Carlos R. V. Kiffer

A spatial approach for the epidemiology of antibiotic use and resistance in community-based studies: the emergence of urban clusters of Escherichia coli quinolone resistance in Sao Paulo, Brasil

BackgroundPopulation antimicrobial use may influence resistance emergence. Resistance is an ecological phenomenon due to potential transmissibility. We investigated spatial and temporal patterns of ciprofloxacin (CIP) population consumption related to E. coli resistance emergence and dissemination in a major Brazilian city. A total of 4,372 urinary tract infection E. coli cases, with 723 CIP resistant, were identified in 2002 from two outpatient centres. Cases were address geocoded in a digital map. Raw CIP consumption data was transformed into usage density in DDDs by CIP selling points influence zones determination. A stochastic model coupled with a Geographical Information System was applied for relating resistance and usage density and for detecting city areas of high/low resistance risk.ResultsE. coli CIP resistant cluster emergence was detected and significantly related to usage density at a level of 5 to 9 CIP DDDs. There were clustered hot-spots and a significant global spatial variation in the residual resistance risk after allowing for usage density.ConclusionsThere were clustered hot-spots and a significant global spatial variation in the residual resistance risk after allowing for usage density. The usage density of 5-9 CIP DDDs per 1,000 inhabitants within the same influence zone was the resistance triggering level. This level led to E. coli resistance clustering, proving that individual resistance emergence and dissemination was affected by antimicrobial population consumption.

Pharmacodynamic evaluation of commonly prescribed oral antibiotics against respiratory bacterial pathogens

BackgroundUpper and lower respiratory tract infections (RTIs) account for a substantial portion of outpatient antibiotic utilization. However, the pharmacodynamic activity of commonly used oral antibiotic regimens has not been studied against clinically relevant pathogens. The objective of this study was to assess the probability of achieving the requisite pharmacodynamic exposure for oral antibacterial regimens commonly prescribed for RTIs in adults against bacterial isolates frequently involved in these processes (S. pneumoniae, H. influenzae, and M. catharralis).MethodsUsing a 5000-subject Monte Carlo simulation, the cumulative fractions of response (CFR), (i.e., probabilities of achieving requisite pharmacodynamic targets) for the most commonly prescribed oral antibiotic regimens, as determined by a structured survey of medical prescription patterns, were assessed against local respiratory bacterial isolates from adults in São Paulo collected during the same time period. Minimal inhibitory concentration (MIC) of 230 isolates of Streptococcus pneumoniae (103), Haemophilus influenzae (98), and Moraxella catharralis (29) from a previous local surveillance were used.ResultsThe most commonly prescribed antibiotic regimens were azithromycin 500 mg QD, amoxicillin 500 mg TID, and levofloxacin 500 mg QD, accounting for 58% of the prescriptions. Varied doses of these agents, plus gatifloxacin, amoxicillin-clavulanate, moxifloxacin, and cefaclor made up the remaining regimens. Utilizing aggressive pharmacodynamic exposure targets, the only regimens to achieve greater than 90% CFR against all three pathogens were amoxicillin/amoxicillin-clavulanate 500 mg TID (> 91%), gatifloxacin 400 mg QD (100%), and moxifloxacin 400 mg QD (100%). Considering S. pneumoniae isolates alone, azithromycin 1000 mg QD also achieved greater than 90% CFR (91.3%).ConclusionsThe only regimens to achieve high CFR against all three pathogen populations in both scenarios were gatifloxacin 400 mg QD, moxifloxacin 400 mg QD, and amoxicillin-clavulanate 500 mg TID. These data suggest the need for reconsideration of empiric antibiotic regimen selection among adult patients with RTIs in the São Paulo area. Additionally, this type of study could be used to optimize prescribing patterns in specific regions in light of emerging resistance.

Structure for prevention of health care–associated infections in Brazilian hospitals: A countrywide study

BACKGROUND Minimal structure is required for effective prevention of health care-associated infection (HAI). The objective of this study was to evaluate the structure for prevention of HAI in a sample of Brazilian hospitals. METHODS This was a cross-sectional study from hospitals in 5 Brazilian regions (n = 153; total beds: 13,983) classified according to the number of beds; 11 university hospitals were used as reference for comparison. Trained nurses carried out the evaluation by using structured forms previously validated. The evaluation of conformity index (CI) included elements of structure of the Health Care-Associated Prevention and Control Committee (HAIPCC), hand hygiene, sterilization, and laboratory of microbiology. RESULTS The median CI for the HAIPCC varied from 0.55-0.94 among hospital categories. Hospitals with >200 beds had the worst ratio of beds to sinks (3.9; P < .001). Regarding alcoholic product for handrubbing, the worst ratio of beds to dispensers was found in hospitals with <50 beds (6.4) compared with reference hospitals (3.3; P < .001). The CI for sterilization services showed huge variation ranging from 0.0-1.00. Reference hospitals were more likely to have their own laboratory of microbiology than other hospitals. CONCLUSION This study highlights the need for public health strategies aiming to improve the structure for HAI prevention in Brazilian hospitals.

A space–time model for carbapenemase-producing Klebsiella pneumoniae (KPC) cluster quantification in a high-complexity hospital

A retrospective space-time permutation model with non-Euclidean distance criteria was applied within a high-complexity hospital setting to quantitatively explore cluster patterns of 273 patients infected with or colonized by carbapenemase-producing Klebsiella pneumoniae during 4 years. Results were compared to standard nosocomial active-surveillance methods. Two clusters were identified in the period, suggesting that space-time strategies for cluster quantification within confined environments may be useful.

