RESUMO
BACKGROUND: The clinical use of colistin methanesulphonate (CMS) is limited by potential nephrotoxicity. The selection of an efficient and safe CMS dose for individual patients is complicated by the narrow therapeutic window and high interpatient pharmacokinetic variability. In this study, a simple predictive equation for estimating the plasma concentration of formed colistin in patients with multidrug and extremely drug-resistant gram-negative bacterial infections was developed. METHODS: The equation was derived from the largest clinical cohort of patients undergoing therapeutic drug monitoring (TDM) of colistin for over 8 years in a tertiary Spanish hospital. All variables associated with Css,avg were selected in a multiple linear regression model that was validated in a second cohort of 40 patients. Measured Css,avg values were compared with those predicted by our model and a previous published algorithm for critically ill patients. RESULTS: In total, 276 patients were enrolled [the mean age was 67.2 (13.7) years, 203 (73.6%)] were male, and the mean (SD) Css,avg was 1.12 (0.98) mg/L. Age, gender, estimated glomerular filtration rate, CMS dose and frequency, and concomitant drugs were included in the model. In the external validation, the previous algorithm appeared to yield more optimized colistin plasma concentrations when all types of Css,avg values (high and low) were considered, while our equation yielded a more optimized prediction in the subgroup of patients with low colistin plasma concentrations (Css,avg <1.5 mg/L). CONCLUSIONS: The proposed equation may help clinicians to better use CMS among a wide variety of patients, to maximize efficacy and prevent nephrotoxicity. A further prospective PK study is warranted to externally validate this algorithm.
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An increase in invasive group A Streptococcus infection was detected in the northeast of Spain in November 2022. A postpandemic decline in the diversity of circulating emm types involved in invasive group A Streptococcus was observed, along with the emergence of emm49 in this geographic area.
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Proteínas da Membrana Bacteriana Externa , Infecções Estreptocócicas , Humanos , Espanha/epidemiologia , Proteínas da Membrana Bacteriana Externa/genética , Antígenos de Bactérias/genética , Proteínas de Transporte/genética , Streptococcus pyogenes/genética , Infecções Estreptocócicas/epidemiologiaRESUMO
BACKGROUND: The objective of this study was to determine the minimum number of cultures needed to detect Cutibacterium acnes in primary reverse shoulder arthroplasties (RSAs). METHODS: It is a prospective study including 160 primary RSAs. Exclusion criteria included an active infection, an invasive shoulder treatment in the last 6 months before surgery, an Arthro-SCAN or Arthro-MRI in the last 6 months before surgery, previous shoulder surgeries and revision cases. In 90 cases, 11 cultures were obtained. Another 10 cultures were obtained in the other 70 cases (culture 10 was a sterile sponge to detect false positives). To determine the minimum number of cultures needed to detect C acnes, the prevalence of C acnes contamination of the 160 patients included was determined. RESULTS: There were 128 females and 32 males, with a mean age of 74 years. There were 1690 cultures obtained from the 160 primary RSA surgeries, and 132 of them turned out to be positive for C acnes. There were 42 patients with positive cultures. Twenty of them were males and 22 females. When considering the skin and the deep tissue cultures altogether, the prevalence of positive cultures for C acnes was of 26.25%. If only deep tissues cultures were considered, the prevalence of positive cultures for C acnes was of 23.13%. When considering the skin and the deep tissue cultures together, the sensitivity to detect the C acnes is 19% if only 1 culture is obtained, 31% if 2 cultures are obtained, 50% if 3 cultures are obtained, 59.5% if 4 cultures are obtained, 66.7% if 5 cultures are obtained, 73.8% if 6 cultures are obtained, 85.7% if 7 cultures are obtained, and 92.9% if 8 cultures are obtained. When considering only the deep tissue cultures, if only 1 culture is obtained, the sensitivity to detect the C acnes is 24.3%, 40.5% if 2 cultures are obtained, 54.1% if 3 cultures are obtained, 73% if 4 cultures are obtained, 89.2% if 5 cultures are obtained, and 97.3% if 6 or 7 cultures are obtained. DISCUSSION: A minimum number of 8 cultures are needed to detect C acnes in skin. Moreover, a minimum of 6 cultures are needed to detect it in deep tissues when performing an RSA.
