Article in English | MEDLINE | ID: mdl-30103998

ABSTRACT

BACKGROUND: The number of infections caused by resistant organisms is largely unknown. We estimated the number of infections worldwide that are caused by the WHO priority pathogens third-generation cephalosporin-resistant and carbapenem-resistant Escherichia coli and Klebsiella pneumoniae. METHODS: We calculated a uniform weighted mean incidence of serious infections caused by antibiotic-susceptible E coli and K pneumoniae using data from 17 countries. Using this uniform incidence, as well as population sizes and country-specific resistance levels, we estimated the number of infections caused by third-generation cephalosporin-resistant and carbapenem-resistant E coli and K pneumoniae in 193 countries in 2014. We also calculated interval estimates derived from changing the fixed incidence of susceptible infections to 1 SD below and above the weighted mean. We compared an additive model with combination models in which resistant infections were replaced by susceptible infections. We distinguished between higher-certainty regions (those with good-quality data sources for resistance levels and resistance ≤30%), moderate-certainty regions (those with good-quality data sources for resistance levels and including some countries with resistance >30%), and low-certainty regions (those in which good-quality data sources for resistance levels were unavailable for countries comprising at least 20% of the region's population, regardless of resistance level). FINDINGS: Using the additive model, we estimated that third-generation cephalosporin-resistant E coli and K pneumoniae caused 6·4 million (interval estimate 3·5-9·2) bloodstream infections and 50·1 million (27·5-72·8) serious infections in 2014; estimates were 5·5 million (3·0-7·9) bloodstream infections and 43·1 million (23·6-62·2) serious infections in the 25% replacement model, 4·6 million (2·5-6·6) bloodstream infections and 36·0 million (19·7-52·2) serious infections in the 50% replacement model, and 3·7 million (2·0-5·3) bloodstream infections and 28·9 million (15·8-41·9) serious infections in the 75% replacement model. Carbapenem-resistant strains caused 0·5 million (0·3-0·7) bloodstream infections and 3·1 million (1·8-4·5) serious infections based on the additive model, 0·5 million (0·3-0·7) bloodstream infections and 3·0 million (1·7-4·3) serious infections based on the 25% replacement model, 0·4 million (0·2-0·6) bloodstream infections and 2·8 million (1·6-4·1) serious infections based on the 50% replacement model, and 0·4 million (0·2-0·6) bloodstream infections and 2·7 million (1·5-3·8) serious infections based on the 75% replacement model. INTERPRETATION: To our knowledge, this study is the first to report estimates of the global number of infections caused by antibiotic-resistant priority pathogens. Uncertainty stems from scant data on resistance levels from low-income and middle-income countries and insufficient knowledge regarding resistance dynamics when resistance is high. FUNDING: Innovative Medicines Initiative.


Subject(s)
Anti-Bacterial Agents/pharmacology , Bacterial Infections/epidemiology , Bacterial Infections/microbiology , Drug Resistance, Multiple, Bacterial , Escherichia coli/drug effects , Global Health/statistics & numerical data , Klebsiella pneumoniae/drug effects , Carbapenems/pharmacology , Cephalosporin Resistance , Cephalosporins/pharmacology , Humans , Models, Statistical , World Health Organization
14.
PLoS One ; 13(5): e0197111, 2018.
Article in English | MEDLINE | ID: mdl-29758063

