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1.
Medicine (Baltimore) ; 99(10): e19466, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32150105

RESUMO

Multidrug-resistant bacterial (MDRB) infections have been difficult to treat clinically. Tigecycline (TIG) has several advantages, especially in the treatment of severe infections. Many clinicians have considered increasing the TIG dose to improve the efficacy of this molecule. The safety and efficacy of high-dose TIG in elderly patients with MDRB infections were investigated in this study.We conducted a retrospective analysis of the elderly patients with MDRB infections who were treated at the First Affiliated Hospital. A total of 106 patients received a conventional dose (CD-TIG group: 50 mg every 12 hours) of TIG and 51 received a high dose (HD-TIG group: 100 mg every 12 hours). The data from all patients were collected for examining the clinical features and performing the microbiological analysis. The safety profile and efficacy of the HD regimen were investigated.The clinical efficacy and microbiological eradication in the patients with MDRB infection were higher in the HD-TIG group than the CD-TIG group. The independent predictors of clinical cure were the use of TIG at HD (odd ratio [OR], 5.129; 95% confidence interval [CI] [1.890, 13.921]; P = .001) and microbiological eradication (OR, 3.049; 95% CI, [1.251, 7.430]; P = .014). In the ventilator-associated pneumonia (VAP) and bloodstream infection (BSI) subgroups, the sole independent predictor of clinical cure was the HD of TIG, and no significant adverse events were observed. The occurrence of multidrug-resistant Acinetobacter baumannii infection and an MIC value of 1 to 2 g/mL for TIG were independently associated with clinical failure in the VAP subgroup.HDs of TIG was found to associate with better clinical efficacy and microbiological eradication than its CDs in the elderly patients with MDRB infections. In the VAP and BSIs subgroups, administration of HDs of TIG was associated with better outcomes.


Assuntos
Infecções por Acinetobacter/tratamento farmacológico , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Tigeciclina/uso terapêutico , APACHE , Acinetobacter baumannii/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Tigeciclina/administração & dosagem , Tigeciclina/farmacologia , Resultado do Tratamento
2.
Int J Antimicrob Agents ; 55(3): 105862, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31837449

RESUMO

This study aimed to investigate the mechanisms of colistin resistance in 64 Acinetobacter baumannii isolates obtained from patients with ventilator-associated pneumonia hospitalised in Greece, Italy and Spain. In total, 31 A. baumannii isolates were colistin-resistant. Several novel amino acid substitutions in PmrCAB were found in 27 colistin-resistant A. baumannii. Most substitutions were detected in PmrB, indicating the importance of the histidine kinase for colistin resistance. In two colistin-resistant isolates, 93 amino acid changes were observed in PmrCAB compared with A. baumannii ACICU, and homologous recombination across different clonal lineages was suggested. Analysis of gene expression revealed increased pmrC expression in isolates harbouring pmrCAB mutations. Complementation of A. baumannii ATCC 19606 and ATCC 17978 with a pmrAB variant revealed increased pmrC expression but unchanged colistin MICs, indicating additional unknown factors associated with colistin resistance. Moreover, a combination of PmrB and PmrC alterations was associated with very high colistin MICs, suggesting accumulation of mutations as the mechanism for high-level resistance. The pmrC homologue eptA was detected in 29 colistin-susceptible and 26 colistin-resistant isolates. ISAba1 was found upstream of eptA in eight colistin-susceptible and one colistin-resistant isolate and eptA was disrupted by ISAba125 in two colistin-resistant isolates. Whilst in most isolates an association of eptA with colistin resistance was excluded, in one isolate an amino acid substitution in EptA (R127L) combined with a point mutation in ISAba1 upstream of eptA contributed to elevated colistin MICs. This study helps to gain an insight into the diversity and complexity of colistin resistance in A. baumannii.


Assuntos
Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/genética , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Colistina/farmacologia , Pneumonia Associada à Ventilação Mecânica/microbiologia , Infecções por Acinetobacter/tratamento farmacológico , Acinetobacter baumannii/efeitos dos fármacos , Substituição de Aminoácidos , Farmacorresistência Bacteriana/genética , Grécia , Humanos , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico
3.
J Immunoassay Immunochem ; 41(1): 97-105, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31777299

RESUMO

Management of ventilator-associated pneumonia (VAP) is a puzzling issue for infectious disease specialist. The present clinical trial study was aimed to comparing the effects of injectable colistin plus nebulized colistin and injectable colistin plus nebulized tobramycin on management of patients with VAP due to multidrug-resistant Acinetobacter. VAP patients were randomly divided into two groups (n = 30/each): Group 1 - patients that received intravenous (IV) meropenem, injectable colistin plus nebulized colistin, as a routine treatment, and Group 2 - patients that received IV meropenem, injectable colistin plus nebulized tobramycin. A total of 14 days of therapeutic intervention are required for every case. Follow-up for subjects was performed at five time-points: days 1, 3, 5, 7, and 14 after intervention. Also, a mean of creatinine levels of patients was determined in five times. In the present study, the clinical pulmonary infection score (CPIS) was determined on the basis of points assigned for various clinically manifestations of VAP. Based on our statistical analysis, there was no significant difference between CPIS and creatinine level in both Groups 1 and 2 (p > .05). CPIS and other clinical investigation appeared effectiveness of the treatment with injected colistin plus nebulized tobramycin; on the other hand, the results of present clinical trial showed that aforementioned therapeutic approach can be used as an alternative treatment for the management of infection in VAP patients.


