Rev Esp Quimioter 2010:23(1):4-11

Nonantimicrobial effects of tetracyclines

L. GARCÍA-ÁLVAREZ, J. A. OTEO

 

Tetracyclines are a family of antibiotics very common in clinical practice that have been used in not infectious affections. One of their most studied actions is their ability to inhibit matrix metalloproteinases (MMPs), a group of proteinases that have been implicated in pathological processes as oncogenesis and inflammation. Tetracyclines have been shown to play an important role in malignant angiogenesis and cancer invasion, which is related with tumor aggressiveness and metastatic potential. They also show anti-inflammatory activity in neurological, respiratory, bone and heart diseases, and in rheumatologic and dermatologic processes. The aim of this review is to make an updating about the non antimicrobial actions of tetracyclines, specially their therapeutic applications in different diseases.

 
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Rev Esp Quimioter 2010:23(1):12-19

Multidrug resistant Acinetobacter baumanii: clinical update and new highlights

A. HERNÁNDEZ, E. GARCÍA, G. YAGÜE, J. GÓMEZ 

 

The role of multidrug resistant Acinetobacter baumanii and its clinical relevance have been recently appreciated as a ubiquitous opportunistic nosocomial pathogen. Risk factors associated with A. baumanii infection include severe underlying diseases, previous surgery, invasive procedures, treatment with broad-spectrum antibiotics, length of hospital stay, admission to intensive care units (ICU). Carbapenem-multidrug resistant A. baumanii infections are probably associated to greater severity and more complications; in our cohort mortality was 49.3% and related mortality (within 72 hours) was 10.39%. However, severe underlying diseases probably play an important role in the clinical outcome of patients with MDR-C A. baumanii infection and controversy exists regarding the real mortality attributable to antimicrobial resistance because a high proportion of deaths took place > 7 days after diagnosis. Nevertheless, in our experience, carbapenem resistance, inappropriate therapy and monotherapy are associated to a higher mortality. Special attention should be paid to design well-controlled prospective clinical trials to determine the optimal antimicrobial therapy in critically ill patients suspected of having MDR Acinetobacter infection.

 
Rev Esp Quimioter 2010:23(1):12-19 [pdf]

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Rev Esp Quimioter 2010:23(1):20-26

Pseudomonas aeruginosa: antimicrobial resistance in clinical isolates. Castellón 2004 -2008

F. J. PARDO, M. D. TIRADO, E. D. GARCÍA, J. GRANADOS, A. CAMPOS, R. MORENO 

 

Retrospective study of antimicrobial susceptibility of 1.943 Pseudomonas aeruginosa clinical isolates to amikacin, tobramycin, gentamicin, ceftazidime, cefepime, meropenem, piperacillin-tazobactam and ciprofloxacin during a five year period. The percentage of resistance went from 2.07% to amikacin from 15.89% to ciprofloxacin. These percentages showed differences depending on the extra or intrahospitalary origin, departments and samples. Isolates from hospital patients were significantly more resistant than the ones from ambulatory patients (p≤0.001:tobramycin, 13.74% vs 5.05%; gentamicin, 13.74% vs 8.26%; ceftazidime, 12.67% vs 4.24%; cefepime, 11.48% vs 7.07%; meropenem, 8.57% vs 2.06%),except for amikacin (1.98% vs 2.2%, p=0.74), piperacillin/tazobactam (6.07% vs 4.55%, p=0.14) and ciprofloxacin (17.17% vs 13.97%, p=0.06). Critical care department and respiratory samples showed the highest resistance percentages while surgery department and invasive samples showed the lowest. Multidrug-resistance was found in 4.8% of the isolates. When comparing our data with those from our previous study (1992-2003), we observed a significant reduction in antibiotic resistance to amikacin (7.74% vs 2.07%, p<0.001), tobramycin (13.61% vs 10.26%, p<0.001), gentamicin (30,85% vs 14.73%, p<0,001), ceftazidime (14.63% vs 9,28%, p<0.001), cefepime (12,31% vs 9.71%, p=0.005), and meropenem (7.74% vs 2.07%, p=0.001); and there were no changes in resistance to piperacillin- tazobactam (4.26% vs 5.46%, p=0,06) and ciprofloxacin (16.02% vs 15.89%, p=0.89). In the last years, the susceptibility pattern of P. aeruginosa to antimicrobial agents has changed in our health district, and it is very different from the one described in national studies so it would be very important to monitore susceptibility of clinical isolates periodically.

