Rev Esp Quimioter 2008;21(3):149-152

β-lactam susceptibility of Escherichia coli isolates from urinary tract infections exhibiting different resistance phenotypes

 

M. Lerma ,  L. Cebrián ,  M. J. Giménez ,  P. Coronel ,  M. Gimeno ,  L. Aguilar ,  J. García de Lomas 

Susceptibility to β-lactams was determined in 203 recent Spanish E. coli isolates from urinary tract infections exhibiting different resistance phenotypes: a) susceptible (n = 60); b) quinolone-resistant (n = 45); c) penicillinase (n=64); d) hyperproduction of penicillinase (n=8); e) inhibitor resistant TEM (IRT) (n=18), and f) extended spectrum betalactamase (ESBL) (n=8). Minimum inhibitory concentration (MIC) determination by agar dilution and susceptibility tests for ESBL detection by macrodilution were performed following CLSI recommendations. All the β-lactams tested showed high activity against susceptible and penicillinase phenotypes, with close to 100 % susceptibility. Hyperproduction of penicillinase increased MIC90 values for all antibiotics except for meropenem, with 100% resistance to cefuroxime and amoxicillin/clavulanic acid, and 100% susceptibility to cefotaxime, piperacillin/tazobactam and meropenem. All the antibiotics, except for amoxicillin/clavulanic acid, exhibited high activity against IRT. Meropenem, cefminox and piperacillin/tazobactam exhibited the highest activity against ESBL, followed by amoxicillin/clavulanic acid. The most active compound among the parenteral antibiotics was meropenem, regardless of the resistance phenotype. Among the oral antibiotics, the most active compound was cefditoren with the exception of ESBL where amoxicillin/clavulanic acid where the MIC90 value was one dilution lower.  

Key words: E. coli. β-lactamase. Cefditoren.

Rev Esp Quimioter 2008;21(3):149-152  [pdf] 

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Rev Esp Quimioter 2008;21(3):143-148

Obtain best usage of meropenem dose in severe infections. Results of an observational multicenter study

B. Álvarez-Sánchez ,  F. Álvarez-Lerma ,  J. L. Romero ,  L. Fernández Quero ,  F. Ruiz Ferrón ,  H. Sancho Ruiz   

Objective. To describe the effectiveness and tolerability of the dose adjustment of meropenem in empirical treatment of nosocomial infections in critically-ill patients admitted to intensive care medicine services.

Methods. Prospective, observational and multicenter study in patients admitted to 17 intensive care medicine services with nosocomial infection, who were initially treated with meropenem, 1 g every 8 h, were eligible. The initial dose was adjusted to 0.5 g every 8 h if there were: a) a favorable clinical course, and b) microbiological isolation of meropenem-susceptible pathogens or absence of pathogens in cultures.

Results. Ninety-two patients in whom meropenem doses were adjusted to 0.5 g every 8 h were included. Ventilator-associated pneumonia followed by bacteremia was the most frequently treated infections. Microbiological studies were positive in 53 patients, with a predominance of gram-positive bacteria (53.7%), especially methicillin-susceptible Staphylococcus aureus, followed by gram-negative bacteria (42.7 %). A total of 18 patients were not evaluable at the end of treatment. Sixty-seven (90.5 %) of the 74 evaluable patients had a favorable clinical course (54 patients cured and 13 improved). In 50 out of 53 microbiologically evaluable cases, eradication or apparent eradication of initial microorganisms was achieved. In 3 cases, the initial pathogen persisted: Acinetobacter baumannii (2 cases) and Pseudomonas aeruginosa (1 case). On three occasions, new pathogens developed during treatment: A. baumannii (2 cases) and methicillin-resistant S. aureus (1 case). Adverse events occurred in 3 patients (4%), none of which was considered severe, and withdrawal of meropenem was not necessary. A total of 25 (27.2 %) patients died, three of them in relation to the infectious process.

Conclusions. Dose adjustment of meropenem to 0.5 g every 8 h is a useful tool in the treatment of severe nosocomial infections in patients admitted to services of intensive care medicine except in cases in which causative pathogens are non-fermenting Gram-negative bacteria.  Key words:Meropenem. Severe infections. Therapeutic strategy. Acinetobacter baumannii. Pseudomonas aeruginosa.  

