Identifying Targets for Antibiotic Use for the Management of Carbapenem-Resistant Acinetobacter baumannii (CRAb) in Hospitals-A Multi-Centre Nonlinear Time-Series Study.

Solutions are needed to inform antimicrobial stewardship (AMS) regarding balancing the access to effective antimicrobials with the need to control antimicrobial resistance. Theoretical and mathematical models suggest a non-linear relationship between antibiotic use and resistance, indicating the existence of thresholds of antibiotic use beyond which resistance would be triggered. It is anticipated that thresholds may vary across populations depending on host, environment, and organism factors. Further research is needed to evaluate thresholds in antibiotic use for a specific pathogen across different settings. The objective of this study is to identify thresholds of population antibiotic use associated with the incidence of carbapenem-resistant Acinetobacter baumannii (CRAb) across six hospital sites in Oman. The study was an ecological, multi-centre evaluation that involved collecting historical antibiotic use and CRAb incidence over the period from January 2015 to December 2019. By using non-linear time-series analysis, we identified different thresholds in the use of third-generation cephalosporins, piperacillin-tazobactam, aminoglycoside, and fluoroquinolones across participating hospitals. The identification of different thresholds emphasises the need for tailored analysis based on modelling data from each hospital. The determined thresholds can be used to set targets for each hospital AMS, providing a balance between access to these antibiotics versus controlling CRAb incidence.

Long-Term Impact of the COVID-19 Pandemic on In-Hospital Antibiotic Consumption and Antibiotic Resistance: A Time Series Analysis (2015-2021).

The coronavirus disease 2019 (COVID-19)-pandemic-related overload of health systems has compromised the application of antimicrobial stewardship (AS) models and infection prevention and control (IPC) programs. We aimed to evaluate the impact of COVID-19 on antimicrobial consumption (AC) and antimicrobial resistance (AMR) in the University Hospital of Modena. A time series analysis with an autoregressive integrated moving average model was conducted from January 2015 to October 2021 to evaluate the AC in the whole hospital and the intensive care unit (ICU), the incidence density (ID) of bloodstream infections (BSIs) due to the main multidrug-resistant organisms, and of C. difficile infections (CDIs). After an initial peak during the COVID-19 period, a decrease in the trend of AC was observed, both at the hospital (CT: -1.104, p = 0.025) and ICU levels (CT: -4.47, p = 0.047), with no significant difference in the single classes. Among the Gram-negative isolates, we observed a significant increase only in the level of BSIs due to carbapenem-susceptible Pseudomonas aeruginosa (CL: 1.477, 95% CI 0.130 to 2.824, p = 0.032). Considering Gram-positive bacteria, an increase in the level of BSIs due to methicillin-resistant Staphylococcus aureus and in the trend of CDIs were observed, though they did not reach statistical significance (CL: 0.72, 95% CI -0.039 to 1.48, p = 0.062; CT: 1.43, 95% CI -0.002 to 2.863, p = 0.051; respectively). Our findings demonstrated that the increases in AMR and AC that appeared in the first COVID-19 wave may be later controlled by restoring IPC and AS programs to pre-epidemic levels. A coordinated healthcare effort is necessary to address the longer-term impact of COVID-19 on AC to avoid irreversible consequences on AMR.

A five-component infection control bundle to permanently eliminate a carbapenem-resistant Acinetobacter baumannii spreading in an intensive care unit.

