Socioeconomic Determinants of Antibiotic Consumption in the State of São Paulo, Brazil: The Effect of Restricting Over-The-Counter Sales.

BACKGROUND: Improper antibiotic use is one of the main drivers of bacterial resistance to antibiotics, increasing infectious diseases morbidity and mortality and raising costs of healthcare. The level of antibiotic consumption has been shown to vary according to socioeconomic determinants (SED) such as income and access to education. In many Latin American countries, antibiotics could be easily purchased without a medical prescription in private pharmacies before enforcement of restrictions on over-the-counter (OTC) sales in recent years. Brazil issued a law abolishing OTC sales in October 2010. This study seeks to find SED of antibiotic consumption in the Brazilian state of São Paulo (SSP) and to estimate the impact of the 2010 law. METHODS: Data on all oral antibiotic sales having occurred in the private sector in SSP from 2008 to 2012 were pooled into the 645 municipalities of SSP. Linear regression was performed to estimate consumption levels that would have occurred in 2011 and 2012 if no law regulating OTC sales had been issued in 2010. These values were compared to actual observed levels, estimating the effect of this law. Linear regression was performed to find association of antibiotic consumption levels and of a greater effect of the law with municipality level data on SED obtained from a nationwide census. RESULTS: Oral antibiotic consumption in SSP rose from 8.44 defined daily doses per 1,000 inhabitants per day (DID) in 2008 to 9.95 in 2010, and fell to 8.06 DID in 2012. Determinants of a higher consumption were higher human development index, percentage of urban population, density of private health establishments, life expectancy and percentage of females; lower illiteracy levels and lower percentage of population between 5 and 15 years old. A higher percentage of females was associated with a stronger effect of the law. CONCLUSIONS: SSP had similar antibiotic consumption levels as the whole country of Brazil, and they were effectively reduced by the policy

The minimal inhibitory concentration for sulbactam was not associated with the outcome of infections caused by carbapenem-resistant Acinetobacter sp. treated with ampicillin/sulbactam

OBJECTIVE: The objective of this study was to evaluate whether the outcomes of carbapenem-resistant Acinetobacter infections treated with ampicillin/sulbactam were associated with the in vitro susceptibility profiles. METHODS: Twenty-two infections were treated with ampicillin/sulbactam. The median treatment duration was 14 days (range: 3-19 days), and the median daily dose was 9 g (range: 1.5-12 g). The median time between Acinetobacter isolation and treatment was 4 days (range: 0-11 days). RESULTS: The sulbactam minimal inhibitory concentration (MIC) ranged from 2.0 to 32.0 mg/L, and the MIC was not associated with patient outcome, as 4 of 5 (80%) patients with a resistant infection (MIC≥16), 5 of 10 (50%) patients with intermediate isolates (MIC of 8) and only 1 of 7 (14%) patients with susceptible isolates (MIC ≤4) survived hospitalization. CONCLUSION: These findings highlight the need to improve the correlation between in vitro susceptibility tests and clinical outcome

Polymerase chain reaction targeting 16S ribosomal RNA for the diagnosis of bacterial meningitis after neurosurgery

OBJECTIVES: Bacterial and aseptic meningitis after neurosurgery can present similar clinical signs and symptoms. The aims of this study were to develop and test a molecular method to diagnose bacterial meningitis (BM) after neurosurgery. METHODS: A 16S ribosomal RNA gene PCR-based strategy was developed using artificially inoculated cerebrospinal fluid (CSF) followed by sequencing. The method was tested using CSF samples from 43 patients who had undergone neurosurgery and were suspected to suffer from meningitis, and from 8 patients without neurosurgery or meningitis. Patients were classified into five groups, confirmed BM, probable BM, possible BM, unlikely BM, and no meningitis. RESULTS: Among the samples from the 51 patients, 21 samples (41%) were culture-negative and PCR-positive. Of these, 3 (14%) were probable BM, 4 (19%) were possible BM, 13 (62%) were unlikely BM, and 1 (5%) was meningitis negative. Enterobacterales, non-fermenters (Pseudomonas aeruginosa and Acinetobacter baumannii), Staphylococcus haemolyticus, Granulicatella, Variovorax, and Enterococcus cecorum could be identified. In the group of patients with meningitis, a good agreement (3 of 4) was observed with the results of cultures, including the identification of species. CONCLUSION: Molecular methods may complement the diagnosis, guide treatment, and identify non-cultivable microorganisms. We suggest the association of methods for suspected cases of BM after neurosurgery, especially for instances in which the culture is negative