Rev Esp Quimioter 2008;21(3):143-148 [pdf]

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Rev Esp Quimioter 2008;21(2):127-142

Recommendations of antifungal treatment in patients with low grade inmunosuppression

 

J. Barberán ,  J. Mensa ,  C. Fariñas ,  P. Llinares ,  R. Serrano ,  R. Menéndez ,  C. Agustí ,  M. Gobernado ,  J. R. Azanza ,  J. A. García Rodríguez 

Because of the relevance that the systemic mycoses has acquired in non-highly immunocompromised patients, thetreatment difficulties they have due to the increase of the non-albicans Candida species and the need to have a better and more rational use of the new antifungal agents (voriconazole, posaconazole, caspofungin, anidulafungin and micafungin), an experts’ panel on infectious diseases in representation of the Spanish Society of Chemotherapy, Spanish Society of Internal Medicine, and Spanish Society of Pneumology and Thoracic Surgery has met in order to make a few recommendations based on the scientific evidence in an effort to improve their efficiency.

  

Key words:Systemic mycoses. Low grade immunosuppression. New antifungal agents.

Rev Esp Quimioter 2008;21(2):127-142 [pdf]

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Rev Esp Quimioter 2008;21(2):123-126

Isolation of the first metallo-β-lactamase producing Klebsiella pneumoniae in Lebanon

 

Z. Daoud ,  E. Hobeika ,  A. Choucair ,  R. Rohban 

  

Introduction. A 58 year-old man was admitted to the Saint Joseph Hospital-Raymond and Aida Najjar polyclinic in Beirut on July 17, 2007 to undergo surgery for a moderately differentiated colonic adenocarcinoma (T3N0). Following several discharges and re-admissions, an extended spectrum beta-lactamase (ESBL) producing Escherichia coli susceptible to imipenem was isolated. The patient was put on imipenem and metronidazole. Three weeks later, imipenem (IMP) resistant Klebsiella pneumoniae was isolated.

Methods and results. The antimicrobial susceptibility profile of the imipenem-resistant Klebsiella pneumoniae strain and related minimum inhibitory concentrations of antibiotics were determined. Hydrolysis of IMP was evaluated and production of metallo-β-lactamase (MBL) was detected by a double disk-synergy test, ethylene diamine tetraacetic

acid (EDTA) inhibited the imipenemase activity, whereas clavulanate and tazobactam did not, this suggesting the production of a metallo-β-lactamase. Isoelectric focusing analysis was performed and indicated the presence of a cefotaximase (blaCTX-M-15). Polymerase chain reaction (PCR) was used and detected the presence of blaIMP-1 and blaCTX-M genes.

Conclusions. During the last decade, many hospital outbreaks caused by ESBL-producing Enterobacteriaceae spp. have been reported in Lebanon. To our knowledge, this is the first report of a clinical isolate of K. pneumoniae producingan MBL in Lebanon.   

 

Key words: Metallo-β-lactamase. Klebsiella pneumoniae. Extended spectrum beta-lactamase (ESBL). Resistance. Carbapenemases. BlaIMP-1. BlaCTX-M-15. Lebanon.

Rev Esp Quimioter 2008;21(2):123-126 [pdf]

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Rev Esp Quimioter 2008;21(2):115-122

Clinical relevance of bacterial resistance: an historical approach (1982-2007)

 

