Rev Esp Quimioter 2017, Mar 29

Ceftolozane-tazobactam for the treatment of ventilator-associated infections by colistin-resistant Pseudomonas aeruginosa                     

FRANCISCO ÁLVAREZ LERMA, ROSANA MUÑOZ BERMÚDEZ, SANTIAGO GRAU, MARÍA PILAR GRACIA ARNILLAS, LUISA SORLI, LLUIS RECASENS, MIQUEL MICO GARCÍA           

The use of colistin for the treatment of multiresistant bacteria has led to the emergence of colistin-resistant strains of Gram-negative bacilli. Treatment of infections caused by these pan–drug-resistant bacteria is difficult owing to the paucity of effective antibiotics. We report two cases of ventilator-associated respiratory infection caused by pan–drug-resistant, colistin-resistant Pseudomonas aeruginosa that were successfully treated with ceftolozane-tazobactam.

Rev Esp Quimioter 2017; Mar 29 [pdf]

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Rev Esp Quimioter 2015:28(1):47-53

A practice-based observational study identifying factors associated with the use of high-dose tigecycline in the treatment of secondary peritonitis in severely ill patients                                 
 


EMILIO MASEDA, ALEJANDRO SUÁREZ-DE-LA-RICA, VÍCTOR ANILLO, PATRICIA SALGADO,
EDUARDO TAMAYO, CARLOS A. GARCÍA-BERNEDO, FERNANDO RAMASCO, MARÍA-JOSÉ VILLAGRÁN, ARACELI LÓPEZ-TOFIÑO, MARÍA-JOSÉ GIMÉNEZ, JUAN-JOSÉ GRANIZO, CARMEN HERNÁNDEZ-GANCEDO, LORENZO AGUILAR, FERNANDO GILSANZ              

 

Introduction. Based on tigecycline linear pharmacokinetic/pharmacodynamics, dose increases have been advocated to maximise activity especially when severe infections with high bacterial load and/or multidrug resistance are suspected. This practice-based observational study explored factors associated with tigecycline administration (100 mg/12h, 200 mg loading dose) in severely ill patients with complicated intra-abdominal infection (cIAI) admitted to four Surgical Critical Care Units (SCCUs).
Methods. Medical records of all consecutive adult patients with cIAI and controlled infection source requiring surgery and admission for ≥48h to SCCU were reviewed and divided into patients treated with a regimen including tigecycline (tigecycline group) and those that not (control group). A logistic regression model was performed using “tigecycline administration” (dependent variable) and variables showing differences (p≤0.1) in bivariate analyses (independent variables).
Results. One hundred and twenty one patients were included. In the tigecycline group, higher percentage of patients(vs. controls) presented colon as surgical site (66.7% vs. 41.8%, p=0.006), nosocomial infection (55.6% vs. 26.9%, p=0.001), mechanical ventilation (48.1% vs. 28.4%, p=0.025), chronic renal replacement therapy (40.7% vs. 19.4%, p=0.008), septic shock (72.2% vs. 46.3%, p=0.004), and higher values of SAPS II (48.0±15.0 vs. 39.6±15.5, p=0.003), SOFA at admission (7.0±3.3 vs. 5.5±3.7, p=0.020), lactate-24h (2.5±2.8 vs. 1.6±0.9, p=0.029) and CRP-72h (207.4±87.9 vs. 163.7±76.8, p=0.021). In the multivariate analysis (R2=0.187, p<0.001) nosocomial infection (OR=7.721; 95%CI=2.193, 27.179; p=0.001), colon as infection site (OR=4.338; 95%CI=1.432, 13.145; p=0.009) and CRP-72h (OR=1.009 per-unit; 95%CI=1.002, 1.016; p=0.012) were associated with tigecycline administration.
Conclusions. In severely ill patients with cIAI, high-dose tigecycline administration was associated with nosocomial origin of cIAI and colon as source infection site.