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Artroplastia do Ombro , Infecções por Bactérias Gram-Positivas , Articulação do Ombro , Masculino , Feminino , Humanos , Idoso , Estudos Prospectivos , Articulação do Ombro/cirurgia , Articulação do Ombro/microbiologia , Propionibacterium acnes , Artroplastia , Ombro/cirurgia , Infecções por Bactérias Gram-Positivas/diagnóstico , Infecções por Bactérias Gram-Positivas/epidemiologia , Infecções por Bactérias Gram-Positivas/microbiologiaRESUMO
The purpose of this study was to investigate if the C. acnes present at the end of a primary shoulder arthroplasty could be responsible for shoulder arthroplasty infection. Prospective study includes patients undergoing primary shoulder arthroplasty from January 2015 until December 2018. From all the patients included, 5 to 12 tissue samples were obtained and were specifically cultured to detect the presence of C. acnes. DNA was extracted from the C acnes isolated colonies and Whole Genome Sequencing (WGS) analysis was done. A cohort of 156 patients was finally included. In twenty-seven patients, the C. acnes was present at the end of the primary surgery. Two of these patients developed a C. acnes periprosthetic shoulder infection at 6 and 4 months after the primary surgery. WGS of C. acnes isolated colonies showed that all the revision-surgery isolates clustered near to the corresponding primary-surgery isolates compared to the other independent bacterial colonies. (99.89% of similarity). C. acnes present at the end of the primary surgery can be the cause of early or delayed periprosthetic joint infections in shoulder arthroplasty.
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Infecções por Bactérias Gram-Positivas/microbiologia , Complicações Pós-Operatórias/microbiologia , Propionibacterium acnes/isolamento & purificação , Prótese de Ombro/microbiologia , Ombro/microbiologia , Idoso , Idoso de 80 Anos ou mais , Artroplastia/efeitos adversos , Feminino , Genoma Bacteriano , Humanos , Masculino , Pessoa de Meia-Idade , Propionibacterium acnes/genética , Propionibacterium acnes/crescimento & desenvolvimento , Estudos Prospectivos , Ombro/cirurgiaRESUMO
Combination therapy is an attractive therapeutic option for extensively drug-resistant (XDR) Pseudomonas aeruginosa infections. Colistin has been the only treatment available for these infections for many years, but its results are suboptimal. Ceftolozane-tazobactam (C/T) is a newly available therapeutic option that has shown good antipseudomonal activity, even against a number of XDR P. aeruginosa strains. However, data about combinations containing C/T are scarce. The aim of this study was to analyze the activity of C/T and colistin alone and in combination against a collection of XDR P. aeruginosa strains containing 24 representative clinical isolates from a multicentre Spanish study. Twenty-four time-kill experiments performed over 24 h were conducted in duplicate to determine the effects of colistin and C/T alone and combined. An in vitro pharmacodynamic chemostat model then was used to validate this combination against three selected XDR P. aeruginosa ST175 isolates with different susceptibility levels to C/T. Static time-kill assays demonstrated superior synergistic or additive effect for C/T plus colistin against 21 of the 24 isolates studied. In the in vitro dynamic pharmacokinetic/pharmacodynamic (PK/PD) model, the C/T regimen of 2/1 g every 8 h with a steady-state concentration of 2 mg/liter colistin effectively suppressed the bacterial growth at 24 h. Additive or synergistic interactions were observed for C/T plus colistin against XDR P. aeruginosa strains and particularly against C/T-resistant strains. C/T plus colistin may be a useful treatment for XDR P. aeruginosa infections, including those caused by high risk-clones resistant to C/T.