J. Gómez ,  E. García Vázquez ,  J. Ruiz Gómez 

Bacterial resistance is currently one of the most important problems of infectious pathology. The relation between in vitro and in vivo bacterial resistance is not always well defined because therapeutic failure is also related to other factors (pharmacokinetics and pharmacodynamics). In addition, there are disagreements between the in vitro and in vivo activity of several antimicrobials (especially ciprofloxacin) due to their low bactericidal activity. In infections due to ciprofloxacin susceptible S. pyogenes, S. aureus, S. epidermidis, E. faecalis, E. coli producing extended spectrum beta-lactamase (ESBL), K. pneumoniae and E. cloacae their clinical use is not associated to cure because of the development of resistances that are induced during the antibiotic treatment. Ceftazidime in infections due to susceptible strains of K. pneumoniae and E. cloacae and ceftriaxone in infections due to methicillin susceptible S. aureus also do not have a good correlation between in vitro and in vivo results due to their low bactericidal activity and to the development of resistances during treatment. The main clinical impact of resistant bacteria is related to the failure of empirical treatments, which is associated to a higher mortality, especially in severe infections with methicillin-resistant S. aureus, Enterobacteriae ESBL and multiresistant P. aeruginosa and A. baumannii. One of the main risk factors for the development of bacterial resistances is the increase of the consumption of several antibiotics. The development of protocols agreed upon by consensus may decrease the impact of bacterial resistances. The knowledge of the previous use of antibiotics is an especially relevant issue to suspect that an infection might be due to resistant bacteria. Resistant pathogens are a severe problem in the clinical setting and the question is of such a complexity that it requires a multidisciplinary effort that involves the different professionals of the Internal Medicine-Infectious Diseases, Microbiology, Pharmacology, Pharmacy and Preventive Medicine Departments and hospital directors and that results in unified and protocolized actions regarding the clinical and therapeutical approach for the management of severely infected patients.    

Key words:Resistance. Extended spectrum beta-lactamase (ESBL). Antibiotics. Protocols. Infection.

Rev Esp Quimioter 2008;21(2):115-122 [pdf]

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Rev Esp Quimioter 2008;21(2):99-114

Anidulafungin

 

M. Gobernado ,  E. Cantón 

  

Anidulafungin is a new echinocandin antifungal agentrecently approved in Spain by the Spanish Drug Agency. As other echinocandins, it inhibits a selective target, 1,3-β-D-glucan synthesis, a major structural component of the fungal cell wall which is not present in mammalian cells, this avoiding toxicity problems. It has fungicidal activity against many Candida spp., including fluconazole-resistant, and fungistatic activity against other yeast and moulds such as Aspergillus spp. Clinical trials have shown non-inferiority of anidulafungin to fluconazole for invasive, including candidemia, and non-invasive Candida infections. It is well-tolerated, and no drug-related serious adverse events have been reported. Anidulafungin, which has a very long half life, is slowly degraded by human peptidases and proteases and has a low drug-drug interaction profile based on its lack of interaction with the cytochrome P450 system. Thus, dosing adjustments of anidulafungin based on age, gender, body weight, disease status, concomitant therapy or renal or hepatic insufficiency is not necessary. As it does not interact with amphotericin B and voriconazole, cyclosporine, tacrolimus and other drugs, it can be used in combination with other antifungal agents and co-administered with immunosuppressant drugs. It is generally well-tolerated in clinical trials. Its most frequent adverse events are nausea, vomiting, moderate diarrhea, transient elevation of hepatic enzymes and headache. Some of the patients have mild, passing reactions such as facial blushing, nausia and dyspnia related with rapid intravenous perfusion. Its antifungal activity, clinical efficacy, safety profile, and pharmacokinetic characteristics make it a suitable alternative antifungal compound for therapy of mucosal candidiasis, candidemia and invasive candidiasis, above all in patients with some degree of renal and hepatic insufficiency.

  

Key words: Anidulafungin. Candida spp. Aspergillus spp.

Rev Esp Quimioter 2008;21(2):99-114  [pdf]

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Rev Esp Quimioter 2008;21(2):93-98

Methicillin-resistant Staphylococcus aureus bacteremia. Predictor factors for an isolate with a vancomycin minimal inhibitory concentration ≥2 mg/l

 