ABSTRACT

Extensive antibiotic use over the years has led to the emergence and spread of antibiotic resistant bacteria (ARB). Antibiotic resistance poses a major threat to public health since for many infections antibiotic treatment is no longer effective. Hospitals are focal points for ARB spread. Antibiotic use in hospitals exerts selective pressure, accelerating the spread of ARB. We used an agent-based model to explore the impact of antibiotics on the transmission dynamics and to examine the potential of stewardship interventions in limiting ARB spread in a hospital. Agents in the model consist of patients and health care workers (HCW). The transmission of ARB occurs through contacts between patients and HCW and between adjacent patients. In the model, antibiotic use affects the risk of transmission by increasing the vulnerability of susceptible patients and the contagiousness of colonized patients who are treated with antibiotics. The model shows that increasing the proportion of patients receiving antibiotics increases the rate of acquisition non-linearly. The effect of antibiotics on the spread of resistance depends on characteristics of the antibiotic agent and the density of antibiotic use. Antibiotic's impact on the spread increases when the bacterial strain is more transmissible, and decreases as resistance prevalence rises. The individual risk for acquiring ARB increases in parallel with antibiotic density both for patients treated and not treated with antibiotics. Antibiotic treatment in the hospital setting plays an important role in determining the spread of resistance. Interventions to limit antibiotic use have the potential to reduce the spread of resistance, mainly by choosing an agent with a favorable profile in terms of its impact on patient's vulnerability and contagiousness. Methods to measure these impacts of antibiotics should be developed, standardized, and incorporated into drug development programs and approval packages.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacterial Infections , Drug Resistance, Bacterial , Infection Control , Models, Biological , Bacterial Infections/epidemiology , Bacterial Infections/prevention & control , Bacterial Infections/transmission , Female , Humans , Iatrogenic Disease/epidemiology , Iatrogenic Disease/prevention & control , Male
15.
Microb Drug Resist ; 23(5): 660-665, 2017 Jul.
Article in English | MEDLINE | ID: mdl-27828758

ABSTRACT

Our objectives were to establish a methodology for surveillance of ciprofloxacin-resistant Enterobacteriaceae and gentamicin-resistant Enterobacteriaceae (CPRE and GNRE, respectively) in cattle and to study the prevalence and risk factors for carriage of these bacteria in a national survey. This was a point prevalence study conducted from July to October 2013 in Israel. Stool samples were collected from 1,226 cows in 123 sections of 40 farms of all production types. The number of CPRE- and GNRE-positive cows was highest in quarantine stations and fattening farms and was lowest in pasture farms (p < 0.01). The number of CPRE- and GNRE-positive cows was lowest in dairy farm sections containing adult cows (>25 months) and highest in calves (<4 months) (p < 0.001). In bivariate analysis, other variables that were significant risk factors for CPRE and GNRE carriage included fewer troughs, crowding, lack of manure cleaning, and recent arrival of new calves. Antimicrobial prophylaxis was given almost exclusively to calves and was associated with a higher prevalence of carriers (p < 0.001). Compared to the use of nonselective media (MacConkey agar alone), the use of selective media (MacConkey agar with 10 µg/ml of ciprofloxacin or 5 µg/ml of gentamicin) increased the sensitivity of screening for CPRE and GNRE by 6.6- and 13.5-fold, respectively. CPRE and GNRE were identified in 609 (49.7%) and 840 (68.5%) samples, respectively. This study provides novel data regarding both the epidemiology of CPRE and GNRE carriage in livestock and the microbiological methodology for their surveillance.


Subject(s)
Carrier State/epidemiology , Cattle Diseases/epidemiology , Ciprofloxacin/pharmacology , Drug Resistance, Multiple, Bacterial/genetics , Enterobacteriaceae Infections/veterinary , Enterobacteriaceae/genetics , Gentamicins/pharmacology , Age Factors , Animal Husbandry , Animals , Anti-Bacterial Agents/pharmacology , Carrier State/microbiology , Cattle , Cattle Diseases/drug therapy , Cattle Diseases/microbiology , Dairying , Enterobacteriaceae/drug effects , Enterobacteriaceae/isolation & purification , Enterobacteriaceae Infections/drug therapy , Enterobacteriaceae Infections/epidemiology , Enterobacteriaceae Infections/microbiology , Farms , Feces/microbiology , Female , Israel/epidemiology , Male , Microbial Sensitivity Tests , Prevalence , Risk Factors
16.
Infect Control Hosp Epidemiol ; 37(10): 1219-25, 2016 10.
Article in English | MEDLINE | ID: mdl-27452597