Pharmacodynamic profiling of commonly prescribed antimicrobial drugs against Escherichia coli isolates from urinary tract

Since antimicrobial resistance among uropathogens against current first line agents has affected the management of severe urinary tract infection, we determined the likelihood that antibiotic regimens achieve bactericidal pharmacodynamic exposures using Monte Carlo simulation for five antimicrobials (ciprofloxacin, ceftriaxone, piperacillin/tazobactam, ertapenem, and meropenem) commonly prescribed as initial empirical treatment of inpatients with severe community acquired urinary tract infections. Minimum inhibitory concentration determination by Etest was performed for 205 Brazilian community urinary tract infection Escherichia coli strains from 2008 to 2012 and 74 E. coli bloodstream strains recovered from a surveillance study. Pharmacodynamic exposure was modeled via a 5000 subject Monte Carlo simulation. All isolates were susceptible to ertapenem and meropenem. Piperacillin/tazobactam, ceftriaxone and ciprofloxacin showed 100%, 97.5% and 83.3% susceptibility among outpatient isolates and 98.6%, 75.7% and 64.3% among inpatient isolates, respectively. Against outpatient isolates, all drugs except ciprofloxacin (82.7% in aggressive and 77.6% in conservative scenarios) achieved high cumulative fraction of response: carbapenems and piperacillin/tazobactam cumulative fraction of responses were close to 100%, and ceftriaxone cumulative fraction of response was 97.5%. Similar results were observed against inpatients isolates for carbapenems (100%) and piperacillin/tazobactam (98.4%), whereas ceftriaxone achieved only 76.9% bactericidal cumulative fraction of response and ciprofloxacin 61.9% (aggressive scenario) and 56.7% (conservative scenario) respectively. Based on this model, standard doses of beta-lactams were predicted to deliver sufficient pharmacodynamic exposure for outpatients. However, ceftriaxone should be avoided for inpatients and ciprofloxacin empirical prescription should be avoided in both inpatients and outpatients with complicated urinary tract infection.

Spatial exploration of Streptococcus pneumoniae clonal clustering in São Paulo, Brazil

OBJECTIVES To examine the spatial distribution of Streptococcus pneumoniae and its clonal patterns collected between 2002 and 2006 in São Paulo, Brazil. METHODS As part of an observational study in São Paulo city, Brazil, S. pneumoniae isolates routinely cultured from blood, respiratory specimens, or cerebrospinal and other profound fluids were selected. Additionally, only isolates with either penicillin (PEN) intermediate (I) or resistant (R) status on routine antibiogram were included, in order to obtain a higher probability of clonal isolates. A single I/R S. pneumoniae isolate per patient was included and submitted to genotypic determination by pulsed field gel electrophoresis (PFGE). Minimum inhibitory concentrations (MICs) were determined for the isolates by Etest® to PEN and other antimicrobials. Each isolate was geocoded in a digital map. The Kernel function and ratio methods between total isolates vs. clones were used in order to explore possible cluster formations. RESULTS Seventy-eight (78) S. pneumoniae community isolates from two major outpatient centers in São Paulo, Brazil, were selected from the databank according to their penicillin susceptibility profile, i.e. R or I to penicillin assessed by oxacillin disc diffusion. Of these, 69 were submitted to PFGE, 65 to MIC determination, and 48 to spatial analytical procedures. Preliminary spatial analysis method showed two possible cluster formation located in southwest and southeast regions of the city. CONCLUSION Further analyses are required for precisely determining the existence of S. pneumoniae clusters and their related risk factors. Apparently there is a specific transmission pattern of S. pneumoniae clones within certain regions and populations. GIS and spatial methods can be applied to better understand epidemiological patterns and to identify target areas for public health interventions.

Proposta sobre uso de dados de receitas de antimicrobianos retidas: a experiência EUREQA

This study demonstrates that the use of information from medical prescriptions is essential for understanding the dynamics of community bacterial resistance. The resulting analysis can also influence and help establish more adequate public health policies on the control and optimization of antimicrobial use. The article demonstrates the use of a logical model developed by the EUREQA project for acquisition, classification, interpretation, and analysis of data from prescriptions for oral antimicrobial use.

Effect of polymyxin B-containing regimens on renal function for the treatment of carbapenem-resistant Enterobacteriacea mediastinitis

A retrospective cohort study, were evaluated: polymyxin B plus aminoglycosides or polymyxin B plus other antibiotics. Any degree of acute kidney injury occurred in 26 (86.6%) patients. The median time to acute kidney injury was 6.0 (95% CI 3-14) days in the polymyxin-aminoglycoside containing regimen group, against 27.0 (95% CI 6-42) days in the polymyxin with other antimicrobial combinations group (p=0.03). Polymyxin B with aminoglycosides group progressed faster to any degree of renal dysfunction.

O026: Countrywide prevalence study of healthcare-associated infections in brazilian hospitals: preliminary results

frequent (56.0%), among them, Klebsiella spp (19.0%) and Pseudomonas aeruginosa (16%) and were predominant. Among Gram-positives (35.0%), coagulase-negative Staphylococci were more prevalent (16%) than Staphylococcus aureus (9.0%) or Enteroccoccus spp (6%). Yeasts were identified in 9.0% of HAI.

P265: Structure for prevention of healthcare-associated infection in Brazilian Hospitals

Minimal structure is required for an effective prevention of Healthcare-Associated Infection (HAI).