M. Ortega ,  F. Marco ,  A. Soriano ,  M. Almela ,  J. A. Martínez ,  A. Muñoz ,  J. Mensa 

A greater rate of treatment failures with vancomycin in methicillin-resistant Staphylococcus aureus (MRSA) bacteremia has been reported recently when the minimum inhibitory concentration (MIC) is ≥ 2 mg/l. This study has aimed to evaluate if there are clinical and/or epidemiological factors that predict isolation of a MRSA strain with MIC of vancomycin of ≥2 mg/L in the bacteremia episodes collected during a 15 year period (January 1991 to December 2005) in a tertiary urban hospital. During the study period, a total of 478 episodes of MRSA bacteremia were studied prospectively. The following clinical variables were recorded for each one: age, gender, comorbidity, previous administration of vancomycin or another antibiotic, prognosis of baseline diseases, bacteremia focus, shock, empiric antibiotic received and mortality. The MIC of vancomycin of 419 strains (88%) was determined with the E-test. In 216 (52%) of the isolations the MIC of vancomycin was 1.50 mg/L, in 110 (26%) of the cases it was ≤1 mg/l and in 93 (22%) 2 mg/l. Uni-and multivariate analyses were made, comparing the clinical variables of the patients infected by strains with MIC of vancomycin ≥2 mg/l regarding the MIC strains ≤1 mg/l. In the last 3 years of the study (2003-2005) the proportion of the strains with MIC of vancomycin ≥ 2 mg/l was significantly greater than those isolated with MIC ≤ 1 mg/L (44 % vs 3 %; p<0.001). In the multivariate analysis, the only clinical characteristic associated independently to the isolation of a strain with MIC ≥2 mg/l was the nosocomial-acquired infection OR (95 % CI):1.94 (1.04-3.63); p=0.04. Although the isolation of a MRSA strain with MIC of vancomycin ≥2 mg/l is more frequent in the nosocomial-acquired bacteremia episodes, in the clinical practice, it is not a useful predictive parameter because the frequency of isolation of these strains in the community is also high.    

 

Key words: Methicillin-resistant S. aureus bacteremia. Decrease sensitivity to vancomycin.Predictive factors. Empiric treatment of methicillin-resistant S. aureus bacteremia. 

Rev Esp Quimioter 2008;21(2):93-98 [pdf]

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Rev Esp Quimioter 2008;21(2):83-92

Levofloxacin in the treatment of nosocomial infection in critically ill patients

 

F. Álvarez Lerma ,  J. L. Romero Luján ,  A. Morón Jiménez ,  R. Ortiz López ,  M. Borges Sá ,  S. Grau Cerrato ,  M. P. Gracia Arnillas

 

Introduction. Levofloxacin (LVX) is one of the most frequently used antibiotics in critical patients admitted to Spanish Intensive Care Units (ICU). Their use in community acquired infections has been widely documented, while it is less frequent and known in nosocomial infections (NI).

Objective. To describe the indications and utilization patterns of LVX in the treatment of NI in patients admitted to Spanish ICU.

Material and methods. Open-label, retrospective, observational and multicenter study. All patients admitted to ICU and who were being treated for NI with LVX in the years 2004-2005 were included. A case report form (CRF) was drawn up and included demographic, infection, treatment, infectious process and patient development variables. NI-dependent LVX usage was described.A logistical regression analysis was carried out in order to identify the variables associated with a satisfactory response. Results are expressed by means of the odds ratio and a 95% confidence interval.

Results. A total of 949 patients who were given LVX for the treatment of 1,103 NI were recruited in 87 ICU:460 (41.7%) with non-mechanical ventilation associated pneumonia, 256 (23.2 %) mechanical-ventilation associated pneumonia, 107 (9.7 %) with primary or vascular catheter-related bacteremia, 47 (4.3 %) with urethral catheter-related urinary infections, 42 (3.8%) with organspace or deep surgical infections and 191 (17.3%) who had other types of infection. An APACHE II upon admission of 19.6 (SD: 8) and severe sepsis or septic shock systemic response in 50.4% of all cases. On 776 (82.7%) occasions treatment was initiated on an empirical basis and in 589 (62.1%) cases the dose of choice was of 0.5 g/12 h, with a mean duration of 9 days. In 738 (77.8 %) patients, LVX was used in association with other antibiotics. The clinical response by treatment end was rated as satisfactory in 67.4 % of all NI. Factors related to a non-satisfactory response were as follows: APACHE II(OR: 1.05; 95% CI: 1.028-1.078); septic shock (OR: 2.62;95 % CI: 1.623-4.219); the requirement for changes intreatment due to poor clinical progress (OR: 66.67; 95% CI: 15.384-250), the presence of non-covered microorganisms (OR: 6.58; 95% CI: 3.663-11.765), the appearance of new resistant pathogens (OR: 6.94; 95 % CI: 2.445-19.608) or the diagnosis of a new infection (OR: 3.68;95% CI: 1.504-8.929); solid neoplasm (OR: 1.98; 95% CI:1.156-3.899); chronic liver disease (OR: 3.11; 95 % CI:1.429-8.475) and the absence of etiology confirmation (OR: 2.39; 95 % CI: 1.624-3.510). One or more adverse events which were possibly or probably related to the use of LVX were detected in 104 (11.0%) patients. Totalintra-ICU mortality amounted to 26.1%, while the accumulated in-hospital mortality was 33.8%.

