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

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



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]

Rev Esp Quimioter 2010:23(3):135-143

Impact factor and quality of scientific publications on Microbiology: the example of the Spanish Journal of Chemotherapy 



Introduction. The impact factor of a journal is the quantitative analysis of the number of citations obtained during a specific period of time. This currently is the standard tool to measure the quality of the publication and a way to evaluate the research trajectory of a scientist.
Methods. Search for bibliometric indicators: Journal Citation Reports, SCImago Journal Rank and Potencial Impact Factor for the Spanish Medical Journals of the Instituto de Historia de la Ciencia y Documentación López Piñero (IHCD). To identify criteria of editorial quality, of visibility and of spreading by reviewing databases such as the Online Regional Information System for Scholarly Journals from Latin America, the Caribbean, Spain and Portugal (LATINDEX), SciELO (Scientific Electronic Library Online), DIALNET and the Collective Periodical Publications Catalogue of Spanish Healthcare Science Libraries, known as C17.
Results. For the first time, the Spanish Journal of Chemotherapy appears in the 2009 edition of JCR, previously by joined the two spanish journals Clinical Microbiology and Infectious Diseases and International Microbiology, both ranked at a lower position. While calculating factors of national and international impact of the five publications included in the category of Pharmacology and Pharmacy as part of theproject initiated by the IHCD, the Spanish Journal of Chemotherapy showed the best results.
Conclusions.The Spanish Journal of Chemotherapy obtained good results in analysed bibliometric indicators, positioning it at the top of the ranking of Spanish medical journals. A good spreading helped to maintain visibility on the publication in the editorial field.   

Rev Esp Quimioter 2010:23(3):135-143 [pdf]

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



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.

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

Rev Esp Quimioter 2010:23(3):144-152

Comparative activity of doripenem, meropenem, and imipenem in recent clinical isolates obtained during the COMPACT-Spain epidemiological surveillance study 



Introduction. Doripenem is a new carbapenem with broad spectrum antibacterial activity indicated for the treatment of nosocomial pneumonia and complicated urinary and intraabdominal infections.
Methods. Isolates of Pseudomonas aeruginosa, Acinetobacter and Enterobacteriaceae from patients with nosocomial pneumonia, bacteremia and complicated intraabdominal infections attended in 16 Spanish hospitals were included (October 2008–May 2009). Susceptibility to imipenem, meropenem and doripenem was studied with the Etest method, and the results were interpreted according to the EUCAST criteria.
Results. Considering all the isolates, doripenem (MIC50 0.12 mg/L) was 2- to 8-fold more active than meropenem (0.25 mg/L) and imipenem (1 mg/L). In relation to Enterobacteriaceae, the MIC50 and MIC90 values of doripenem and meropenem were similar (0.03 and 0.12 mg/L, respectively) and clearly superior to those of imipenem (0.25 and 1 mg/L). In the case of P. aeruginosa, MIC50 and MIC90 were more favorable to doripenem (0.25 and 16 mg/L) than to meropenem (0.5 and ≥64 mg/L) or imipenem (2 and ≥64 mg/L). In this species, the percentage of strains with lower MIC values for doripenem among those exhibiting intermediate susceptibility and resistance to meropenem was 63.0% (29/46) and 61.7% (63/102), respectively, versus only 4.3% (2/46) and 1.9% (2/102) with higher MIC values for doripenem.
Conclusions.The results obtained in this study are similar to those reported in other countries, and reinforce the superior in vitro activity of doripenem versus the other carbapenems and its position in the treatment guidelines regarding the nosocomial infections for which it is indicated.   

Rev Esp Quimioter 2010:23(3):144-152 [pdf]

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)



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.

Rev Esp Quimioter 2010:23(1):36-42 [pdf]

Rev Esp Quimioter 2010:23(4):158-168

Nosocomial candidemia: new challenges of an emergent problem 



Candida spp. are currently one of the most common causes of bloodstream infections in hospitals. Over the last two decades there has been a shift towards a greater involvement of non-Candida albicans as the cause of candidemia. Several of these non-albicans spp. (e.g., C. glabrata and C.krusei) exhibit resistance to traditional triazole antifungals (fluconazole), and cross-resistance with newer triazoles (voriconazole), focusing attention on the first-line use of antifungals such as the echinocandins, which possess improved activity against fluconazole-resistant strains. Early and adequate empirical treatment as well as early removing of the central catheters are the main factors related to mortality; thus it is necessary to implement guidelines of empirical treatment (including these aspects) in patients with risk factors and possible candidemia. Recent treatment guidelines from the Infectious Diseases Society of America (IDSA) recommend an echinocandin as primary therapy for non neutropenic or neutropenic patients with moderately severe to severe candidiasis and for patients at risk for infection with a triazole-resistant strain; the increasing MIC of echinocandins in case of C. parapsilosisis also an emerging concern. Clinicians should remain vigilant to prescribe early empiric treatment of patients at risk of having candidemia.   

Rev Esp Quimioter 2010:23(4):158-168 [pdf]

Rev Esp Quimioter 2010:23(1):43-47

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



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.

Rev Esp Quimioter 2010:23(1):43-47 [pdf]

Rev Esp Quimioter 2010:23(4):169-176

Antifungal agents in the treatment of systemic infections: Relevance of mechanism of action, activity profile and resistances 



The availability of different therapeutic alternatives has modified the treatment of systemic fungal infections. There commendations of antifungal therapy vary according to species which causes the mycosis and its susceptibility. Consequently, the knowledge of action mechanism, activity profile and resistances to antifungal agents are essential for the clinical practice. Amphotericin B is the antifungal agent exhibiting the broadest spectrum of activity, it is a fungicidal drug and resistances have been hardly ever described. The triazoles compounds also have a broad spectrum, but their massive use for some therapeutic indications has led to emergence of strains and species of yeasts with resistance to fluconazole and of filamentous fungi itraconazole resistant.The echinocandins exhibit fungicidal effects for yeasts andafungistatic activity against moulds, and secondary resistance to these agents is uncommon.   

Rev Esp Quimioter 2010:23(4):169-176 [pdf]

Rev Esp Quimioter 2010:23(2):63-71

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



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.

Rev Esp Quimioter 2010:23(2):63-71 [pdf]

Rev Esp Quimioter 2010:23(4):177-183

Prophylaxis and treatment of invasive fungal infection in neutropenic patients 



Prophylaxis and treatment constitute the basis for reducing the mortality due to IFI. Prophylaxis is currently the standard practice in most hospitals and is recommended by the principal guidelines. Fluconazole has proved to be useful to prevent and reduce the mortality due to yeast IFI in several contexts. Although its use has led to the emergence of some resistant strains of Candida, it has not been a generalized problem and the number of lives saved has been worth it. But its major disadvantage is the lack of impact on IFI by molds. So, in patients at high risk for IFI due to filamentous fungi, it is necessary the employ of extended spectrum drugs. For the empirical and preemptive approach, it is necessary to have in mind which fungi have to be covered and  the spectrum of the available antifungal agents. For the treatment of established infection by Candida spp., before the identification of species, we must consider different host (like the use or not of prophylactic fluconazole) and clinical factors (like the evidence or not of diseminated infection or severe sepsis). Primary combination of antifungal agents for the treatment of invasive aspergillosis has to be considered in cases of central nervous system disease, respiratory failure, serious sepsis,  and extensive or cavitated pulmonary lesions.    

Rev Esp Quimioter 2010:23(4):177-183 [pdf]