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) infection outbreaks are difficult to control and sometimes require cohorting of CRAB-positive patients or temporary ward closure for environmental cleaning. We aimed at controlling the deadly 2018 CRAB outbreak in a 12 bed- intensive care unit (ICU) including 9 beds in a 220 m2 open space. We implemented a new multimodal approach without ward closure, cohorting or temporarily limiting admissions. METHODS: A five-component bundle was introduced in 2018 including reinforcement of hand hygiene and sample extension of screening, application of contact precautions to all patients, enhanced environmental sampling and the one-time application of a cycling radical environmental cleaning and disinfection procedure of the entire ICU. The ICU-CRAB incidence density (ID), ICU alcohol-based hand rub consumption and antibiotic use were calculated over a period of 6 years and intervention time series analysis was performed. Whole genome sequencing analysis (WGS) was done on clinical and environmental isolates in the study period. RESULTS: From January 2013, nosocomial ICU-CRAB ID decreased from 30.4 CRAB cases per 1000 patients-days to zero cases per 1000 patients-days. Our intervention showed a significant impact (-2.9 nosocomial ICU-CRAB cases per 1000 bed-days), while no influence was observed for antibiotic and alcohol-based hand rub (AHR) consumption. WGS demonstrated that CRAB strains were clonally related to an environmental reservoir which confirms the primary role of the environment in CRAB ICU spreading. CONCLUSION: A five-component bundle of continuous hand hygiene improvement, extended sampling at screening including the environment, universal contact precautions and a novel cycling radical environmental cleaning and disinfection procedure proved to be effective for permanently eliminating CRAB spreading within the ICU. Cohorting, admission restriction or ICU closure were avoided.

Identification of thresholds in relationships between specific antibiotic use and carbapenem-resistant Acinetobacter baumannii (CRAb) incidence rates in hospitalized patients in Jordan.

BACKGROUND: Antibiotic resistance is a major threat to public health worldwide. The relationship between the intensity of antibiotic use and resistance might not be linear, suggesting that there might be a threshold of antibiotic use, beyond which resistance would be triggered. OBJECTIVES: To identify thresholds in antibiotic use, below which specific antibiotic classes have no significant measurable impact on the incidence of carbapenem-resistant Acinetobacter baumannii (CRAb), but above which their use correlates with an increase in the incidence of CRAb. METHODS: The study took place at a tertiary teaching hospital in Jordan. The study was ecological in nature and was carried out retrospectively over the period January 2014 to December 2019. The outcome time series for this study was CRAb cases. The primary explanatory variables were monthly use of antibiotics and the use of alcohol-based hand rub (ABHR). Non-linear time-series methods were used to identify thresholds in antibiotic use. RESULTS: Non-linear time-series analysis determined a threshold in third-generation cephalosporin and carbapenem use, where the maximum use of third-generation cephalosporins and carbapenems should not exceed 8 DDD/100 occupied bed days (OBD) and 10 DDD/100 OBD, respectively. ABHR had a significant reducing effect on CRAb cases even at lower usage quantities (0.92 L/100 OBD) and had the most significant effect when ABHR exceeded 3.4 L/100 OBD. CONCLUSIONS: The identification of thresholds, utilizing non-linear time-series methods, can provide a valuable tool to inform hospital antibiotic policies through identifying quantitative targets that balance access to effective therapies with control of resistance. Further studies are needed to validate the identified thresholds, through being prospectively adopted as a target for antimicrobial stewardship programmes, and then to evaluate the impact on reducing CRAb incidence.

Author Correction: A nonlinear time-series analysis approach to identify thresholds in associations between population antibiotic use and rates of resistance.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A nonlinear time-series analysis approach to identify thresholds in associations between population antibiotic use and rates of resistance.