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Antibacterianos/farmacologia , Cefalosporinas/farmacologia , Colistina/farmacologia , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Tazobactam/farmacologia , Antibacterianos/farmacocinética , Cefalosporinas/farmacocinética , Colistina/farmacocinética , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Modelos Biológicos , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/crescimento & desenvolvimento , Tazobactam/farmacocinética , Resistência beta-Lactâmica/efeitos dos fármacosRESUMO
BACKGROUND: There is little information about the efficacy of active alternative drugs to carbapenems except ß-lactam/ß-lactamase inhibitors for the treatment of bloodstream infections (BSIs) due to extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E). The objective of this study was to assess the outcomes of patients with BSI due to ESBL-E who received empiric therapy with such drugs (other active drugs [OADs]) or carbapenems. METHODS: A multinational retrospective cohort study of patients with BSI due to ESBL-E who received empiric treatment with OADs or carbapenems was performed. Cox regression including a propensity score for receiving OADs was performed to analyze 30-day all-cause mortality as main outcome. Clinical failure and length of stay were also analyzed. RESULTS: Overall, 335 patients were included; 249 received empiric carbapenems and 86 OADs. The most frequent OADs were aminoglycosides (43 patients) and fluoroquinolones (20 patients). Empiric therapy with OADs was not associated with mortality (hazard ratio [HR], 0.75; 95% confidence interval [CI], .38-1.48) in the Cox regression analysis. Propensity score-matched pairs, subgroups, and sensitivity analyses did not show different trends; specifically, the adjusted HR for aminoglycosides was 1.05 (95% CI, .51-2.16). OADs were neither associated with 14-day clinical failure (adjusted odds ratio, 0.62; 95% CI, .29-1.36) nor length of hospital stay. CONCLUSIONS: We were unable to show that empiric treatment with OAD was associated with a worse outcome compared with carbapenems. This information allows more options to be considered for empiric therapy, at least for some patients, depending on local susceptibility patterns of ESBL-E.
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Antibacterianos , Bacteriemia , Infecções por Enterobacteriaceae , Enterobacteriaceae , Resistência beta-Lactâmica , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Carbapenêmicos/farmacologia , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/enzimologia , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/microbiologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , beta-LactamasesRESUMO
Background: Bloodstream infections (BSIs) due to ESBL-producing Enterobacteriaceae (ESBL-E) are frequent yet outcome prediction rules for clinical use have not been developed. The objective was to define and validate a predictive risk score for 30 day mortality. Methods: A multinational retrospective cohort study including consecutive episodes of BSI due to ESBL-E was performed; cases were randomly assigned to a derivation cohort (DC) or a validation cohort (VC). The main outcome variable was all-cause 30 day mortality. A predictive score was developed using logistic regression coefficients for the DC, then tested in the VC. Results: The DC and VC included 622 and 328 episodes, respectively. The final multivariate logistic regression model for mortality in the DC included age >50 years (OR = 2.63; 95% CI: 1.18-5.85; 3 points), infection due to Klebsiella spp. (OR = 2.08; 95% CI: 1.21-3.58; 2 points), source other than urinary tract (OR = 3.6; 95% CI: 2.02-6.44; 3 points), fatal underlying disease (OR = 3.91; 95% CI: 2.24-6.80; 4 points), Pitt score >3 (OR = 3.04; 95 CI: 1.69-5.47; 3 points), severe sepsis or septic shock at presentation (OR = 4.8; 95% CI: 2.72-8.46; 4 points) and inappropriate early targeted therapy (OR = 2.47; 95% CI: 1.58-4.63; 2 points). The score showed an area under the receiver operating curve (AUROC) of 0.85 in the DC and 0.82 in the VC. Mortality rates for patients with scores of < 11 and ≥11 were 5.6% and 45.9%, respectively, in the DC, and 5.4% and 34.8% in the VC. Conclusions: We developed and validated an easy-to-collect predictive scoring model for all-cause 30 day mortality useful for identifying patients at high and low risk of mortality.