Assuntos
Acinetobacter/efeitos dos fármacos , Antibacterianos/farmacologia , Colistina/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Pneumonia Associada à Ventilação Mecânica/microbiologia , Tobramicina/farmacologia , Antibacterianos/administração & dosagem , Antibacterianos/química , Colistina/administração & dosagem , Colistina/química , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Tobramicina/administração & dosagem , Tobramicina/química
4.
Lancet Infect Dis ; 20(3): 330-340, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31866328

RESUMO

BACKGROUND: Treatment of ventilated pneumonia is often unsuccessful, even when patients are treated according to established guidelines. Therefore, we aimed to investigate the efficacy of the combination drug device Amikacin Inhale as an adjunctive therapy to intravenous standard-of-care antibiotics for pneumonia caused by Gram-negative pathogens in intubated and mechanically ventilated patients. METHODS: INHALE was a prospective, double-blind, randomised, placebo-controlled, phase 3 study comprising two trials (INHALE 1 and INHALE 2) done in 153 hospital intensive-care units in 25 countries. Eligible patients were aged 18 years or older; had pneumonia that had been diagnosed by chest radiography and that was documented as being caused by or showing two risk factors for a Gram-negative, multidrug-resistant pathogen; were intubated and mechanically ventilated; had impaired oxygenation within 48 h before screening; and had a modified Clinical Pulmonary Infection Score of at least 6. Patients were stratified by region and disease severity (according to their Acute Physiology and Chronic Health Evaluation [APACHE] II score) and randomly assigned (1:1) via an interactive voice-recognition system to receive 400 mg amikacin (Amikacin Inhale) or saline placebo, both of which were aerosolised, administered every 12 h for 10 days via the same synchronised inhalation system, and given alongside standard-of-care intravenous antibiotics. All patients and all staff involved in administering devices and monitoring outcomes were masked to treatment assignment. The primary endpoint, survival at days 28-32, was analysed in all patients who received at least one dose of study drug, were infected with a Gram-negative pathogen, and had an APACHE II score of at least 10 at diagnosis. Safety analyses were done in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, numbers NCT01799993 and NCT00805168. FINDINGS: Between April 13, 2013, and April 7, 2017, 807 patients were assessed for eligibility and 725 were randomly assigned to Amikacin Inhale (362 patients) or aerosolised placebo (363 patients). 712 patients received at least one dose of study drug (354 in the Amikacin Inhale group and 358 in the placebo group), although one patient assigned to Amikacin Inhale received placebo in error and was included in the placebo group for safety analyses. 508 patients (255 in the Amikacin Inhale group and 253 in the placebo group) were assessed for the primary endpoint. We found no between-group difference in survival: 191 (75%) patients in the Amikacin Inhale group versus 196 (77%) patients in the placebo group survived until days 28-32 (odds ratio 0·841, 95% CI 0·554-1·277; p=0·43). Similar proportions of patients in the two treatment groups had a treatment-emergent adverse event (295 [84%] of 353 patients in the Amikacin Inhale group vs 303 [84%] of 359 patients in the placebo group) or a serious treatment-emergent adverse event (101 [29%] patients vs 97 [27%] patients). INTERPRETATION: Our findings do not support use of inhaled amikacin adjunctive to standard-of-care intravenous therapy in mechanically ventilated patients with Gram-negative pneumonia. FUNDING: Bayer AG.


Assuntos
Administração por Inalação , Amicacina/administração & dosagem , Antibacterianos/administração & dosagem , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Administração Intravenosa , Adulto , Idoso , Antibacterianos/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Hospitais , Humanos , Masculino , Pessoa de Meia-Idade , Placebos/administração & dosagem , Estudos Prospectivos , Padrão de Cuidado , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
5.
Crit Care ; 23(1): 383, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31779711

RESUMO

BACKGROUND: Colistin is recommended in the empirical treatment of ventilator-associated pneumonia (VAP) with a high prevalence of carbapenem-resistant gram-negative bacilli (CR-GNB). However, the efficacy and safety of colistin are not well defined. METHODS: A multicenter prospective randomized trial conducted in 32 European centers compared the efficacy and safety of colistin (4.5 million unit loading dose followed by a maintenance dose of 3 million units every 8 h) versus meropenem (2 g every 8 h), both in combination with levofloxacin (500 mg every 12 h) for 7-14 days in patients with late VAP. Between May 2012 and October 2015, 232 patients were randomly assigned to the 2 treatment groups. The primary endpoint was mortality at 28 days after randomization in the microbiologically modified intention-to-treat (mMITT) population. Secondary outcomes included clinical and microbiological cure, renal function at the end of the treatment, and serious adverse events. The study was interrupted after the interim analysis due to excessive nephrotoxicity in the colistin group; therefore, the sample size was not achieved. RESULTS: A total of 157 (67.7%) patients were included in the mMITT population, 36 of whom (22.9%) had VAP caused by CR-GNB. In the mMITT population, no significant difference in mortality between the colistin group (19/82, 23.2%) and the meropenem group (19/75, 25.3%) was observed, with a risk difference of - 2.16 (- 15.59 to 11.26, p = 0.377); the noninferiority of colistin was not demonstrated due to early termination and limited number of patients infected by carbapenem-resistant pathogens. Colistin plus levofloxacin increased the incidence of renal failure (40/120, 33.3%, versus 21/112, 18.8%; p = 0.012) and renal replacement therapy (11/120, 9.1%, versus 2/112, 1.8%; p = 0.015). CONCLUSIONS: This study did not demonstrate the noninferiority of colistin compared with meropenem, both combined with levofloxacin, in terms of efficacy in the empirical treatment of late VAP but demonstrated the greater nephrotoxicity of colistin. These findings do not support the empirical use of colistin for the treatment of late VAP due to early termination. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01292031. Registered 9 February 2011.