Balancing access to antibiotics with the control of antibiotic resistance is a global public health priority. At present, antibiotic stewardship is informed by a 'use it and lose it' principle, in which antibiotic use by the population is linearly related to resistance rates. However, theoretical and mathematical models suggest that use-resistance relationships are nonlinear. One explanation for this is that resistance genes are commonly associated with 'fitness costs' that impair the replication or transmissibility of the pathogen. Therefore, resistant genes and pathogens may only gain a survival advantage where antibiotic selection pressures exceed critical thresholds. These thresholds may provide quantitative targets for stewardship-optimizing the control of resistance while avoiding over-restriction of antibiotics. Here, we evaluated the generalizability of a nonlinear time-series analysis approach for identifying thresholds using historical prescribing and microbiological data from five populations in Europe. We identified minimum thresholds in temporal relationships between the use of selected antibiotics and incidence rates of carbapenem-resistant Acinetobacter baumannii (Hungary), extended-spectrum ß-lactamase-producing Escherichia coli (Spain), cefepime-resistant E. coli (Spain), gentamicin-resistant Pseudomonas aeruginosa (France) and methicillin-resistant Staphylococcus aureus (Northern Ireland) in different epidemiological phases. Using routinely generated data, our approach can identify context-specific quantitative targets for rationalizing population antibiotic use and controlling resistance. Prospective intervention studies that restrict antibiotic consumption are needed to validate these thresholds.

Effect of a national 4C antibiotic stewardship intervention on the clinical and molecular epidemiology of Clostridium difficile infections in a region of Scotland: a non-linear time-series analysis.

BACKGROUND: Whereas many antibiotics increase risk of Clostridium difficile infection through dysbiosis, epidemic C difficile ribotypes characterised by multidrug resistance might depend on antibiotic selection pressures arising from population use of specific drugs. We examined the effect of a national antibiotic stewardship intervention limiting the use of 4C antibiotics (fluoroquinolones, clindamycin, co-amoxiclav, and cephalosporins) and other infection prevention and control strategies on the clinical and molecular epidemiology of C difficile infections in northeast Scotland. METHODS: We did a non-linear time-series analysis and quasi-experimental study to explore ecological determinants of clinical burdens from C difficile infections and ribotype distributions in a health board serving 11% of the Scottish population. Study populations were adults (aged ≥16 years) registered with primary carer providers in the community (mean 455 508 inhabitants) or admitted to tertiary level, district general, or geriatric hospitals (mean 33 049 total admissions per month). A mixed persuasive-restrictive 4C antibiotic stewardship intervention was initiated in all populations on May 1, 2009. Other population-specific interventions considered included limiting indications for macrolide prescriptions, introduction of alcohol-based hand sanitiser, a national hand-hygiene campaign, national auditing and inspections of hospital environment cleanliness, and reminders to reduce inappropriate use of proton-pump inhibitors. The total effect of interventions was defined as the difference between observations and projected scenarios without intervention. Primary outcomes were prevalence density of C difficile infection per 1000 occupied bed-days in hospitals or per 100 000 inhabitant-days in the community. FINDINGS: Between Jan 1, 1997, and Dec 31, 2012, we identified 4885 cases of hospital-onset C difficile infection among 1 289 929 admissions to study hospitals, and a further 1625 cases of community-onset C difficile infection among 455 508 adults registered in primary care. Use of 4C antibiotics was reduced by 50% in both hospitals (mean reduction 193 defined daily doses per 1000 occupied bed-days, 95% CI 45-328, p=0·008) and the community (1·85 defined daily doses per 1000 inhabitant-days, 95% CI 0·23-3·48, p=0·025) during antibiotic stewardship. Falling 4C use predicted rapid declines in multidrug-resistant ribotypes R001 and R027. Hospital-onset C difficile infection prevalence densities were associated with fluoroquinolone, third-generation cephalosporin, macrolides, and carbapenem use, exceeding hospital population specific total use thresholds. Community-onset C difficile infection prevalence density was predicted by recent hospital C difficile infection rates, introduction of mandatory surveillance in individuals older than 65 years, and primary-case use of fluoroquinolones and clindamycin exceeding total use thresholds. Compared with predictions without intervention, C difficile infection prevalence density fell by 68% (mean reduction 1·01 per 1000 occupied bed-days, 0·27-1·76, p=0·008) in hospitals and 45% (0·083, 0·045-0·121 cases per 100 000 inhabitant-days, p<0·0001) in the community, during antibiotic stewardship. We identified no significant effects from other interventions. INTERPRETATION: Limiting population use of 4C antibiotics reduced selective pressures favouring multidrug-resistant epidemic ribotypes and was associated with substantial declines in total C difficile infections in northeast Scotland. Efforts to control C difficile through antibiotic stewardship should account for ribotype distributions and non-linear effects. FUNDING: NHS Grampian Microbiology Endowment Fund.