Rev Esp Quimioter 2015:28(1):47-53 [pdf]

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Rev Esp Quimioter 2015:28(4):200-206

Maraviroc modifies gut microbiota composition in a mouse model of obesity: a plausible therapeutic option to prevent metabolic disorders in HIV-infected patients                                 
 

PATRICIA PÉREZ-MATUTE, LAURA PÉREZ-MARTÍNEZ, JAVIER AGUILERA-LIZARRAGA, JOSÉ R. BLANCO, JOSE A. OTEO              

Introduction. The proportion of HIV-infected patients with overweight/obesity has increased in recent years. These patients have an increased metabolic/cardiovascular risk compared with non-obese patients. Modulation of gut microbiota composition arises as a promising tool to prevent the develop-ment of obesity and associated disorders. The aim of this study was to investigate the impacts of maraviroc (MVC), a CCR5 antagonist approved for clinical use in HIV-infected patients, on gut microbiota composition in a mouse model of obesity.
Methods. Thirty two male C57BL/6 mice were assigned to:a) Control (chow diet), b) MVC (chow diet plus 300 mg/L MVC), c) High-fat diet (HFD) or d) HFD/MVC (HFD plus 300 mg/L MVC) groups. Body weight and food intake was recorded every 2-3 days. Mice were euthanized after 16 weeks of treatment and cecal contents were removed to analyse by real-time PCR four bacterial orders from the most dominant phyla in gut.
Results. Mice fed with a HFD showed a significant increase in Enterobacteriales (p<0.001 vs. control). MVC treatment induced a significant decrease in control (p<0.05) and HFD fed mice (p<0.001). Interestingly, this order was positively associated with body weight gain, insulin resistance and fatty liver. HFD induced a significant decrease in Bacteroidales and Clostridiales levels (p<0.05 and p<0.01, respectively). MVC decreased the presence of Bacteroidales (p<0.05 vs. control) while an increase was observed in HFD/MVC mice (p=0.01 vs. HFD). No direct effects of MVC were observed on Clostridiales and Lactobacillales.
Conclusions. MVC may constitute a new therapeutic option to prevent obesity and related disorders in HIV-infected patients.

Rev Esp Quimioter 2015:28(4):200-206 [pdf]

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Rev Esp Quimioter 2015:28(Suppl. 1):52-53

Optimization strategies in management of CMV infection in transplant patients     

                        
 DAVID NAVARRO              

Currently, two therapeutic strategies are applied for preventing the development of CMV end-organ disease in transplant recipients: universal prophylaxis and preemptive antiviral therapy. Both are potentially optimable. As for the former strategy,  precisely identifying patients at greatest risk of viremia would allow for a targeted prophylaxis. In this sense several genotypic, immunological and biological markers have been described that could be ancillary to that purpose. As for the latter strategy, combined monitoring of plasma CMV DNA load and peripheral levels of CMV-specific CD8 + and CD4 + IFN-γ producing T cells would permit a more rationale use of antivirals, thus avoiding overtreatment and derived toxicity.

Rev Esp Quimioter 2015:28(Suppl. 1):52-53 [pdf]

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Rev Esp Quimioter 2016,29(1):32-39

Intraabdominal candidiasis in surgical ICU patients treated with anidulafungin: A multicenter retrospective study     

                        
EMILIO MASEDA, MARTA RODRÍGUEZ-MANZANEQUE, DAVID DOMINGUEZ, MATILDE GONZÁLEZ-SERRANO, LORENA MOURIZ, JULIÁN ÁLVAREZ-ESCUDERO, NAZARIO OJEDA, PURIFICACIÓN SANCHEZ-ZAMORA, JUAN-JOSÉ GRANIZO, MARÍA-JOSÉ GIMÉNEZ, ON BEHALF OF THE PERI-OPERATIVE INFECTION WORKING GROUP OF THE SPANISH SOCIETY OF ANESTHESIOLOGY AND CRITICAL CARE              

Introduction. Patients with recent intraabdominal events are at uniquely risk for intraabdominal candidiasis (IAC). Candida peritonitis is a frequent and life-threatening complication in surgically ill patients. International guidelines do not specifically address IAC. This study describes clinical features of IAC in critical patients treated with anidulafungin in Surgical ICUs (SICUs).
Material and methods. A practice-based retrospective study was performed including all adults with IAC admitted to 19 SICUs for ≥24h treated with anidulafungin. IAC was documented (Candida isolation from blood/peritoneal fluid/abscess fluid and/or histopathological confirmation) or presumptive (host factors plus clinical criteria without mycological support). Total population and the subgroup of septic shock patients were analyzed.
Results. One hundred and thirty nine patients were included, 94 (67.6%) with septic shock, 112 (86.2%) after urgent surgery. Of them, 77.7% presented peritonitis and 21.6% only intraabdominal abscesses. Among 56.8% cases with documented IAC, C. albicans (52.8%) followed by C. glabrata (27.8%) were the most frequent species. Anidulafungin was primarily used as empirical therapy (59.7%), microbiologically directed (20.9%) and anticipated therapy (15.8%). Favourable response was 79.1% (76.6% among patients with septic shock). Intra-SICU mortality was 25.9% (28.7% among patients with septic shock).
Conclusions. Among IACs managed at SICUs, peritonitis was the main presentation, with high percentage of patients presenting septic shock. C. albicans followed by C. glabrata were the main responsible species. Anidulafungin treatment was mostly empirical followed by microbiologically directed therapy, with a favourable safety profile, even among patients with septic shock.