Assuntos
Colistina/normas , Meropeném/normas , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Idoso , Antibacterianos/efeitos adversos , Antibacterianos/normas , Antibacterianos/uso terapêutico , Colistina/efeitos adversos , Colistina/uso terapêutico , Estudos de Equivalência como Asunto , Feminino , Humanos , Masculino , Meropeném/efeitos adversos , Meropeném/uso terapêutico , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
6.
Crit Care ; 23(1): 379, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31775840

RESUMO

BACKGROUND: Augmented renal clearance (ARC) is recognized as a leading cause of ß-lactam subexposure when conventional dosing regimens are used. The main objective was to compare the clinical outcome of ARC patients treated by conventional or increased ß-lactam dosing regimens for a first episode of hospital or ventilator-acquired pneumonia (HAP-VAP). METHODS: In this single-center, retrospective study, every ARC patient treated by ß-lactam for a first episode of HAP-VAP was included during two 15-month periods, before (Control period) and after (Treatment period) the modification of a local antibiotic therapy protocol. ARC was defined by a 24-h measured creatinine clearance ≥ 150 ml/min. The primary endpoint was defined as a therapeutic failure of the antimicrobial therapy or a HAP-VAP relapse within 28 days. Inverse probability of treatment weight (IPTW) was derived from a propensity score model. Cox proportional hazard models were used to evaluate the association between treatment period and clinical outcome. RESULTS: During the study period, 177 patients were included (control period, N = 88; treatment period, N = 89). Therapeutic failure or HAP-VAP relapse was significantly lower in the treatment period (10 vs. 23%, p = 0.019). The IPTW-adjusted hazard ratio of poor clinical outcome in the treatment period was 0.35 (95% CI 0.15-0.81), p = 0.014. No antibiotic side effect was reported during the treatment period. CONCLUSIONS: Higher than licensed dosing regimens of ß-lactams may be safe and effective in reducing the rate of therapeutic failure and HAP-VAP recurrence in critically ill augmented renal clearance (ARC) patients.


Assuntos
Pneumonia/tratamento farmacológico , Resultado do Tratamento , beta-Lactamas/administração & dosagem , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Estado Terminal/terapia , Relação Dose-Resposta a Droga , Feminino , Pneumonia Associada a Assistência à Saúde/tratamento farmacológico , Pneumonia Associada a Assistência à Saúde/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia/epidemiologia , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Pneumonia Associada à Ventilação Mecânica/epidemiologia , Estudos Retrospectivos , beta-Lactamas/uso terapêutico
8.
Int J Infect Dis ; 89: 179-184, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31580939

RESUMO

BACKGROUND: Limited data on healthcare-associated infections (HAIs) are available from the developing world, thus a point prevalence survey was conducted to determine the prevalence of HAIs and antimicrobial use in Guangdong Province, China. METHODS: A standardized methodology for point prevalence surveys on HAIs and antimicrobial use has been developed by the Chinese Nosocomial Infection Control and Quality Improvement Center. The prevalence of HAIs, antimicrobial use, and baseline hospital-level variables were collected in 189 hospitals from June 2017 to May 2018. RESULTS: Of 5 868 147 patients, 72 976 had one or more HAIs (1.24%), with 82 700 distinct HAIs. The prevalence rates of device-associated infections, including ventilator-associated pneumonia, catheter-associated urinary tract infection, and central line-associated bloodstream infection were 7.92, 2.06, and 0.63 per 1000 catheter-days, respectively. A total of 10 591 (0.18%) HAIs caused by multidrug-resistant organisms were identified. Carbapenem non-susceptibility rates were highest in Acinetobacter species (53.86%) and Pseudomonas aeruginosa (21.60%). Forty-six percent (2 712 258/5 868 147) of inpatients were receiving at least one antimicrobial during this survey. CONCLUSIONS: This survey indicated the relatively lower prevalence of HAIs but higher antimicrobial using in Guangdong Province compared with other mid to low-income and high-income countries. Further studies are warranted to elucidate which HAI-related indicators are the best measures of HAI performance and thus allow improvements leading to better patient outcomes.