Effects of national antibiotic stewardship and infection control strategies on hospital-associated and community-associated meticillin-resistant Staphylococcus aureus infections across a region of Scotland: a non-linear time-series study.

BACKGROUND: Restriction of antibiotic consumption to below predefined total use thresholds might remove the selection pressure that maintains antimicrobial resistance within populations. We assessed the effect of national antibiotic stewardship and infection prevention and control programmes on prevalence density of meticillin-resistant Staphylococcus aureus (MRSA) infections across a region of Scotland. METHODS: This non-linear time-series analysis and quasi-experimental study explored ecological determinants of MRSA epidemiology among 1,289,929 hospital admissions and 455,508 adults registered in primary care in northeast Scotland. Interventions included antibiotic stewardship to restrict use of so-called 4C (cephalosporins, co-amoxiclav, clindamycin, and fluoroquinolones) and macrolide antibiotics; a hand hygiene campaign; hospital environment inspections; and MRSA admission screening. Total effects were defined as the difference between scenarios with intervention (observed) and without intervention (predicted from time-series models). The primary outcomes were prevalence density of MRSA infections per 1000 occupied bed days (OBDs) in hospitals or per 10,000 inhabitants per day (IDs) in the community. FINDINGS: During antibiotic stewardship, use of 4C and macrolide antibiotics fell by 47% (mean decrease 224 defined daily doses [DDDs] per 1000 OBDs, 95% CI 154-305, p=0·008) in hospitals and 27% (mean decrease 2·52 DDDs per 1000 IDs, 0·65-4·55, p=0·031) in the community. Hospital prevalence densities of MRSA were inversely related to intensified infection prevention and control, but positively associated with MRSA rates in neighbouring hospitals, importation pressures, bed occupancy, and use of fluoroquinolones, co-amoxiclav, and third-generation cephalosporins, or macrolide antibiotics that exceeded hospital-specific thresholds. Community prevalence density was predicted by hospital MRSA rates and above-threshold use of macrolides, fluoroquinolones, and clindamycin. MRSA prevalence density decreased during antibiotic stewardship by 54% (mean reduction 0·60 per 1000 OBDs, 0·01-1·18, p=0·049) in hospital and 37% (mean reduction 0·017 per 10,000 IDs, 0·004-0·029, p=0·012) in the community. Combined with infection prevention and control measures, MRSA prevalence density was reduced by 50% (absolute difference 0·94 cases per 1000 OBDs, 0·27-1·62, p=0·006) in hospitals and 47% (absolute difference 0·033 cases per 10,000 IDs, 0·018-0·048, p<0·0001) in the community. INTERPRETATION: Alongside infection control measures, removal of key antibiotic selection pressures during a national antibiotic stewardship intervention predicted large and sustained reductions in hospital-associated and community-associated MRSA. FUNDING: NHS Grampian Research & Development Fund.

Turning the tide or riding the waves? Impacts of antibiotic stewardship and infection control on MRSA strain dynamics in a Scottish region over 16 years: non-linear time series analysis.