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Bacteriemia/mortalidade , Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/mortalidade , Enterobacteriaceae/enzimologia , beta-Lactamases/biossíntese , Idoso , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Infecções por Enterobacteriaceae/tratamento farmacológico , Feminino , Humanos , Klebsiella/enzimologia , Klebsiella/isolamento & purificação , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/mortalidade , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Sepse/tratamento farmacológicoRESUMO
The spread of extended-spectrum-ß-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E) is leading to increased carbapenem consumption. Alternatives to carbapenems need to be investigated. We investigated whether ß-lactam/ß-lactamase inhibitor (BLBLI) combinations are as effective as carbapenems in the treatment of bloodstream infections (BSI) due to ESBL-E. A multinational, retrospective cohort study was performed. Patients with monomicrobial BSI due to ESBL-E were studied; specific criteria were applied for inclusion of patients in the empirical-therapy (ET) cohort (ETC; 365 patients), targeted-therapy (TT) cohort (TTC; 601 patients), and global cohort (GC; 627 patients). The main outcome variables were cure/improvement rate at day 14 and all-cause 30-day mortality. Multivariate analysis, propensity scores (PS), and sensitivity analyses were used to control for confounding. The cure/improvement rates with BLBLIs and carbapenems were 80.0% and 78.9% in the ETC and 90.2% and 85.5% in the TTC, respectively. The 30-day mortality rates were 17.6% and 20% in the ETC and 9.8% and 13.9% in the TTC, respectively. The adjusted odds ratio (OR) (95% confidence interval [CI]) values for cure/improvement rate with ET with BLBLIs were 1.37 (0.69 to 2.76); for TT, they were 1.61 (0.58 to 4.86). Regarding 30-day mortality, the adjusted OR (95% CI) values were 0.55 (0.25 to 1.18) for ET and 0.59 (0.19 to 1.71) for TT. The results were consistent in all subgroups studied, in a stratified analysis according to quartiles of PS, in PS-matched cases, and in the GC. BLBLIs, if active in vitro, appear to be as effective as carbapenems for ET and TT of BSI due to ESLB-E regardless of the source and specific species. These data may help to avoid the overuse of carbapenems. (This study has been registered at ClinicalTrials.gov under registration no. NCT01764490.).
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Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Enterobacteriaceae/enzimologia , Enterobacteriaceae/patogenicidade , Inibidores de beta-Lactamases/uso terapêutico , beta-Lactamases/metabolismo , beta-Lactamas/metabolismo , Idoso , Bacteriemia/microbiologia , Bacteriemia/mortalidade , Carbapenêmicos/uso terapêutico , Enterobacteriaceae/efeitos dos fármacos , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Estudos RetrospectivosRESUMO
OBJECTIVES: Data about the efficacy of ertapenem for the treatment of bloodstream infections (BSI) due to ESBL-producing Enterobacteriaceae (ESBL-E) are limited. We compared the clinical efficacy of ertapenem and other carbapenems in monomicrobial BSI due to ESBL-E. METHODS: A multinational retrospective cohort study (INCREMENT project) was performed (ClinicalTrials.gov identifier: NCT01764490). Patients given monotherapy with ertapenem or other carbapenems were compared. Empirical and targeted therapies were analysed. Propensity scores were used to control for confounding; sensitivity analyses were performed in subgroups. The outcome variables were cure/improvement rate at day 14 and all-cause 30 day mortality. RESULTS: The empirical therapy cohort (ETC) and the targeted therapy cohort (TTC) included 195 and 509 patients, respectively. Cure/improvement rates were 90.6% with ertapenem and 75.5% with other carbapenems (Pâ=â0.06) in the ETC and 89.8% and 82.6% (Pâ=â0.02) in the TTC, respectively; 30 day mortality rates were 3.1% and 23.3% (Pâ=â0.01) in the ETC and 9.3% and 17.1% (Pâ=â0.01) in the TTC, respectively. Adjusted ORs (95% CI) for cure/improvement with empirical and targeted ertapenem were 1.87 (0.24-20.08; Pâ=â0.58) and 1.04 (0.44-2.50; Pâ=â0.92), respectively. For the propensity-matched cohorts it was 1.18 (0.43-3.29; Pâ=â0.74). Regarding 30 day mortality, the adjusted HR (95% CI) for targeted ertapenem was 0.93 (0.43-2.03; Pâ=â0.86) and for the propensity-matched cohorts it was 1.05 (0.46-2.44; Pâ=â0.90). Sensitivity analyses were consistent except for patients with severe sepsis/septic shock, which showed a non-significant trend favouring other carbapenems. CONCLUSIONS: Ertapenem appears as effective as other carbapenems for empirical and targeted therapy of BSI due to ESBL-E, but further studies are needed for patients with severe sepsis/septic shock.