Conclusions. LVX is a common therapeutic option in the treatment of nosocomial infections in critical patients.It is predominantly used in an empirical manner, at a dose of 0.5 g every 12 hours and in combination with other antibiotics.

Key words: Levofloxacin. Nosocomial infections. Critical patients. ICU.

Rev Esp Quimioter 2008;21(2):83-92 [pdf]

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Rev Esp Quimioter 2008;21(1):60-82

Recommendations of antimicrobial treatment in patients allergic to beta-lactam antibiotics

 

J. Barberán ,  J. Mensa ,  C. Fariñas ,  P. Llinares ,  P. Olaechea ,  M. Palomar ,  M. J. Torres ,  E. Moreno ,  R. Serrano ,  J. A. García Rodríguez 

  

Beta-lactam antibiotics are the cornerstone of most of the severe bacterial infections. However, their use can be limited by resistances and allergic reactions. Allergic reactions to â-lactam antibiotics account for only a small proportion of reported adverse drug reactions, but they are related with an important morbidity, mortality and increase of the health care costs. Drug-specific IgE antibodies cause early reactions, whereas T cells play a predominant role in delayed hypersensitivity reactions. For penicillin a major antigenic determinant and several minor determinants have been identified. Clinical assessment is mandatory by medical history, skin and other testing, including provocation. If the â-lactam should be avoided or a desensitization procedure should be performed depends on the nature and severity of the reaction. Several new antibiotics are currently available (tigecycline, linezolid, daptomycin, etc.) that are as effective and safe as â-lactams. In this article we have developed a few recommendations for the management of patients with allergy to â-lactams on the basis of evidence and expert opinion.

  

Key words:Allergy. beta-lactam. New antibiotics.

Rev Esp Quimioter 2008;21(1):60-82 [pdf] 

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Rev Esp Quimioter 2008;21(1):45-59

Diagnosis and treatment of acute rhinosinusitis: second consensus

 

M. Tomás Barberán ,  P. Ortega del Álamo ,  J. Mensa Pueyo ,  J. A. García Rodríguez ,  J. Barberán 

  

The publication of different studies, articles and documents over recent years greatly justifies the revision of the year 2003 Consensus on the diagnosis and treatment of rhinosinusitis made jointly by the Spanish Society of Chemotherapy and the Spanish Society of Otolaryngology and Cervical Facial Pathology. The most significant features to be analyzed consider a new classification, the accumulated evidence on the role of first line of nasal corticosteroids, the demonstration of the utility of different antimicrobial agents with wide clinical experiences and the appearance of clinical studies with new antimicrobial agents that support their utility. Due to its evolution, rhinosinusitis is considered to be acute (viral or non-viral origin) if it lasts less than 12 weeks, chronic when it exceeds this time period and recurrent acute when three or more acute episodes are suffered in one year. Based on its severity, rhinosinusitis can be classified as mild, moderate or severe. Rhinosinusitis may present without or with complications. Rhinosinusitis symptoms resolve spontaneously in 40% of the patients. However, medical treatment is indicated to provide symptomatic relief, accelerate the resolution of the clinical picture, prevent possible complications and avoid evolution to chronicity. Antimicrobial agents and topical nasal corticosteroids (used alone or in combination with antimicrobial agents) are the treatments that have demonstrated therapeutical utility in rigorous and controlled clinical trials. In mild acute maxillary rhinosinusitis without previous antibiotic treatment, the treatment of choice is amoxicillin/clavulanate or cefditoren, while when it is moderate or mild in patients previously treated with antibiotics, levofloxacin or moxifloxacin are preferable, the amoxicillin/clavulanate or cefditoren drugs remaining as good alternatives. In the severe forms, third generation cephalosporins, such as cefotaxime or ceftriaxone, are indicated and amoxicillin/clavulanate or ertapenem are good options in the non-polypoidal chronic forms.

  

Key words:Rhinosinusitis. Antimicrobial agents. Nasal corticosteroids. Consensus.

Rev Esp Quimioter 2008;21(1):45-59 [pdf]  

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