OBJECTIVES: To explore temporal associations between planned antibiotic stewardship and infection control interventions and the molecular epidemiology of methicillin-resistant Staphylococcus aureus (MRSA). DESIGN: Retrospective ecological study and time-series analysis integrating typing data from the Scottish MRSA reference laboratory. SETTING: Regional hospital and primary care in a Scottish Health Board. PARTICIPANTS: General adult (N=1,051,993) or intensive care (18,235) admissions and primary care registrations (460,000 inhabitants) between January 1997 and December 2012. INTERVENTIONS: Hand-hygiene campaign; MRSA admission screening; antibiotic stewardship limiting use of macrolides and '4Cs' (cephalosporins, coamoxiclav, clindamycin and fluoroquinolones). OUTCOME MEASURES: Prevalence density of MRSA clonal complexes CC22, CC30 and CC5/Other in hospital (isolates/1000 occupied bed days, OBDs) and community (isolates/10,000 inhabitant-days). RESULTS: 67% of all clinical MRSA isolates (10,707/15,947) were typed. Regional MRSA population structure was dominated by hospital epidemic strains CC30, CC22 and CC45. Following declines in overall MRSA prevalence density, CC5 and other strains of community origin became increasingly important. Reductions in use of '4Cs' and macrolides anticipated declines in sublineages with higher levels of associated resistances. In multivariate time-series models (R(2)=0.63-0.94) introduction of the hand-hygiene campaign, reductions in mean length of stay (when >4 days) and bed occupancy (when >74 to 78%) predicted declines in CC22 and CC30, but not CC5/other strains. Lower importation pressures, expanded MRSA admission screening, and reductions in macrolide and third generation cephalosporin use (thresholds for association: 135-141, and 48-81 defined daily doses/1000 OBDs, respectively) were followed by declines in all clonal complexes. Strain-specific associations with fluoroquinolones and clindamycin reflected resistance phenotypes of clonal complexes. CONCLUSIONS: Infection control measures and changes in population antibiotic use were important predictors of MRSA strain dynamics in our region. Strategies to control MRSA should consider thresholds for effects and strain-specific impacts.

Trends in Staphylococcus aureus bacteraemia and impacts of infection control practices including universal MRSA admission screening in a hospital in Scotland, 2006-2010: retrospective cohort study and time-series intervention analysis.

OBJECTIVES: To describe secular trends in Staphylococcus aureus bacteraemia (SAB) and to assess the impacts of infection control practices, including universal methicillin-resistant Staphylococcus aureus (MRSA) admission screening on associated clinical burdens. DESIGN: Retrospective cohort study and multivariate time-series analysis linking microbiology, patient management and health intelligence databases. SETTING: Teaching hospital in North East Scotland. PARTICIPANTS: All patients admitted to Aberdeen Royal Infirmary between 1 January 2006 and 31 December 2010: n=420 452 admissions and 1 430 052 acute occupied bed days (AOBDs). INTERVENTION: Universal admission screening programme for MRSA (August 2008) incorporating isolation and decolonisation. PRIMARY AND SECONDARY MEASURES: Hospital-wide prevalence density, hospital-associated incidence density and death within 30 days of MRSA or methicillin-sensitive Staphylococcus aureus (MSSA) bacteraemia. RESULTS: Between 2006 and 2010, prevalence density of all SAB declined by 41%, from 0.73 to 0.50 cases/1000 AOBDs (p=0.002 for trend), and 30-day mortality from 26% to 14% (p=0.013). Significant reductions were observed in MRSA bacteraemia only. Overnight admissions screened for MRSA rose from 43% during selective screening to >90% within 4 months of universal screening. In multivariate time-series analysis (R(2) 0.45 to 0.68), universal screening was associated with a 19% reduction in prevalence density of MRSA bacteraemia (-0.035, 95% CI -0.049 to -0.021/1000 AOBDs; p<0.001), a 29% fall in hospital-associated incidence density (-0.029, 95% CI -0.035 to -0.023/1000 AOBDs; p<0.001) and a 46% reduction in 30-day mortality (-15.6, 95% CI -24.1% to -7.1%; p<0.001). Positive associations with fluoroquinolone and cephalosporin use suggested that antibiotic stewardship reduced prevalence density of MRSA bacteraemia by 0.027 (95% CI 0.015 to 0.039)/1000 AOBDs. Rates of MSSA bacteraemia were not significantly affected by screening or antibiotic use. CONCLUSIONS: Declining clinical burdens from SAB were attributable to reductions in MRSA infections. Universal admission screening and antibiotic stewardship were associated with decreases in MRSA bacteraemia and associated early mortality. Control of MSSA bacteraemia remains a priority.