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Antibacterianos/uso terapêutico , Carbapenêmicos/uso terapêutico , Infecções por Enterobacteriaceae/tratamento farmacológico , Enterobacteriaceae/enzimologia , Sepse/tratamento farmacológico , beta-Lactamases/metabolismo , beta-Lactamas/uso terapêutico , Idoso , Enterobacteriaceae/isolamento & purificação , Infecções por Enterobacteriaceae/microbiologia , Ertapenem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sepse/microbiologia , Análise de Sobrevida , Resultado do TratamentoRESUMO
Molecular techniques have represented a major step forward in the diagnosis of viral respiratory infections. They are considered highly sensitive and specific compared to conventional techniques. In this study two nucleic acid amplification tests (NAATs) were compared to conventional methods (immunofluorescence and viral culture). The aim of this work was to discuss the clinical interpretation of the results obtained by NAATs on the basis of the two-decade experience of our group and the literature. Eighty nasopharyngeal aspirates were collected from children under six years attended for acute respiratory illness at the pediatric emergency room of a third level Hospital. Both NAATs tested (Seeplex(®) and Clart(®)) showed an overall higher performance regarding sensitivity (76% and 90%, respectively). Compared to Seeplex(®), the Clart(®) system tripled the number of multiple detections (8 by Seeplex(®) vs. 25 by Clart(®)). In some specimens both NAATs detected different viruses. Given these discrepancies and the fact that detection of viral nucleic acids is not necessarily related to the current clinical syndrome, the interpretation of molecular results may not always be so straightforward. The pros and cons of NAATs should always be taken into account when giving a result.
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Técnicas de Diagnóstico Molecular/métodos , Reação em Cadeia da Polimerase Multiplex/métodos , Infecções Respiratórias/diagnóstico , Vírus/classificação , Vírus/isolamento & purificação , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Nasofaringe/virologia , Infecções Respiratórias/virologia , Sensibilidade e Especificidade , Vírus/genéticaRESUMO
Colistin resistance was detected in 53 of 10,011 Escherichia coli (0.5%) by prospective phenotypic testing of consecutive clinical isolates in a single hospital in Barcelona, Spain (2012-15). The mcr-1 gene was retrospectively identified by PCR and sequencing in 15 of 50 available isolates. Each isolate had a unique PFGE pattern except for two. This clonal diversity supports the hypothesis of horizontal dissemination of the mcr-1 gene in the local study population.