Rev Esp Quimioter 2016;29(1):32-39 [pdf]

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Rev Esp Quimioter 2016, 29(3):146-150

Uropathogen pattern and antimicrobial susceptibility in positive urinary cultures isolates from paediatric patients   

                    
VANESSA MOYA-DIONISIO, MIKEL DÍAZ-ZABALA, ALEIDA IBÁÑEZ-FERNÁNDEZ, PILAR SUÁREZ-LEIVA, VENANCIO MARTÍNEZ-SUÁREZ, FLOR ÁNGEL ORDÓÑEZ-ÁLVAREZ, FERNANDO SANTOS- RODRÍGUEZ             

Introduction. Knowledge of urophatogens and antibiotic susceptibility should be used to assist with empirical urinary tract infection treatment.
Material and methods. We retrospectively analysed local bacterial pattern and antimicrobial susceptibility in positive urinary isolates from paediatric patients collected in the period 2009-2013. Results were compared with a previous study carried out in the same sanitary area between 1995 and 1999.
Results. We identified 2,762 urinary isolates. Escherichia coli was the most common uropathogen (58.9%), followed by Enterococcus sp. (11.6%) and Proteus mirabilis (10.9%). More than 95% of non extended-spectrum beta-lactamase (ESBL)-producing E. coli were susceptible to nitrofurantoin, fosfomycin, cefotaxime and aminoglycosides. However, 56%, 49%, and 22% of the E. coli isolates were resistant to ampicillin, oral first-generation cephalosporins, and trimethoprim-sulfamethoxazole, respectively. Ampicillin and amoxicillin-clavulanate were the most effective antibiotics to treat Enterococcus sp. and P. mirabilis, respectively. Not significant modifications were found compared to results published at the same area in the ‘90s.
Conclusions.  E. coli was the mostly isolated uropathogen, with a high percentage of resistance to ampicillin, oral first-generation cephalosporins, and trimethoprim-sulfamethoxazole. These urinary isolates and antimicrobial susceptibility patterns were similar to those reported in other paediatric studies and did not show significant changes compared to local previously published results. Thus, it can be considered that the current recommendations about empiric antibiotic therapy in paediatric urinary tract infections remain applicable nowadays.

Rev Esp Quimioter 2016; 29(3):146-150 [pdf]

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Rev Esp Quimioter 2016, 29(5):244-248

About microbiological methods for detection of oxacillin resistance in coagulase-negative staphylococci                     

MIGUEL FAJARDO, ROCÍO HIDALGO, JORGE GAITÁN, ROSA SÁNCHEZ-SILOS, PALOMA MARTÍN-CORDERO          

Introduction. Coagulase-negative staphylococci (CoNS) take part of the human skin and mucous membranes, but they are also involving in infections with the increasing use of prosthetic, indwelling devices or intravascular catheter-related bacteraemia. They are more resistance than Staphylococcus aureus against a wide range of antimicrobial agents, and it have been observed an increase in morbidity and mortality of patients with incorrect treatment.
Material and methods. To analyze the results obtained by different commercial techniques: two automatic microdilution systems (MicroScan and Vitek2 Compact), PBP2a agglutiation test, with and without 1 μg oxacillin disk induction, and detection of mecA gene by nucleic acids amplification techniques, for the diagnosis of methicillin resistance staphylococci in 170 strains of CoNS isolated from blood cultures.
Results. One hundred and seventy methicillin resistance staphylococci were detected by MicroScan, 167 strains by Vitek 2 Compact, 115 strains were PBP2a positive without oxacillin induction and 168 after oxacillin induction. Finally, 167 strains were mecA gene positive detected by nucleic acids amplification techniques.
Conclusions. It is necessary to do oxacillin induction before PBP2a test to avoid false negatives. There are a great variability in the phenotypic expression of methicillin resistance in CoNS.