Modelling the impact of antibiotic use on antibiotic-resistant Escherichia coli using population-based data from a large hospital and its surrounding community.

OBJECTIVES: To determine the temporal relationship between antibiotic use and incidence of antibiotic-resistant Escherichia coli in both the inpatient and outpatient setting of a large urban area. METHODS: A retrospective observational time-series analysis was performed to evaluate the incidence of non-duplicate clinical isolates of E. coli resistant to ciprofloxacin, trimethoprim/sulfamethoxazole and cefepime from January 2000 through December 2007, combined with a transfer function model of aggregated data on antibiotic use in both settings obtained from the hospital's pharmacy and outpatient billing offices. RESULTS: Ciprofloxacin resistance increased from 6.0% (2000) to 15.4% (2007; P<0.0001) and cefepime resistance from 0.9% (2002) to 3.2% (2007; P=0.01). Trimethoprim/sulfamethoxazole resistance remained stable (23.7%-25.8%). Total antibiotic use increased in both settings, while fluoroquinolone use increased significantly only among outpatients. A temporal effect between fluoroquinolone resistance in community E. coli isolates and outpatient use of ciprofloxacin (immediate effect and time lag 1 month) and moxifloxacin (time lag 4 months) was observed, explaining 51% of the variance over time. The incidence of cefepime resistance in E. coli was correlated with ciprofloxacin use in the inpatient (lag 1 month) and outpatient (lag 4 months) settings and with the use of ceftriaxone (lag 0 month), piperacillin/tazobactam (3 months) and cefepime (3 months) in the hospital (R2=51%). CONCLUSIONS: These results support efforts to reduce prescribing of fluoroquinolones for control of resistant E. coli including extended-spectrum ß-lactamase producers and show the added value of time-series analysis to better understand the interaction between community and hospital antibiotic prescribing and its spill-over effect on antibiotic resistance.

Modelling the impact of antibiotic use and infection control practices on the incidence of hospital-acquired methicillin-resistant Staphylococcus aureus: a time-series analysis.

OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) is a major nosocomial pathogen worldwide. A wide range of factors have been suggested to influence the spread of MRSA. The objective of this study was to evaluate the effect of antimicrobial drug use and infection control practices on nosocomial MRSA incidence in a 426-bed general teaching hospital in Northern Ireland. METHODS: The present research involved the retrospective collection of monthly data on the usage of antibiotics and on infection control practices within the hospital over a 5 year period (January 2000-December 2004). A multivariate ARIMA (time-series analysis) model was built to relate MRSA incidence with antibiotic use and infection control practices. RESULTS: Analysis of the 5 year data set showed that temporal variations in MRSA incidence followed temporal variations in the use of fluoroquinolones, third-generation cephalosporins, macrolides and amoxicillin/clavulanic acid (coefficients = 0.005, 0.03, 0.002 and 0.003, respectively, with various time lags). Temporal relationships were also observed between MRSA incidence and infection control practices, i.e. the number of patients actively screened for MRSA (coefficient = -0.007), the use of alcohol-impregnated wipes (coefficient = -0.0003) and the bulk orders of alcohol-based handrub (coefficients = -0.04 and -0.08), with increased infection control activity being associated with decreased MRSA incidence, and between MRSA incidence and the number of new patients admitted with MRSA (coefficient = 0.22). The model explained 78.4% of the variance in the monthly incidence of MRSA. CONCLUSIONS: The results of this study confirm the value of infection control policies as well as suggest the usefulness of restricting the use of certain antimicrobial classes to control MRSA.