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Antibacterianos/farmacologia , Colistina/farmacologia , Farmacorresistência Bacteriana/genética , Infecções por Escherichia coli/tratamento farmacológico , Escherichia coli/efeitos dos fármacos , Escherichia coli/isolamento & purificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Eletroforese em Gel de Campo Pulsado , Escherichia coli/genética , Infecções por Escherichia coli/epidemiologia , Genótipo , Humanos , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Fenótipo , Reação em Cadeia da Polimerase , Prevalência , Estudos Prospectivos , Espanha/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Combination therapy is an attractive therapeutic option for extensively drug-resistant (XDR) Pseudomonas aeruginosa infections. Existing data support the combination of aztreonam and ceftazidime/avibactam (CZA) against class serine-ß-lactamase (SBL)- and metallo-ß-lactamase (MBL) - producing Enterobacterales. However, data about that combination against SBL- and MBL-producing P. aeruginosa are scarce. The objective of the study was to assess the in vitro activity of CZA and aztreonam alone and in combination against SBL- and MBL-producing XDR P. aeruginosa isolates. METHODS: The combination was analyzed by means of the hollow-fiber infection model in three selected carbapenemase-producing P. aeruginosa isolates that were representative of the three most common XDRP. aeruginosa high-risk clones (ST175, ST111, ST235) responsible for global nosocomial infection outbreaks. RESULTS: The three isolates were nonsusceptible to CZA and nonsusceptible to aztreonam. In the dynamic hollow-fiber infection model, the combination of CZA plus aztreonam exerts a bactericidal effect on the isolates, regardless of their resistance mechanism and demonstrates synergistic interactions against three isolates, achieving a bacterial reduction of 5.07 log10 CFU/ml, 5.2 log10 CFU/ml and 4 log10 CFU/ml, respectively. CONCLUSION: The combination of CZA and aztreonam significantly enhanced the in vitro efficacy against XDR P. aeruginosa isolates compared to each monotherapy. This improvement suggests that the combination could serve as a feasible treatment alternative for infections caused by carbapenemase-producing XDR P. aeruginosa, especially in scenarios where no other treatment options are available.
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Cell culture is still the gold standard for the diagnosis of human enteroviruses (HEVs) although molecular techniques are required for detection of some serotypes. Due to the diversity of HEVs, a single cell line is not susceptible to all serotypes, and several lines are required to optimize the isolation of HEVs. In this study, the results of HEV isolation during the last 25 years are reported. A total of 1,192 HEVs were isolated and isolation rates varied depending on the cell line used. MRC5 cells yielded the best results (70.7%), followed by A549 cells (52.6%), RD cells (37.5%), and HEp-2 cells (29.7%). A total of 521 HEVs were characterized, and HEV-B was the most frequent species (81%). Polioviruses (PV) and HEV-A were isolated less frequently (17% and 1%, respectively). None of the cell lines detected all the enteroviruses. MRC5 cells were the most susceptible for isolation of echoviruses (85.7%) and PVs (85.4%), whereas HEp2 was the most susceptible for Coxsackieviruses B (82.6%). Some serotypes were isolated in one cell line only. 40.5% of echoviruses were isolated in MRC5 cells whereas 42.3% and 23.9% of Coxsackieviruses B were isolated in RD cells and HEp2 cells, respectively. Although A549 cells did not achieve the best performance for any enterovirus serotypes, they isolated 52.6% of the total HEVs. In view of these results, MRC5 cells, A549 cells, and RD cells should be combined to optimize isolation of HEVs.
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Técnicas de Laboratório Clínico/métodos , Infecções por Enterovirus/diagnóstico , Infecções por Enterovirus/virologia , Enterovirus/crescimento & desenvolvimento , Enterovirus/isolamento & purificação , Virologia/métodos , Animais , Técnicas de Cultura de Células/métodos , Linhagem Celular , HumanosRESUMO
INTRODUCTION: Enterococcus faecium is a commensal microorganism that can cause infections such as bacteremia. Incidence of ampicillin-resistant and vancomycin-susceptible E. faecium (EfARSV) bacteremia is on the rise, and the mortality rate is high. Despite much data, the most appropriate treatment remains a question. AREAS COVERED: This article mostly reviews the relevant aspects of EfARSV bacteremia: microbiology, gastrointestinal tract colonization and invasion, antibiotic resistance, epidemiology, risk factors, mortality, and treatment, including pharmacologic components of employed agents and related clinical evidence. A literature search was conducted on PubMed on 31 July 2022, which was updated on 15 November 2022. EXPERT OPINION: EfARSV bacteremia presents high mortality. However, it is uncertain whether mortality is attributable to or a marker of severity/comorbidities. Considering its antibiotic resistance pattern, EfARSV is considered a difficult-to-treat microorganism. Glycopeptides have been used to treat EfARSV, with linezolid and daptomycin serving as potential alternative agents. Yet, the use of daptomycin is controversial due to a higher risk of treatment failures. Clinical evidence on this issue is scarce, unfortunately, and subject to many limitations. Despite increased incidence and mortality, EfARSV bacteremia presents multiple aspects to be addressed in well-conducted studies.