Rev Esp Quimioter 2016; 29(5):244-248 [pdf]

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Rev Esp Quimioter 2016, 29(Suppl. 1):72-75

Resistance to the antimalarial drugs                     

EMMANUELE VENANZI, ROGELIO LÓPEZ-VÉLEZ          

Malaria is one of the most widespread infectious diseases around the world with 214 million cases and 438,000 deaths in 2015. In the early twentieth century it was described for the first time the resistance to quinine and, since then, drug resistance to antimalarial drugs has spread up to represent a global challenge in the fight and control of malaria. Understanding the mechanisms, geography and monitoring tools that we can act against resistance to antimalarial drugs is critical to prevent its expansion.

Rev Esp Quimioter 2016; 29(Suppl. 1):72-75 [pdf]

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Rev Esp Quimioter 2017; 30(1):14-18

Assessment of antibiotic prophylaxis adequacy in rectal surgery                    

JUAN ANTONIO DEL-MORAL-LUQUE, ENRIQUE COLÁS-RUIZ, PABLO GIL-YONTE, JOSÉ MARÍA FERNÁNDEZ-CEBRIÁN, MARÍA CONCEPCIÓN VILLAR-DEL-CAMPO, ALBERTO DELGADO-IRIBARREN, JOSÉ FRANCISCO VALVERDE-CÁNOVAS, GIL RODRÍGUEZ-CARAVACA           

Introduction. Antibiotic prophylaxis is the most suitable tool for preventing surgical site infection (SSI), so the development of guidelines and assessment of its monitoring is essential. In this study protocol compliance of antibiotic prophylaxis in rectal surgery and the effect of its adequacy in terms of pre-ention of SSI was assessed.
Material and methods. Prospective cohort study was conducted from 1 January 2009 to 30 December 2015. The degree of compliance with antibiotic prophylaxis and causes of non-compliance in rectal surgery was evaluated. The incidence of SSI was studied after a maximum period of 30 days of incubation. To assess the effect of prophylaxis non-compliance on SSI the relative risk (RR) adjusted with the aid of a logistic regression model was used.
Results. The study covered a total of 244 patients. The patients infected reached 20 cases with a SSI cumulative incidence of 8.2% (CI95%: 4.8-11.6). Antibiotic prophylaxis was indicated in all patients and was administered in 98% of cases, with an overall protocol compliance 92.5%. The principal cause of non-compliance was the choice of antibiotic 55.6% (n=10). The effect of inadequacy of antibiotic prophylaxis on surgical infection was RR=0.58, CI95%: 0.10-4.10 (P>0.05).
Conclusions. Compliance with antibiotic prophylaxis was high. No relationship between the adequacy of prophylaxis and incidence of surgical site infection in rectal surgery was found.

Rev Esp Quimioter 2017; 30(1):14-18  [pdf]

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Rev Esp Quimioter 2017, Mar 29

A rapid validated UV-HPLC method for the simultaneous determination of the antiretroviral compounds darunavir and raltegravir in their dosage form                     

GABRIEL ESTAN-CEREZO, ANA GARCÍA-MONSALVE, LETICIA SORIANO-IRIGARAY, FRANCISCO JOSÉ RODRÍGUEZ-LUCENA, ANDRÉS NAVARRO-RUIZ           

Introduction. A rapid, simple and sensitive high-performance liquid chromatography (HPLC) method with ultraviolet detection has been developed for quantification of darunavir and raltegravir in their pharmaceutical dosage form.
Material and methods. The assay enables the measurement of both drugs with a linear calibration curve (R2= 0.999) over the concentration range 5–100 mg/L. The determination was performed on an analytical Tracer Excel 120 ODSB (15×0.4.6 cm) column at 35ºC. The selected wavelength was 254 nm. The mobile phase was a mixture of 0.037 M sodium dihydrogen phosphate buffer, acetonitrile and methanol (40:50:10, v/v/v) at a flow rate of 2.0 mL/min Nevirapine (50 mg/L) was used as internal standard.
Results. Accuracy, intra-day repeatability (n = 5), and inter-day precision (n = 3) were found to be satisfactory, being the accuracy  from -4.33 to 3.88% and precisions were intra-day and inter-day, 0.25% and 4.42% respectively in case of darunavir. Raltegravir intra-day and inter-day precisions lower of 1.01 and 2.36%, respectively and accuracy values bet from -4.02 to 1.06%.
Conclusions. Determination of the darunavir and raltegravir in their dosage form was done with a maximum deviation of 4%. This analytical method is rapid, easily implantable and offers good results..

Rev Esp Quimioter 2017; Mar 29 [pdf]

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