ABSTRACT

OBJECTIVE Carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) are extremely drug-resistant pathogens. Screening of contacts of newly identified CP-CRE patients is an important step to limit further transmission. We aimed to determine the risk factors for CP-CRE acquisition among patients exposed to a CP-CRE index patient. METHODS A matched case-control study was performed in a tertiary care hospital in Israel. The study population was comprised of patients who underwent rectal screening for CP-CRE following close contact with a newly identified CP-CRE index patient. Cases were defined as positive tests for CP-CRE. For each case patient, 2 matched controls were randomly selected from the pool of contacts who tested negative for CP-CRE following exposure to the same index case. Bivariate and multivariate analyses were conducted using conditional logistic regression. RESULTS In total, 53 positive contacts were identified in 40 unique investigations (896 tests performed on 735 contacts) between October 6, 2008, and June 7, 2012. bla KPC was the only carbapenemase identified. In multivariate analysis, risk factors for CP-CRE acquisition among contacts were (1) contact with an index patient for ≥3 days (odds ratio [OR], 9.8; 95% confidence interval [CI], 2.0-48.9), (2) mechanical ventilation (OR, 4.1; 95% CI, 1.4-11.9), and (3) carriage or infection with another multidrug-resistant organism (MDRO; OR, 2.6; 95% CI, 1.0-7.1). Among patients who received antibiotics, cephalosporins were associated with a lower risk of acquisition. CONCLUSIONS Patient characteristics (ventilation and carriage of another MDRO) as well as duration of contact are risk factors for CP-CRE acquisition among contacts. The role of cephalosporins requires further study. Infect Control Hosp Epidemiol 2016;1-7.


Subject(s)
Carbapenem-Resistant Enterobacteriaceae/isolation & purification , Carrier State/microbiology , Cross Infection/microbiology , Cross Infection/transmission , Enterobacteriaceae Infections/transmission , Aged , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , Bacterial Proteins , Case-Control Studies , Cephalosporins/therapeutic use , Cross Infection/epidemiology , Enterobacteriaceae Infections/epidemiology , Feces/microbiology , Female , Humans , Israel/epidemiology , Logistic Models , Male , Middle Aged , Respiration, Artificial , Risk Factors , Tertiary Care Centers , beta-Lactamases
18.
J Clin Microbiol ; 53(11): 3515-21, 2015 11.
Article in English | MEDLINE | ID: mdl-26311861

ABSTRACT

Our objectives were to study the prevalence, risk factors for carriage, and transmission dynamics of extended-spectrum-ß-lactamase (ESBL)-producing Enterobacteriaceae (ESBLPE) in a national survey of cattle. This was a point prevalence study conducted from July to October 2013 in Israel. Stool samples were collected from 1,226 cows in 123 sections on 40 farms of all production types. ESBLPE were identified in 291 samples (23.7%): 287 contained Escherichia coli and 4 contained Klebsiella pneumoniae. The number of ESBLPE-positive cows was the highest in quarantine stations and on fattening farms and was the lowest on pasture farms (P = 0.03). The number of ESBLPE-positive cows was the lowest in sections containing adult cows (age, >25 months) and highest in sections containing calves (age, <4 months) (P < 0.001). Infrastructure variables that were significant risk factors for ESBLPE carriage included crowding, a lack of manure cleaning, and a lack of a cooling (P < 0.001 for each), all of which were more common in sections containing calves. Antimicrobial prophylaxis was given almost exclusively to calves and was associated with a high number of ESBLPE carriers (P < 0.001). The 287 E. coli isolates were typed into 106 repetitive extragenic palindromic (REP)-PCR types and mostly harbored blaCTX-M-1 or blaCTX-M-9 group genes. The isolates on the six farms with ≥15 isolates of ESBLPE were of 4 to 7 different REP-PCR types, with one dominant type being harbored by about half of the isolates. Fourteen types were identified on more than one farm, with only six of the farms being adjacent to each other. The prevalence of ESBLPE carriage is high in calves in cowsheds where the use of antimicrobial prophylaxis is common. ESBLPE disseminate within cowsheds mainly by clonal spread, with limited intercowshed transmission occurring.


Subject(s)
Drug Resistance, Multiple, Bacterial/genetics , Escherichia coli Infections/veterinary , Escherichia coli/genetics , Klebsiella Infections/veterinary , Klebsiella pneumoniae/genetics , beta-Lactamases/genetics , Animals , Anti-Bacterial Agents/pharmacology , Cattle , Escherichia coli/classification , Escherichia coli/drug effects , Escherichia coli/isolation & purification , Escherichia coli Infections/epidemiology , Escherichia coli Infections/transmission , Feces/microbiology , Female , Israel/epidemiology , Klebsiella Infections/epidemiology , Klebsiella Infections/transmission , Klebsiella pneumoniae/classification , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/isolation & purification , Microbial Sensitivity Tests , Molecular Typing , Polymerase Chain Reaction , beta-Lactams/pharmacology
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