Assuntos
Antibacterianos/uso terapêutico , Infecção Hospitalar/tratamento farmacológico , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , China , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Estudos Transversais , Hospitais/estatística & dados numéricos , Humanos , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Pneumonia Associada à Ventilação Mecânica/epidemiologia , Pneumonia Associada à Ventilação Mecânica/microbiologia , Prevalência , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/epidemiologia , Infecções Urinárias/microbiologia
9.
Rev. esp. quimioter ; 32(supl.3): 3-10, sept. 2019. ilus, tab, graf
Artigo em Inglês | IBECS | ID: ibc-188972

RESUMO

Ceftobiprole, a novel last generation parenteral cephalosporin, has an extended spectrum of activity, notably against methicillin-resistant Staphylococcus aureus (MRSA), ampicillin-susceptible enterococci, penicillin-resistant pneumococci, Enterobacterales and susceptible Pseudomonas aeruginosa. It exerts an inhibitory action on essential peptidoglycan transpeptidases, interfering with cell wall synthesis. The inhibitory action of ceftobiprole through binding to abnormal PBPs like PBP2a in methicillin-resistant staphylococci and PBP2b and PBP2x in the case of β-lactam-resistant pneumococci, ultimately leads to rapid bacterial cell death. In the case of Enterobacterales, ceftobiprole retains activity against narrow spectrum β-lactamases but is hydrolysed by their extended-spectrum counterparts, overexpressed Amp C, and carbapenemases. It is also affected by certain efflux pumps from P. aeruginosa. For anaerobic bacteria, ceftobiprole is active against Gram-positive Clostridioides difficile and Peptococcus spp. and Gram-negative Fusobacterium nucleatum but not against Bacteroides group or other anaerobic Gram-negatives. In in vitro studies, a low propensity to select for resistant subpopulations has been demonstrated. Currently, ceftobiprole is approved for the treatment of community-acquired pneumonia and hospital-acquired pneumonia with the exception of ventilator-associated pneumonia. Ceftobiprole's place in therapy appears to lie mainly in its combined activity against Gram-positive organisms, such as S. aureus and S. pneumoniae alongside that against Gram-negative organisms such as P. aeruginosa


No disponible


Assuntos
Humanos , Antibacterianos/farmacologia , Cefalosporinas/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/metabolismo , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Resistência às Penicilinas , Proteínas de Ligação às Penicilinas/antagonistas & inibidores , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/metabolismo , Streptococcus pneumoniae/efeitos dos fármacos , Inibidores de beta-Lactamases/farmacologia , Cefalosporinas/metabolismo , Infecções Comunitárias Adquiridas/tratamento farmacológico , Endopeptidases/efeitos dos fármacos , Enterobacteriaceae/efeitos dos fármacos , Enterococcus/efeitos dos fármacos , Aminoaciltransferases/antagonistas & inibidores , Antibacterianos/metabolismo
10.
BMC Infect Dis ; 19(1): 756, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31464593

RESUMO

BACKGROUND: Ventilator-associated pneumonia (VAP) is a well-known, life-threatening disease that persists despite preventative measures and approved antibiotic therapies. This prospective observational study investigated bacterial airway colonization, and whether its detection and quantification in the endotracheal aspirate (ETA) is useful for identifying mechanically ventilated ICU patients who are at risk of developing VAP. METHODS: 240 patients admitted to 3 ICUs at the Lahey Hospital and Medical Center (Burlington, MA) between June 2014 and June 2015 and mechanically ventilated for > 2 days were included. ETA samples and clinical data were collected. Airway colonization was assessed, and subsequently categorized into "heavy" and "light" by semi-quantitative microbiological analysis of ETAs. VAP was diagnosed retrospectively by the study sponsor according to a pre-specified pneumonia definition. RESULTS: Pathogenic bacteria were isolated from ETAs of 125 patients. The most common species isolated was S. aureus (56.8%), followed by K. pneumoniae, P. aeruginosa, and E. coli (35.2% combined). VAP was diagnosed in 85 patients, 44 (51.7%) with no bacterial pathogen, 18 associated with S. aureus and 18 Gram-negative-only cases, and 5 associated with other Gram-positive or mixed species. A higher proportion of patients who were heavily colonized with S. aureus developed VAP (32.4%) associated with S. aureus compared to those lightly colonized (17.6%). The same tendency was seen for patients heavily and lightly colonized with Gram-negative pathogens (30.0 and 0.0%, respectively). Detection of S. aureus in the ETA preceded S. aureus VAP by approximately 4 days, while Gram-negative organisms were first detected 2.5 days prior to Gram-negative VAP. VAP was associated with significantly longer duration of mechanical ventilation and hospitalization regardless of microbiologic cause when compared to patients who did not develop VAP. CONCLUSIONS: The overall VAP rate was 35%. Heavy tracheal colonization supported identification of patients at higher risk of developing a corresponding S. aureus or Gram-negative VAP. Detection of bacterial ETA-positivity tended to precede VAP.


Assuntos
Pneumonia Bacteriana/microbiologia , Pneumonia Associada à Ventilação Mecânica/microbiologia , Respiração Artificial/efeitos adversos , Traqueia/microbiologia , Adulto , Idoso , Antibacterianos/uso terapêutico , Bactérias/isolamento & purificação , Feminino , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Intubação Intratraqueal , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/mortalidade , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Pneumonia Associada à Ventilação Mecânica/mortalidade , Estudos Prospectivos
11.
Eur J Clin Microbiol Infect Dis ; 38(11): 2163-2169, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31372907