Current Status of Antimicrobial Stewardship Programs in São Paulo Hospitals

OBJECTIVES: Antimicrobial stewardship programs (ASPs) comprise coordinated interventions designed to improve antimicrobial use. Understanding the current structure of ASP hospitals will support interventions for the improvement of these programs. This study aimed to describe the status of ASPs in hospitals in São Paulo, Brazil. METHODS: A cross-sectional survey was conducted on the ASPs of hospitals in the state of São Paulo from March to July 2018. Through interviews by telephone or e-mail, we queried which components of the Infectious Diseases Society of America/Society for Healthcare Epidemiology of America and Centers for Disease Control and Prevention guidelines were implemented. RESULTS: The response rate was 30% (28/93 hospitals), and 26 hospitals (85%) reported having a formal ASP. The most frequently implemented strategies were antimicrobial surgical prophylaxis guidelines (100%), empiric sepsis guidelines (93%), and the presence of ASP team members during bedside rounds (96%). The least commonly implemented strategies included prior authorization for all antimicrobials (11%), pharmacokinetic monitoring, and an adjustment program for patients on IV aminoglycosides (3%). Regarding the metrics of the ASP, the most common indicator was the rate of antimicrobial resistance (77%). Eighteen hospitals evaluated antimicrobial consumption using defined daily dose, and only 29% evaluated the days of therapy; 61% of hospitals reported their results to the hospital administration and 39% to the prescribers. CONCLUSIONS: Most hospitals have a formal and active ASP, but with timely actions. We observed inconsistencies between what program leaders understand as the main objective of ASP and the metrics used to evaluate it. Part of the effort for the next few years should be to improve program evaluation metrics and to provide feedback to physicians and hospital leadership

Using antimicrobial drugs: questions and answers

Para indicar o uso de antimicrobianos é necessário ter à mente várias informações sobre as drogas, tais como espectro de atividade da droga, dados de farmacocinética e farmacodinâmica, como distribuição tecidual, plasmática e excreção, efeitos adversos e é necessário ter várias informações sobre o quadro clínico do paciente e o tipo de infecção e seu agente etiológico, tais como sítio de infecção e sensibilidade antimicrobiana. Não é possível abarcar todos estes aspectos em um artigo e optamos por abordar os princípios gerais do tratamento antimicrobiano por meio de perguntas e respostas. O objetivo é prover os conceitos básicos do uso de antimicrobianos. Apresentamos as principais classes de antimicrobianos e o seu espectro de ação, conceitos como infecção, colonização e contaminação, interpretação de culturas, indicações e duração de tratamento, vias de administração, associação de drogas, critérios de resposta ao tratamento, e profilaxia antimicrobiana.In order to use antimicrobials well it is necessary to have information about the different drugs available, spectrum of activity, pharmacodynamic and pharmacokinetic data such as tissue distribution, excretion and plasma, adverse effects. It is also necessary to have information about the type and site of infection, its causative agent and antimicrobial susceptibility. We could not cover all these aspects in one article and we chose to approach the general principles of antimicrobial treatment using questions and answers. Our goal is to provide the basics for the use of antimicrobials. We present the main classes of antimicrobials and their spectrum, concepts such as infection, colonization and contamination, interpretation of cultures, indications and treatment duration, route of administration, drug combination, criteria to evaluate response to treatment, and antimicrobial prophylaxis

Comparative study of etiological diagnosis of nosocomial pneumonia

Nosocomial pneumonia is a common complication in patients on mechanical ventilation and results in significant mortality. Diagnosis of pneumonia in patients who are intubated and under mechanical ventilation is difficult, even with the aid of clinical, laboratorial, and endoscopic tests. The objective of this study was to compare three methods of tracheal sputum collection in patients with a clinical and radiological diagnosis of pneumonia. Twenty-two patients with a clinical diagnosis of liver disease were enrolled, 18 years of age or older, 13 males and nine females, who had been mechanically ventilated over an intubation period of 5.86 ± 4.62 days. These patients were being treated in intensive care unit (ICU) of the Liver Transplantdepartment. Secretion collection was carried out according to a protocol with three distinct methods: endotracheal aspiration with a closed aspiration system, Bal cath and bronchoalveolar lavage. Of the 22 patients analyzed, 21 (95.4%) showed one or more infectious agent when the closed aspiration system was used. With the Bal cathâ collection, 19 patients (86.3%) had one or more infectious agents; in the collection by bronchoalveolar lavage, 10 patients (45.4%) presented one or more infectious agent. According to the laboratorial analysis, 14 different microorganisms were isolated, the most frequent of which were Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae. We concluded that aspiration with the closed system produced the most effective results in comparison with those of bronchoalveolar lavage and the Bal cathâ, and may be an acceptable method for diagnosing hospital-acquired pneumonia when no fiberoptic technique is available

Comparison of disc diffusion, Etest and broth microdilution for testing susceptibility of carbapenem-resistant P. aeruginosa to polymyxins