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Bacteriemia , Daptomicina , Enterococcus faecium , Infecções por Bactérias Gram-Positivas , Humanos , Antibacterianos/efeitos adversos , Vancomicina/farmacologia , Vancomicina/uso terapêutico , Daptomicina/efeitos adversos , Resultado do Tratamento , Bacteriemia/tratamento farmacológico , Bacteriemia/epidemiologia , Ampicilina/farmacologia , Ampicilina/uso terapêutico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/epidemiologiaRESUMO
Helicobacter pylori is one of the most widespread infections, and it is reaching alarming resistance levels worldwide. The recommended first-line empirical treatment differs according to the local rate of clarithromycin resistance. Macrolide resistance is mainly associated with three point mutations in the 23S rRNA gene. The aim of this study was to describe the antibiotic susceptibility of H. pylori in our healthcare area and the main mechanisms involved in clarithromycin resistance. Gastric biopsies (n = 641) were collected and cultured in a one-year prospective study. Antibiotic susceptibility testing was performed by gradient diffusion. A multiplex real-time PCR test (AllplexTMH.pylori & ClariR Assay, Seegene) was used to detect the most frequent mutations associated with clarithromycin resistance. Overall, 141 isolates were available for antibiotic susceptibility testing. The highest resistance rates were detected in metronidazole and levofloxacin. The rate of clarithromycin resistance was 12.1%, and the associated mutations were A2143G and A2142G. More than half of the clarithromycin-resistant isolates presented high MIC values (>256 mg/L). Tetracycline resistance was not detected, suggesting that therapies that contain tetracycline could be a suitable option. The low clarithromycin resistance rate coupled with the high rates of metronidazole resistance may support the recovery of the classical triple therapy in our healthcare area.
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IMPORTANCE: In some cases, colistin is the only treatment option for infections caused by the very drug-resistant Pseudomonas aeruginosa. However, in the past decade, there have been questions concerning its pharmacokinetics and concentration at the site of infection. In this scenario, its use in a difficult-to-treat infection like pneumonia is currently debatable. This is a clinical pharmacokinetic study of colistin in patients with multidrug-resistant P. aeruginosa pneumonia. Our findings demonstrate that colistin exposure is associated with worse clinical outcomes rather than better clinical outcomes, implying that other therapeutic options should be explored in this clinical setting.
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Pneumonia , Infecções por Pseudomonas , Humanos , Colistina/uso terapêutico , Antibacterianos/farmacologia , Pseudomonas aeruginosa , Farmacorresistência Bacteriana Múltipla , Pneumonia/tratamento farmacológico , Infecções por Pseudomonas/tratamento farmacológico , Testes de Sensibilidade MicrobianaRESUMO
This study correlates in vivo findings in a patient with an extensively drug-resistant (XDR) P. aeruginosa infection who developed resistance to ceftazidime-avibactam (CAZ-AVI) with in vitro results of a 7-day hollow-fiber infection model (HFIM) testing the same bacterial strain. The patient was critically ill with ventilator-associated pneumonia caused by XDR P. aeruginosa ST175 with CAZ-AVI MIC of 6 mg/L and was treated with CAZ-AVI in continuous infusion at doses adjusted for renal function. Plasma concentrations of CAZ-AVI were analyzed on days 3, 7, and 10. In the HIFM, the efficacy of different steady-state concentrations (Css) of CAZ-AVI (12, 18, 30 and 48 mg/L) was evaluated. In both models, a correlation was observed between the decreasing plasma levels of CAZ-AVI and the emergence of resistance. In the HIFM, a Css of 30 and 48 mg/L (corresponding to 5× and 8× MIC) had a bactericidal effect without selecting resistant mutants, whereas a Css of 12 and 18 mg/L (corresponding to 2× and 3× MIC) failed to prevent the emergence of resistance. CAZ/AVI resistance development was caused by the selection of a single ampC mutation in both patient and HFIM. Until further data are available, strategies to achieve plasma CAZ-AVI levels at least 4× MIC could be of interest, particularly in severe and high-inoculum infections caused by XDR P. aeruginosa with high CAZ-AVI MICs.