RESUMO

To evaluate the effectiveness of trimetoprim-sulfametoxazole (TMP-SMX) for treatment of ventilator-associated pneumonia (VAP). A retrospective cohort study including patients with VAP from 2011 to 2017. Two groups were analysed: TMP-SMX group, including patients who had received TMP-SMX (as first-line and as de-escalation), and No-TMP-SMX group, including patients who had not received TMP-SMX treatment. Primary clinical outcome was mortality at 30 days from starting the antibiotic treatment (T30). Secondary outcomes were mortality at end of treatment (EoT), day survival at T30, and acquisition of multidrug-resistant bacteria during hospitalization in intensive care unit. Eighty cases of VAP were included and devised into two groups: No-TMP-SMX (31/80; 39%) and TMP-SMX (49/80; 61%). Univariate analysis showed no significant differences were found when the TMP-SMX group was compared with the No-TMP-SMX group, except for frequency of male gender (p = 0.025). No significant statistical correlations between mortality at T30 and individual factors were detected by the multivariate model. No cases of either severe allergy or Clostridium difficile disease were reported in the TMP-SMX and No-TMP-SMX groups. TMP-SMX treatment was not associated with higher mortality at EoT and T30 in comparison with the No-TMP-SMX group. TMP-SMX had a good safety profile, in terms of ecology (acquisition of MDR bacteria and Clostridium difficile disease) and clinical management (no allergy events).


Assuntos
Antibacterianos/uso terapêutico , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Idoso , Antibacterianos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos
12.
BMC Infect Dis ; 19(1): 718, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31412809

RESUMO

BACKGROUND: We developed a clinical bedside tool to simultaneously estimate the probabilities of third-generation cephalosporin-resistant Enterobacteriaceae (3GC-R), carbapenem-resistant Enterobacteriaceae (CRE), and multidrug-resistant Pseudomonas aeruginosa (MDRP) among hospitalized adult patients with Gram-negative infections. METHODS: Data were obtained from a retrospective observational study of the Premier Hospital that included hospitalized adult patients with a complicated urinary tract infection (cUTI), complicated intra-abdominal infection (cIAI), hospital-acquired/ventilator-associated pneumonia (HAP/VAP), or bloodstream infection (BSI) due to Gram-negative bacteria between 2011 and 2015. Risk factors for 3GC-R, CRE, and MDRP were ascertained by multivariate logistic regression, and separate models were developed for patients with community-acquired versus hospital-acquired infections for each resistance phenotype (N = 6). Models were converted to a singular user-friendly interface to estimate the probabilities of a patient having an infection due to 3GC-R, CRE, or MDRP when ≥ 1 risk factor was present. RESULTS: Overall, 124,068 patients contributed to the dataset. Percentages of patients admitted for cUTI, cIAI, HAP/VAP, and BSI were 61.6, 4.6, 16.5, and 26.4%, respectively (some patients contributed > 1 infection type). Resistant infection rates were 1.90% for CRE, 12.09% for 3GC-R, and 3.91% for MDRP. A greater percentage of the resistant infections were community-acquired relative to hospital-acquired (CRE, 1.30% vs 0.62% of 1.90%; 3GC-R, 9.27% vs 3.42% of 12.09%; MDRP, 2.39% vs 1.59% of 3.91%). The most important predictors of having an 3GC-R, CRE or MDRP infection were prior number of antibiotics; infection site; infection during the previous 3 months; and hospital prevalence of 3GC-R, CRE, or MDRP. To enable application of the six predictive multivariate logistic regression models to real-world clinical practice, we developed a user-friendly interface that estimates the risk of 3GC-R, CRE, and MDRP simultaneously in a given patient with a Gram-negative infection based on their risk (Additional file 1). CONCLUSIONS: We developed a clinical prediction tool to estimate the probabilities of 3GC-R, CRE, and MDRP among hospitalized adult patients with confirmed community- and hospital-acquired Gram-negative infections. Our predictive model has been implemented as a user-friendly bedside tool for use by clinicians/healthcare professionals to predict the probability of resistant infections in individual patients, to guide early appropriate therapy.


Assuntos
Antibacterianos/uso terapêutico , Infecção Hospitalar/microbiologia , Tomada de Decisões Assistida por Computador , Farmacorresistência Bacteriana/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/microbiologia , Bacteriemia/tratamento farmacológico , Bacteriemia/epidemiologia , Bacteriemia/microbiologia , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Enterobacteriáceas Resistentes a Carbapenêmicos/patogenicidade , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/epidemiologia , Bactérias Gram-Negativas/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/epidemiologia , Hospitais/estatística & dados numéricos , Humanos , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Pneumonia Associada à Ventilação Mecânica/epidemiologia , Pneumonia Associada à Ventilação Mecânica/microbiologia , Sistemas Automatizados de Assistência Junto ao Leito , Prevalência , Probabilidade , Estudos Retrospectivos , Estados Unidos/epidemiologia , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/epidemiologia , Infecções Urinárias/microbiologia , Interface Usuário-Computador
13.
Rev Esp Quimioter ; 32 Suppl 3: 3-10, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31364335

RESUMO

Ceftobiprole, a novel last generation parenteral cephalosporin, has an extended spectrum of activity, notably against methicillin-resistant Staphylococcus aureus (MRSA), ampicillin-susceptible enterococci, penicillin-resistant pneumococci, Enterobacterales and susceptible Pseudomonas aeruginosa. It exerts an inhibitory action on essential peptidoglycan transpeptidases, interfering with cell wall synthesis. The inhibitory action of ceftobiprole through binding to abnormal PBPs like PBP2a in methicillin-resistant staphylococci and PBP2b and PBP2x in the case of ß-lactam-resistant pneumococci, ultimately leads to rapid bacterial cell death. In the case of Enterobacterales, ceftobiprole retains activity against narrow spectrum ß-lactamases but is hydrolysed by their extended-spectrum counterparts, overexpressed Amp C, and carbapenemases. It is also affected by certain efflux pumps from P. aeruginosa. For anaerobic bacteria, ceftobiprole is active against Gram-positive Clostridioides difficile and Peptococcus spp. and Gram-negative Fusobacterium nucleatum but not against Bacteroides group or other anaerobic Gram-negatives. In in vitro studies, a low propensity to select for resistant subpopulations has been demonstrated. Currently, ceftobiprole is approved for the treatment of community-acquired pneumonia and hospital-acquired pneumonia with the exception of ventilator-associated pneumonia. Ceftobiprole's place in therapy appears to lie mainly in its combined activity against Gram-positive organisms, such as S. aureus and S. pneumoniae alongside that against Gram-negative organisms such as P. aeruginosa.