 
Rev Esp Quimioter 2010:23(1):20-26 [pdf]

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Rev Esp Quimioter 2010:23(1):27-35

Linezolid more efficacious than vancomycin to eradicate infecting organism in critically ill patients with Gram-positive infections

J. M. SIRVENT, L. PIÑEIRO, M. DE LA TORRE, M. MOTJÉ, J. DE BATLLE, A. BONET

 

Objetive: A prospective and observational study has been conducted to analyze the efficacious of linezolid compared to vancomycin to eradicate the infecting organism in critically ill patients with Gram-positive infections.
Patients and Methods: Prospective, observational and non-controlled study in a medical-surgical intensive care unit (ICU) in a university hospital. A total number of 53 critically ill patients with therapy to proven Grampositive bacterial infection were studied. Infected patients were diagnosed and treated according to international guidelines, following standard protocol for the critically ill infected patients. Microbiologic eradication of the infecting organism at the seventh day of treatment and patients’ clinical outcome were analysed.
Results: Twenty-seventh patients received linezolid and twenty-six received vancomycin. Infection-site diagnoses were: hospital-acquired pneumonia (21 cases: 39.6%), complicated surgical-site infection (19 cases: 35.8%) and catheter-related bacteraemia (13 cases: 24.5%).The most important isolated microorganism was methicillin-resistant Staphylococcus aureus (MRSA) (28 cases:52.8%). Clinical success was 20/27 (74.1%) in the linezolid group and 16/26 (61.5 %) in the vancomycin group, with p= 0.3. The adjusted logistic regression model demonstrated that the treatment with linezolid is associated to microbiologic eradication of the infecting organism at the seventh day of treatment [OR = 7.88 (95% CI 1.86-33.52)] and p = 0.005. In this model, the length of hospital stay was lower in the group with microbiologic eradication at the seventh day (p = 0.015). Drug-related adverse events were comparable in both groups of treatment.
Conclusion: Treatment with linezolid in critically ill patients with Gram-positive infections was equivalent to vancomycin in terms of efficacy and safety, but linezolid was associated to a higher rate of microbiologic eradication of the infecting organism at the seventh day of treatment.

 
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Rev Esp Quimioter 2010:23(1):36-42

Changes in the antimicrobial susceptibility of Escherichia coli isolates from community diagnosed urinary tract infections during the period 2003-2007. Multicentre study in Castilla la Mancha (Spain)

D. TENA, A. GONZÁLEZ-PRAETORIUS, J. C. GONZÁLEZ, E. HEREDERO, S. ILLESCAS, C. SAINZ DE BARANDA, G. SESEÑA

 

Objective: To know the evolution of susceptibility patterns of Escherichia coli in patients with communitydiagnosed urinary tract infections (UTIs) during last years in Castilla la Mancha (Spain).
Methods: Descriptive and retrospective study performed between january 2003 and december 2007. We studied data about frequency and susceptibility of 33.651 E. coli isolates from urine cultures that were remited from primary care centres depending of 6 hospitals in Castilla la Mancha (Spain).
Results: Susceptibility rates of E. coli for most antibiotics decreased significantly during the 5-year period, especially for amoxicillin-clavulanic acid, cefuroxime and quinolones. Average rates of susceptibility for amoxicillin- clavulanic acid, ciprofloxacin, cefuroxime, fosfomycin and nitrofurantoin were: 86,7, 75,4, 87,3, 97,6 and 96,2%, respectively. We observed a significantly increase of E. coli isolates producing extended-spectrum betalactamases (ESBLs), from 1,9% in 2003 to 4,9% in 2007 (χ2 TL = 143,6, p<0,001).
Conclusions: We observed a significantly reduction of E. coli susceptibility for most antibiotics and an increase of E. coli isolates producing ESBLs. Fosfomycin and nitrofurantoin are the best choices for empiric treatment. Prospective studies should be performed in the future to confirm the results of our study.