Abstract\ud \ud \ud \ud Background\ud \ud Considering the increasing use of polymyxins to treat infections due to multidrug resistant Gram-negative in many countries, it is important to evaluate different susceptibility testing methods to this class of antibiotic.\ud \ud \ud \ud Methods\ud \ud Susceptibility of 109 carbapenem-resistant P. aeruginosa to polymyxins was tested comparing broth microdilution (reference method), disc diffusion, and Etest using the new interpretative breakpoints of Clinical and Laboratory Standards Institute.\ud \ud \ud \ud Results\ud \ud Twenty-nine percent of isolates belonged to endemic clone and thus, these strains were excluded of analysis. Among 78 strains evaluated, only one isolate was resistant to polymyxin B by the reference method (MIC: 8.0 μg/mL). Very major and major error rates of 1.2% and 11.5% were detected comparing polymyxin B disc diffusion with the broth microdilution (reference method). Agreement within 1 twofold dilution between Etest and the broth microdilution were 33% for polymyxin B and 79.5% for colistin. One major error and 48.7% minor errors were found comparing polymyxin B Etest with broth microdilution and only 6.4% minor errors with colistin. The concordance between Etest and the broth microdilution (reference method) was respectively 100% for colistin and 90% for polymyxin B.\ud \ud \ud \ud Conclusion\ud \ud Resistance to polymyxins seems to be rare among hospital carbapenem-resistant P. aeruginosa isolates over a six-year period. Our results showed, using the new CLSI criteria, that the disc diffusion susceptibility does not report major errors (false-resistant results) for colistin. On the other hand, showed a high frequency of minor errors and 1 very major error for polymyxin B. Etest presented better results for colistin than polymyxin B. Until these results are reproduced with a large number of polymyxins-resistant P. aeruginosa isolates, susceptibility to polymyxins should be confirmed by a reference method.Financial support: Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP).Financial support: Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Genetic and virulence characterization of colistin-resistant and colistin-sensitive A. baumannii clinical isolates.

Treatment of infections caused by A. baumannii is becoming a challenge due to the ability to develop multidrug-resistance, virulence, and high mortality. We described the colistin resistance and virulence genes present in sixA. baumannii clinical isolates using WGS, expression by qPCR, and virulence in the Galleria mellonella model. The colistin-resistant isolates were assigned as ST233 and the colistin-susceptible isolates as ST236 and ST407. The colistin-resistant isolates contained mutations within PmrA/PmrB, and the pmrA showed up-regulation in all of them. Only one colistin-resistant isolate indicating virulence in G. mellonella. This particular isolate belonged to a different clone, and it was the only isolate that presented non-synonymous mutations in pmrB. Colistinresistance in A. baumannii isolates seems to be caused by up-regulation of pmrA gene. Only one isolate appeared to be virulent in the G. mellonella model. This finding indicating low virulence in isolates belonging to emerging clones circulating in our hospital

Prospective One Year follow up of HIV infected women screened for cervical cancer using visual inspection with acetic acid, cytology and human papillomavirus testing in Johannesburg, South Africa

BACKGROUND: Cervical cancer is the most common cancer in Sub-Saharan Africa. There are little of HIV-infected women one-year after screening using visual inspection with acetic acid (VIA), HPV or cytology in sub-Saharan Africa. METHODS: HIV-infected women in Johannesburg South Africa were screened one year later by Pap smear, VIA and human papillomavirus (HPV) testing. Women qualified for the 12 month follow-up visit if they had a negative or cervical intra-epithelial neoplasia (CIN) 1 results at the baseline visit. Modified Poisson regression was used to analyse associations between patient baseline characteristics and progression. RESULTS: A total of 688 of 1,202 enrolled at baseline study who were CIN-2+ negative and qualified for a 12 month follow-up visit. Progression to CIN-2+ was higher in women with positive VIA results (12.6%; 24/191) than those VIA-negative (4.4%; 19/432). HPV-positive women at baseline were more likely to progress to CIN-2+ (12.3%; 36/293) than those HPV-negative (2.1%; 7/329). Cytology-positive women at baseline were more likely to progress to CIN-2+ (9.6%; 37/384) than cytology-negative women (2.5%; 6/237). Approximately 10% (10.4%; 39/376) of women with CIN 1 at baseline progressed to CIN 2+. Women who were VIA or HPV positive at baseline were more likely to progress aIRR 1.85, CI 95% (1.46 to 2.36), aIRR 1.41 CI 95% (1.14 to 1.75) respectively. CONCLUSION: Progression to CIN-2+ in HIV-infected women is significant when measured by baseline positive VIA, HPV or Pap and yearly screening by any method should be considered in this population if possible

Prompt atmospheric neutrino fluxes: perturbative QCD models and nuclear effects

We evaluate the prompt atmospheric neutrino flux at high energies using three different frameworks for calculating the heavy quark production cross section in QCD: NLO perturbative QCD, $k_T$ factorization including low-$x$ resummation, and the dipole model including parton saturation. We use QCD parameters, the value for the charm quark mass and the range for the factorization and renormalization scales that provide the best description of the total charm cross section measured at fixed target experiments, at RHIC and at LHC. Using these parameters we calculate differential cross sections for charm and bottom production and compare with the latest data on forward charm meson production from LHCb at $7$ TeV and at $13$ TeV, finding good agreement with the data. In addition, we investigate the role of nuclear shadowing by including nuclear parton distribution functions (PDF) for the target air nucleus using two different nuclear PDF schemes. Depending on the scheme used, we find the reduction of the flux due to nuclear effects varies from $10\%$ to $50 \%$ at the highest energies. Finally, we compare our results with the IceCube limit on the prompt neutrino flux, which is already providing valuable information about some of the QCD models.Comment: 61 pages, 25 figures, 11 table