Assuntos
Antibacterianos/farmacologia , Cefalosporinas/farmacologia , Aminoaciltransferases/antagonistas & inibidores , Antibacterianos/metabolismo , Cefalosporinas/metabolismo , Infecções Comunitárias Adquiridas/tratamento farmacológico , Endopeptidases/efeitos dos fármacos , Enterobacteriaceae/efeitos dos fármacos , Enterococcus/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/metabolismo , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Resistência às Penicilinas , Proteínas de Ligação às Penicilinas/antagonistas & inibidores , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/metabolismo , Streptococcus pneumoniae/efeitos dos fármacos , Inibidores de beta-Lactamases/farmacologia
14.
Klin Mikrobiol Infekc Lek ; 25(1): 7-11, 2019 Mar.
Artigo em Tcheco | MEDLINE | ID: mdl-31266087

RESUMO

OBJECTIVES: Ventilator-associated pneumonia (VAP) is the most common nosocomial infection in intensive care patients. The aim of the study was to evaluate the effect of previous antibiotic therapy on the incidence of VAP, mortality and spectrum of bacterial pathogens. MATERIAL AND METHODS: The retrospective, observational study comprised patients over 18 years of age meeting the clinical criteria of VAP. Controls were patients requiring mechanical ventilation for more than 48 hours with no signs of VAP. Each group was divided into two arms according to previous antibiotic therapy. Tracheal aspirates and oropharyngeal swabs were taken from all patients. Cultured isolates were identified using standard microbiological techniques. Antimicrobial susceptibility testing was performed according to the European Committee on Antimicrobial Susceptibility Testing guidelines. In both groups, 28-day mortality, 90-day mortality and multidrug-resistant (MDR) bacterial pathogen frequency were evaluated. RESULTS: The study included 49 patients (32 patients with previous antibiotic therapy, 17 antimicrobial-naive patients). The proportion of individuals with previous antibiotic therapy was significantly lower in VAP patients (34%) than among controls group (66%; p = 0.02). The VAP criteria were met by 23 patients (11 with previous antibiotic therapy, 12 without the therapy). The Enterobacteriaceae including extended-spectrum beta-lactamase-producing strains and Pseudomonas aeruginosa were the most common pathogens isolated. MDR pathogens were statistically significantly more frequent in patients with previous antibiotic therapy (77% vs. 33%; p = 0.047). In patients with previous antibiotic therapy, 28-day mortality was lower (18%; n = 2) than in antimicrobial-naïve patients (33%, n = 4; p = 0.640). The difference was more pronounced in 90-day mortality, albeit with low statistical significance (18%, n = 2 vs. 58%, n = 7; p = 0.089). CONCLUSIONS: Previous antibiotic therapy was associated with a lower incidence of VAP and a higher frequency of MDR bacterial pathogens. VAP antibiotic therapy modified according to knowledge of previous antibiotic therapy and cultured isolates was correlated with lower 28-day and 90-day mortality rates.


Assuntos
Anti-Infecciosos , Pneumonia Associada à Ventilação Mecânica , Adolescente , Adulto , Anti-Infecciosos/uso terapêutico , República Tcheca/epidemiologia , Farmacorresistência Bacteriana Múltipla , Humanos , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Pneumonia Associada à Ventilação Mecânica/epidemiologia , Estudos Retrospectivos
15.
J Microbiol Immunol Infect ; 52(5): 788-795, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31155463

RESUMO

BACKGROUND: Doripenem shows good in vitro activity against common nosocomial pathogens, such as extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii. However, the use of doripenem for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) remains controversial. The aim of this study was to compare the efficacy and safety between doripenem and meropenem for patients with HAP or VAP. METHODS: Adult patients diagnosed with HAP and VAP at National Taiwan University Hospital, who received doripenem or meropenem for more than 48 h between January 2015 and November 2017, were retrospectively reviewed. All-cause mortality on the 30th day was used as the primary outcome measurements. RESULTS: Fifty-seven patients with doripenem and 252 patients with meropenem were analyzed. Compared to the meropenem group, the doripenem group was younger and had a higher Sequential Organ Failure Assessment (SOFA) score. Multivariable Cox regression analysis revealed that presence of solid organ malignancies (adjusted hazard ratio [AHR], 1.82; 95% CI, 1.04-3.19, p = 0.003) and SOFA score (AHR, 1.10; 95% CI, 1.03-1.17, p = 0.003) were independent factors associated with mortality. There was no survival difference of 30-day mortality between patients receiving doripenem and meropenem for HAP or VAP (log-rank p = 0.113). However, a poorer outcome was observed among patients with hematological disease in the doripenem group (log-rank p = 0.012). CONCLUSION: Our results demonstrate that doripenem has similar efficacy as meropenem in HAP or VAP patients. With an aim to enhance antibiotic diversity, doripenem could be an alternative choice for patients with HAP or VAP, except for those with hematological malignancies.