 
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Rev Esp Quimioter 2010:23(1):43-47

Evaluation of pharmacodynamic target attainment with vancomycin treatment of bacteremia due to Staphylococcus aureus methicillin resistant

J. A. LEPE, M. V. GIL-NAVARRO, M. D. SANTOS-RUBIO, J. BAUTISTA, J. AZNAR

 

Objective: The objective of the study is to evaluate the ability of standard vancomycin dosing strategies actually recommended to attain the pharmacodynamic target of an area under the curve of vancomycin serum concentration versus time from 0 to 24 hours (AUC24h) to minimum inhibitory concentration (MIC) ratio greater than 400:1 for patients with a suspected or documented methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia by individual analysis and Monte Carlo simulation.
Material and methods: The study included all patients admitted with suspected or proven MRSA infection during the years 2007-2008, and who were initially treated with vancomycin at a dose of 30 mg/kg/day, and underwent pharmacokinetic monitoring. The area under the curve of vancomycin serum concentration versus time from 0 to 24 hours (AUC24h) was calculated as daily dose/clearance total (D24h/CL). Additionally, we studied 45 isolates of MRSA obtained from blood cultures in the period 2007-2008. The MIC to vancomycin was determined using Epsilon-test®. The PK-PD parameter calculated was AUC24h/MIC. Microsoft
Excel was used to perform a 10.000 subject Monte Carlo simulation. An AUC24h/MIC ≥ 400 was assumed as the target attainment.
Results: In the individual study, the percentage of patients with AUC24h/MIC50/90 ≥ 400 was 50%. The probability (%) of attaining AUC24h/MIC ratio values ≥ 400 by Monte Carlo simulation was of 66%. The vancomycin MIC value from which the scenario would have to wait a suboptimal treatment (target <90%) was >1 mg/L.
Discussion: This study shows that in the population studied to achieve a vancomycin AUC24h/MIC ≥ 400 is not always attained with the standard dose. Therefore, one would expect a high probability of suboptimal vancomycin AUC24h/MIC ratios for patients infected with organisms with vancomycin MICs of >1 mg/L treated with doses of 30 mg/kg/day.

 
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Rev Esp Quimioter 2010:23(2):63-71

Differences in the use of tigecycline between ICU patients and non-ICU patients

F. ALVÁREZ-LERMA, L. BLANCO, J.A. RODRÍGUEZ, S. GRAU, D. CONDE-ESTÉVEZ, S. LUQUE

 

Background. Tigecycline is a new broad spectrum antibiotic that is predominantly used for the treatment of severe infections both in critically ill patients admitted to the ICU and in non-ICU patients with less severe clinical conditions.
Objetive. To assess differences in the use of tigecycline between ICU patients and non-ICU patients treated with this antibiotics.
Materials and methods. Retrospective, cohort, observational study in which cases were defined as patients who received one or more doses of tigecycline over the first 18 months after approval of the drug in a general hospital. Clinical characteristics, indications, route of administration, clinical response, tolerability and outcome were recorded in the groups of ICU and non-ICU patients. Descriptive data and results of the comparison of both cohorts are presented.
Results. A total of 103 were included in the study, 34 (33%) of which received tigecycline during their stay in the ICU. ICU patients compared to non-ICU patients had a higher SAPS II score on admission (39.0 ± 11.8 vs 26.3 ± 8.0, p < 0.001) and at the time of starting tigecycline treatment (42.2 ± 12.6 vs 25.6 ± 8.2, p < 0.001), were treated with antibiotics for more days (21.4 ± 30.6 vs 13.6 ± 30.5 days, p < 0.012) and received a greater number of antibiotic agents concomitantly (85.3% vs 47.8%,p < 0.001), presented a higher selection of emerging bacterial flora (41.2% vs 15.9%, p = 0.005), particularly Pseudomonas aeruginosa (20.6% vs 2.9%, p = 0.006), higher rate of clinical failure (58.8% vs 21.7%, p < 0.001), longer hospitalization (51.2 ± 39.4 vs 28.7 ± 26.3 days, p < 0.001) and higher overall mortality rate (50% vs 14.5%, p < 0.001) and infection-attributed mortality (20.6% vs 7.2%, p = 0.047).
Conclusions. The patient that receives tigecycline in the ICU has a higher severity level and worse clinical outcome than the non-ICU patient treated with this antibiotic. It is necessary to optimize the indications of tigecycline in the ICU to improve the clinical results.

 
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Rev Esp Quimioter 2010:23(2):53-62

The microbiologist and the catheter related infection

J. GARCÍA-RODRÍGUEZ, M. DE PABLOS, A. GUTIÉRREZ

 

Different multicentre epidemiological studies such as ENVIN-HELICS or EPINE, have remarked that catheter related bloodstream infection (CRBI) is an increasingly condition in hospital environment. The microbiologist plays a major role in the diagnosis, either by recommending what type of catheter must be considered for confirmatory diagnosis, when these samples must be sent for culture, when is indicated to perform surveillance studies of the catheter and what results are clinically significant to be informed. In this paper, differentaspects of the CRBI, such as the pathogenesis, etiology, epidemiology and diagnosis are reviewed. The different microbiological diagnostic methods, both conservatives and those involving the removal of the catheter are up-to-dated.