[Expanded-spectrum beta-lactamase-producing strains of E. coli: origin, characteristics and incidence in Southern Alicante (Spain) in the period 1999-2003]. / Cepas de Escherichia coli productoras de betalactamasas de espectro extendido: origen, características e incidencia en el sur de la provincia de Alicante en el período 1999-2003.

INTRODUCTION: In the last years, we have verified the increasing emergence of bacteria, specially Escherichia coli, that produce expanded spectrum beta-lactamases (ESBL), enzymes which confer resistance to all cephalosporins (except cephamycins) and aztreonam. These bacteria are frequently resistant also to non-beta-lactam antibiotics, a fact which poses an important clinical problem. METHODS: Descriptive study of ESBL-producing strains of E. coli isolated in all kind of specimens in two hospitals of Southern Alicante (Spain), throughout a period of 57 months (January 1999 to September 2003), paying a close attention to their origin (outpatients or admitted patients), co-resistance to non beta-lactam antibiotics and evolution of their incidence. RESULTS: Respectively, 3% and 2.25% of E. coli strains isolated in each hospital produce ESBL (3.83% and 2.85% of strains from admitted and 2.74% and 2.1% from outpatients). 30.73% and 24.58% of strains ESBL were isolated in admitted patients. We found in both hospitals much higher percentages of co-resistance to ciprofloxacin, gentamicin and trimetoprim-sulfamethoxazole in ESBL-producing strains. CONCLUSION: The percentage of ESBL-producing E. coli is high in our environment, but it is even more noteworthy its clear trend to increase. It is very remarkable the high percentage of ESBL-producing strains isolated from outpatients. Finally, we emphasize the high percentages of co-resistance to non-beta-lactam antibiotics.

Cepas de Escherichia coli productoras de betalactamasas de espectro extendido: origen, características e incidencia en el sur de la provincia de Alicante en el período 1999-2003 / Expanded-spectrum beta-lactamase-producing strains of E. coli: origin, characteristics and incidence in Southern Alicante (Spain) in the period 1999-2003

INTRODUCCIÓN. En los últimos años observamos la aparición, cada vez más frecuente, de bacterias, y singularmente de Escherichia coli, productoras de betalactamasas de espectro extendido (BLEE), que confieren resistencia a las cefalosporinas (excepto cefamicinas) y aztreonam. Estas bacterias son frecuentemente resistentes también a antibióticos no betalactámicos, lo que plantea un importante problema clínico. MÉTODOS. Estudio descriptivo de las cepas de E. colip roductoras de BLEE aisladas en todo tipo de muestras en dos hospitales del sur de la provincia de Alicante en un período de 57 meses (de enero de 1999 a septiembre de 2003), con especial atención a su origen (intrahospitalario o extrahospitalario), a las corresistencias a antibióticosno betalactámicos y a la evolución cronológica de su incidencia. RESULTADOS. Respectivamente, 3 y 2,25% de las cepas de E. coli aisladas en cada hospital son productoras de BLEE(3,83 y 2,85% de las cepas procedentes de ingresados y 2,74 y 2,1% de las de pacientes ambulatorios). El 30,73y 24,58% de las cepas productoras de BLEE se aislaronen pacientes hospitalizados. En ambos hospitales se encontraron porcentajes de corresistencia a ciprofloxacino, gentamicina y cotrimoxazol muy superiores en cepas productoras de BLEE.CONCLUSIÓN. El porcentaje de cepas de E. coli productoras de BLEE es elevado en nuestro medio, pero es más notable su clara tendencia al incremento. Es reseñable el elevado porcentaje de cepas productoras procedentes del ámbito extrahospitalario. Por último, resaltamos los elevados índices de corresistencia a antibióticos no betalactámicos (AU)