Assuntos
Antibacterianos/uso terapêutico , Infecção Hospitalar/tratamento farmacológico , Doripenem/uso terapêutico , Meropeném/uso terapêutico , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Acinetobacter baumannii/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Feminino , Hospitais , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Análise Multivariada , Pneumonia Associada à Ventilação Mecânica/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Análise de Regressão , Estudos Retrospectivos , Taiwan
16.
PLoS One ; 14(6): e0218372, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31220122

RESUMO

Seven hospitals participated in the Dutch national surveillance for ventilator-associated pneumonia (VAP) and its risk factors. We analysed time-independent and time-dependent risk factors for VAP using the standard Cox regression and the flexible Weighted Cumulative Effects method (WCE) that evaluates both current and past exposures. The prospective surveillance of intensive care patients aged ≥16 years and ventilated ≥48 hours resulted in the inclusion of 940 primary ventilation periods, comprising 7872 ventilation days. The average VAP incidence density was 10.3/1000 ventilation days. Independent risk factors were age (16-40 years at increased risk: HR 2.42 95% confidence interval 1.07-5.50), COPD (HR 0.19 [0.04-0.78]), current sedation score (higher scores at increased risk), current selective oropharyngeal decontamination (HR 0.19 [0.04-0.91]), jet nebulizer (WCE, decreased risk), intravenous antibiotics for selective decontamination of the digestive tract (ivSDD, WCE, decreased risk), and intravenous antibiotics not for SDD (WCE, decreased risk). The protective effect of ivSDD was afforded for 24 days with a delay of 3 days. For some time-dependent variables, the WCE model was preferable over standard Cox proportional hazard regression. The WCE method can furthermore increase insight into the active time frame and possible delay herein of a time-dependent risk factor.


Assuntos
Antibacterianos/uso terapêutico , Infecção Hospitalar/epidemiologia , Pneumonia Associada à Ventilação Mecânica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Adolescente , Idoso , Infecção Hospitalar/etiologia , Feminino , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/patologia , Humanos , Inalação , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Pneumonia Associada à Ventilação Mecânica/patologia , Modelos de Riscos Proporcionais , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/patologia , Respiração Artificial/efeitos adversos , Fatores de Risco
17.
Eur J Pharm Sci ; 136: 104940, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31132402

RESUMO

BACKGROUND: Ventilator-associated pneumonia (VAP) caused by multidrug-resistant (MDR) Acinetobacter baumannii remains one of the leading causes of the high mortality rate in critically ill patients. Sulbactam has been considered as an alternative concomitant medication with other effective antimicrobial agents for the treatment of these MDR microorganisms. The aims of this study were (i) to characterize the population pharmacokinetics (PK) and (ii) to assess the efficacy of various dosage regimens of sulbactam in terms of probability of target attainment (PTA). METHODS: The PK studies were carried out following administration of 2 g of sulbactam every 12 h on the 7th dose of drug administration in 16 patients with VAP, and a Monte Carlo simulation was performed to determine the PTA of achieving 40% and 60% the exposure time during which the total plasma drug concentration remained above the MIC (T>MIC). RESULTS: The volume of distribution and total clearance of sulbactam were 22.17 ±â€¯1.60 L and 6.76 ±â€¯2.37 L/h, respectively. For pathogens with a MIC of 8 µg/mL, the high PTAs of achieving (≥90%) 60% T>MIC in patients with serum albumin 1.7-2.4 g/dL and CLCR 90-120 mL/min following administration of sulbactam as a 4-h infusion of 1 g every 6 h, 2 g every 12 h, and 2 g every 8 h were 98.65%, 78.07% and 98.23%, respectively. For pathogens with a MIC of 16 µg/mL, the high PTAs of achieving (≥90%) 60% T>MIC in patients with serum albumin 1.7-2.4 g/dL and CLCR 90-120 mL/min following administration of sulbactam as a 4-h infusion of 2 g every 6 h, and 3 g every 8 h were 98.83% and 95.59%, respectively. CONCLUSION: These findings indicate that high dosage combination regimens are required for the treatment of life-threatening infections in critically ill patients with VAP.


Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacocinética , Antibacterianos/uso terapêutico , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Sulbactam/farmacocinética , Sulbactam/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Estado Terminal , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana/métodos , Pessoa de Meia-Idade , Método de Monte Carlo , Pneumonia Associada à Ventilação Mecânica/microbiologia , Adulto Jovem
18.
Pediatr Crit Care Med ; 20(8): 697-706, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30985606