 
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Rev Esp Quimioter 2010:23(2):72-75

Cefditoren versus ceftazidime in inducer-substrate combinations for the evaluation of AmpC production in a disc approximation test

F. CAFINI, L. AGUILAR, L. ALOU, M. J. GIMÉNEZ, D. SEVILLANO, M. TORRICO, N. GONZÁLEZ, P. CORONEL, J. PRIETO 

 

Objective: To evaluate cefditoren in inducer-substrate combinations to screen for AmpC induction.
Methods: 100 clinical isolates (25 P. aeruginosa, 25 E. cloacae, 14 M. morganii, 13 S. marcescens, 12 C. freundii, 7 P. rettgeri, and 4 E. aerogenes) were tested by the Kirby-Bauer disc approximation method using cefditoren and ceftazidime discs as substrates, and cefditoren and imipenem discs as inducers.
Results: None of the strains showed induction of AmpC with cefditoren-ceftazidime as inducer-substrate combination. Imipenem-cefditoren as inducer-substrate combination was not useful for evaluating strains of P. aeruginosa since no inhibition zones surrounding the cefditoren disc were found. Among evaluable enterobacteria (those showing substrate inhibition zone), inducible Amp C was detected in 48 out of 63 (76.2%) with cefditoren, and in 33 out of 68 (48.5%) isolates with ceftazidime as substrate. Significantly (p= 0.013) higher number of AmpC producers were detected with cefditoren versus ceftazidime (76.2% vs. 48.5%), due to the differences found for E. cloacae (72.8% vs. 21.7%; p= 0.0009) and S. marcescens (100% vs. 54.5%; p= 0.03). Higher mean reductions of diameters around substrate discs were found for cefditoren (4.17 mm) vs. ceftazidime (3.79 mm), reaching statistical significance (p<0.05) for indol-positive proteae: M. morganii (5.32 mm vs. 3.92 mm) and P. rettgeri (3.47 mm vs. 2.64 mm).
Conclusion: Cefditoren showed no induction capability, and when used as substrate (with imipenem as inducer) it offered detection rates of AmpC inducible enterobacteria higher than the imipenem-ceftazidime combination, mainly for Enterobacter spp. and Serratia spp., with higher diameter reductions for indol-positive proteae.

 
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Rev Esp Quimioter 2010:23(2):76-80

Variability in the sensitivity to tigecycline against Acinetobacter baumannii in different culture medium

A. TENORIO-ABREU, J. M. EIROS, E. RODRÍGUEZ-MOLINS, D. ANDALUZ, F. BOBILLO, M. DOMÍNGUEZ-GIL, R. ORTIZ DE LEJARAZU 

 

Introduction. The tigecycline may represent a therapeutic alternative for the control of multiresistant A. baumannii, although there is no consensus regarding the cutoff points for sensitivity or variability of MIC as a function of culture medium used for the antibiogram against this microorganism. Therefore, our objective was to verify this variability, and propose the culture medium that comes closest to the standard method.
Methods. We selected 41 strains of carbapenem-resistant A. baumannii. We analyzed the sensitivity to tigecycline in different culture medium: Mueller Hinton agar Oxoid commercial (C-MH), Mueller Hinton fresh agar BD and Co., USA (F-MH) and ISO-sensitest fresh agar Oxoid, using the E-test and disk. The MICs were compared against those obtained using the technique standard of macrodilution.
Results. The mean MIC and inhibition diameters obtained in the different culture medium corresponded to 9.26 mg/L and 15.1 mm in diameter for MH-C, 1.71 mg/L and 22.7 mm for MH-F; 2.68 mg/L and 20.8 mm for ISO-sensitest. Half the MIC obtained by the standard method of dilution was 0.47 mg/L (SD = 0.21), with values between 0.25 and 1 mg/L.
Conclusion. In the three growth media studied, MICs superior to the standard are observed, which is false to interpret resistance in many cases. However, the medium that comes closer more that of reference is the MH-F.

 
Rev Esp Quimioter 2010:23(2):76-80 [pdf]

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