INTRODUCTION. In the last years, we have verified the increasing emergence of bacteria, specially Escherichia coli, that produce expanded spectrum beta-lactamases (ESBL),enzymes which confer resistance to all cephalosporins(except cephamycins) and aztreonam. These bacteria are frequently resistant also to non-beta-lactam antibiotics,a fact wich poses an important clinical problem. METHODS. Descriptive study of ESBL-producing strains of E. coli isolated in all kind of specimens in two hospitals of Southern Alicante (Spain), troughout a period of 57 months (January 1999 to September 2003), paying a close attention to their origin (outpatients or admitted patients), co-resistance to non beta-lactam antibiotics and evolution of their incidence. RESULTS. Respectively, 3% and 2.25% of E. coli strains isolated in each hospital produce ESBL (3.83% and 2.85% of strains from admitted and 2.74% and 2.1% from out patients). 30.73% and 24.58% of strains ESBL were isolated in admitted patients. We found in both hospitals much higher percentages of co-resistance to ciprofloxacin, gentamicin and trimetoprim-sulfamethoxazole in ESBL-producing strains. CONCLUSION. The percentage of ESBL-producing E. coli is high in our environment, but it is even more note worthy its clear trend to increase. It is very remarkable the high percentage of ESBL-producing strains isolated from outpatients. Finally, we emphasize the high percentages of co-resistance to non-beta-lactam antibiotics (AU)

Antimicrobial drug use and methicillin-resistant Staphylococcus aureus, Aberdeen, 1996-2000.

Similar to many hospitals worldwide, Aberdeen Royal Infirmary has had an outbreak of methicillin-resistant Staphylococcus aureus (MRSA). In this setting, the outbreak is attributable to two major clones. The relationships between antimicrobial use and MRSA prevalence were analyzed by time-series analysis. From June 1997 to December 2000, dynamic, temporal relationships were found between monthly %MRSA and previous %MRSA, macrolide use, third-generation cephalosporin use, and fluoroquinolone use. This study suggests that use of antimicrobial drugs to which the MRSA outbreak strains are resistant may be an important factor in perpetuating the outbreak. Moreover, this study confirmed the ecologic effect of antimicrobial drug use (i.e., current antimicrobial use) may have an effect on resistance in future patients. Although these results may not be generalized to other hospitals, they suggest new directions for control of MRSA, which has thus far proved difficult and expensive.

Criteria of time and antibiotic susceptibility in the elimination of duplicates when calculating resistance frequencies.

We studied the effects of various systems of eliminating repeat isolates on the absolute number and susceptibility of Pseudomonas aeruginosa, Acinetobacter baumannii and Staphylococcus aureus isolates over a 2 year period. The criterion of time is objective and reproducible, whereas that of variation in antibiotic susceptibility detects variations in the susceptibility of microorganisms that acquire resistance during treatment, but may be affected by methodological errors in determining the antibiotic susceptibility. These tools are useful in the control of multi-resistant bacteria and enable the true situation regarding antibiotic resistance in each geographical area to be determined.

Relationship between spread of methicillin-resistant Staphylococcus aureus and antimicrobial use in a French university hospital.

The objective of our study was to determine whether antibiotic pressure in the units of a teaching hospital affects the acquisition of methicillin-resistant Staphylococcus aureus (MRSA), independently of the other collective risk factors previously shown to be involved (MRSA colonization pressure, type of hospitalization unit, and care workload). The average incidence of acquisition of MRSA during the 1-year study period was 0.31 cases per 1000 days of hospitalization, and the use of ineffective antimicrobials reached 504.54 daily defined doses (DDDs) per 1000 days of hospitalization. Univariate analysis showed that acquisition of MRSA was significantly correlated with the use of all antimicrobials, as well as correlated with the use of each class of antimicrobial and with colonization pressure. Multivariate analysis with a Poisson regression model showed that the use of antimicrobials was associated with the incidence of acquisition of MRSA, independently of the other variables studied, but it did not allow us to determine the hierarchy of the different antimicrobial classes with respect to the effect.