RESUMO

OBJECTIVES: To develop a guideline for the decision to continue or stop antibiotics at 48-72 hours after their initiation in children with suspected ventilator-associated infection. DESIGN: Prospective, multicenter observational data collection and subsequent development of an antibiotic guideline. SETTING: Twenty-two PICUs. PATIENTS: Children less than 3 years old receiving mechanical ventilation who underwent clinical testing and initiation of antibiotics for suspected ventilator-associated infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Phase 1 was a prospective data collection in 281 invasively ventilated children with suspected ventilator-associated infection. The median age was 8 months (interquartile range, 4-16 mo) and 75% had at least one comorbidity. Phase 2 was development of the guideline scoring system by an expert panel employing consensus conferences, literature search, discussions with institutional colleagues, and refinement using phase 1 data. Guideline scores were then applied retrospectively to the phase 1 data. Higher scores correlated with duration of antibiotics (p < 0.001) and higher PEdiatric Logistic Organ Dysfunction 2 scores (p < 0.001) but not mortality, PICU-free days or ventilator-free days. Considering safety and outcomes based on the phase 1 data and aiming for a 25% reduction in antibiotic use, the panel recommended stopping antibiotics at 48-72 hours for guideline scores less than or equal to 2, continuing antibiotics for scores greater than or equal to 6, and offered no recommendation for scores 3, 4, and 5. The acceptability and effect of these recommendations on antibiotic use and outcomes will be prospectively tested in phase 3 of the study. CONCLUSIONS: We developed a scoring system with recommendations to guide the decision to stop or continue antibiotics at 48-72 hours in children with suspected ventilator-associated infection. The safety and efficacy of the recommendations will be prospectively tested in the planned phase 3 of the study.


Assuntos
Antibacterianos/uso terapêutico , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Guias de Prática Clínica como Assunto , Respiração Artificial/efeitos adversos , Conferências de Consenso como Assunto , Esquema de Medicação , Feminino , Humanos , Lactente , Unidades de Terapia Intensiva Pediátrica/estatística & dados numéricos , Masculino , Estudos Prospectivos
19.
Artigo em Inglês | MEDLINE | ID: mdl-30962339

RESUMO

Ertapenem provides activity against many pathogens commonly associated with hospital-acquired and ventilator-associated bacterial pneumoniae (HABP and VABP, respectively), including methicillin-susceptible Staphylococcus aureus and numerous Gram-negative pathogens with one major gap in coverage, Pseudomonas aeruginosa Pharmacokinetic-pharmacodynamic (PK-PD) target attainment analyses were conducted to evaluate ertapenem against the most prevalent Enterobacteriaceae causing HABP/VABP. The objective of these analyses was to provide dose selection support for and demonstrate the appropriateness of ertapenem to empirically treat patients with HABP/VABP when administered with murepavadin, a novel targeted antimicrobial exhibiting a highly specific spectrum of activity against P. aeruginosa A previously developed population pharmacokinetic model, a total-drug epithelial lining fluid (ELF) to free-drug serum penetration ratio, contemporary in vitro surveillance data for ertapenem against Enterobacteriaceae, and percentage of the dosing interval for which drug concentrations exceed the MIC value (%T>MIC) targets associated with efficacy were used to conduct Monte Carlo simulations for five ertapenem regimens administered over short or prolonged durations of infusion. Overall total-drug ELF percent probabilities of PK-PD target attainment based on a %T>MIC target of 35% among simulated patients with HABP/VABP arising from Enterobacteriaceae based on pathogen prevalence data for nosocomial pneumonia ranged from 89.1 to 92.7% for all five ertapenem regimens evaluated. Total-drug ELF percent probabilities of PK-PD target attainment ranged from 99.8 to 100%, 97.9 to 100%, 10.6 to 74.1%, and 0 to 1.50% at MIC values of 0.06, 0.12, 1, and 4 µg/ml, respectively (MIC90 values for Escherichia coli, Serratia marcescens, Enterobacter species, and Klebsiella pneumoniae, respectively). Results of these analyses provide support for the evaluation of ertapenem in combination with murepavadin for the treatment of patients with HABP/VABP.


Assuntos
Antibacterianos/farmacocinética , Antibacterianos/uso terapêutico , Ertapenem/farmacocinética , Ertapenem/uso terapêutico , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Bactérias/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana
20.
J Chemother ; 31(4): 202-208, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30990368

RESUMO

Effective treatment approaches for biofilms in endotracheal tubes (ETTs) are lacking. In this study, we evaluated the in vitro effects of five antimicrobials against biofilms formed by Klebsiella pneumoniae in ETTs. K. pneumoniae was added to minimal mucin medium prior to inoculation in microtiter plates containing ETT fragments. Biofilm susceptibility was assessed by crystal violet staining. At 24 h, the antimicrobials significantly reduced biofilm formation. At 48 h, all of the antimicrobial agents exhibited significant reductions in biofilm formation, even at concentrations above the minimum inhibitory concentration (MIC). Tigecycline and fosfomycin showed the greatest inhibition capacity, with good activity at concentrations twofold greater than the MIC. K. pneumoniae exhibited excellent biofilm formation ability, with formation in the first 24 h and significantly reduced antimicrobial activity. These results contribute to the establishment of new antibiotic breakpoints for the adequate management of infections associated with biofilm formation. Abbreviations ETT Endotracheal tube MIC Minimum inhibitory concentration MBIC Minimum biofilm inhibitory concentration OD Optical density PBS Phosphate-buffered saline VAP Ventilator-associated pneumonia.


Assuntos
Anti-Infecciosos/farmacologia , Biofilmes/efeitos dos fármacos , Intubação Intratraqueal/efeitos adversos , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/efeitos dos fármacos , Humanos , Infecções por Klebsiella/microbiologia , Testes de Sensibilidade Microbiana/métodos , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Pneumonia Associada à Ventilação Mecânica/microbiologia
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