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A non-systematic review of the published scientific evidence has been carried out on the duration of empirical antibiotic treatment in surgical intra-abdominal infections (IIA) with effective focus control. Given the progressive increase in antibiotic resistance, it is urgent to have strategies to reduce the pressure on the microbiota. The American guidelines made by Mazuski et al. of 20171, as the central axis in the recommendations of the duration of empirical antibiotic treatment in intra-abdominal infections with control of the focus and a bibliographic search of all the articles that contained the keywords in Pubmed and Google Scholar is added. 21 articles referring to the duration of empirical antibiotic treatment in intra-abdominal infection with control of the focus are collected. With the American guidelines and these articles, a proposal is prepared for the duration of empirical antibiotic treatment in patients without risk factors between 24 and 72 h. And in those who present risk factors, it should be individualized with active monitoring every 24 h of fever, paralytic ileus and leukocytosis (FIL), before an early detection of complications or the need for changes in antibiotic treatment. Short treatments are just as effective as those of longer durations and are associated with fewer adverse effects, therefore, daily adjusting and reassessing the duration of empirical antibiotic treatment is essential for better practice.
Assuntos
Infecções Intra-Abdominais , Antibacterianos/uso terapêutico , Humanos , Infecções Intra-Abdominais/tratamento farmacológico , Estados UnidosRESUMO
The aim of this study was to compare the efficacy of intermittent (1-h), extended (4-h), and continuous ceftolozane-tazobactam (C/T) infusion against three extensively drug-resistant (XDR) sequence type (ST) 175 P. aeruginosa isolates with different susceptibilities to C/T (MIC = 2 to 16 mg/L) in a 7-day hollow-fiber infection model (HFIM). C/T in continuous infusion achieved the largest reduction in total number of bacterial colonies in the overall treatment arms for both C/T-susceptible and -resistant isolates. It was also the only regimen with bactericidal activity against all three isolates. These data suggest that continuous C/T infusion should be considered a potential treatment for infections caused by XDR P. aeruginosa isolates, including nonsusceptible ones. Proper use of C/T dosing regimens may lead to better clinical management of XDR P. aeruginosa infections. IMPORTANCE Ceftolozane-tazobactam (C/T) is an antipseudomonal antibiotic with a high clinical impact in treating infection caused by extensively drug-resistant (XDR) Pseudomonas aeruginosa isolates, but resistance is emerging. Given its time-dependent behavior, C/T continuous infusion can improve exposure and therefore the pharmacokinetic/pharmacodynamic target attainment. We compared the efficacy of intermittent, extended, and continuous C/T infusion against three XDR ST175 P. aeruginosa isolates with different C/T MICs by means of an in vitro dynamic hollow-fiber model. We demonstrated that C/T in continuous infusion achieved the largest reduction in bacterial density in the overall treatment arms for both susceptible and resistant isolates. It was also the only regimen with bactericidal activity against all three isolates. Through this study, we want to demonstrate that developing individually tailored antimicrobial treatments is becoming essential. Our results support the role of C/T level monitoring and of dose adjustments for better clinical management and outcomes.