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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Rev Esp Quimioter 2008;21(1):37-44

Improvement of bactericide activity in hospital treatment of gram positive infections

 

L. Aguilar ,  J. Barberán ,  J. Prieto ,  M. J. Giménez 

  

Vancomycin is currently the standard treatment of gram-positive bacteria inducted nosocomial infections. However its bactericidal activity may be affected by different factors related to its antibacterial activity, pharmacokinetic properties or the infecting bacteria. Based on these facts, this article reviews the clinical importance that bactericidal activity has against susceptible bacteria and the compromise of this activity due to inadequate pharmacodynamic parameter values. From the bacterial target perspective, the clinical importance of the compromised bactericidal activity due to the decreased susceptibility, tolerance, heteroresistance and resistance is reviewed. In addition the characteristics of an antimicrobial targeted for gram positive nosocomial infections as well as the degree of adhesion to them of the bactericidal antibiotic daptomycin are described.

  

Key words:Vancomycin. Daptomycin. Bactericidal activity. Heterorresistance. Tolerance. 

  

Rev Esp Quimioter 2008;21(1):37-44 [pdf]  

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Rev Esp Quimioter 2008;21(1):32-36

Analysis of decrease in sensitivity in influenza A (H5N1) avian and human strains to neuraminidase inhibitors

 

J. Reina 

The options for efficient control of avian influenza A (H5N1) viruses include specific vaccination and antiviral prophylaxis and treatment. However, because H5N1 viruses undergo continuous antigen mutations, the production of a matched vaccine strain is currently not possible. Thus, during the early pandemic period, specific control measures would rely solely on antiviral drugs. Now only neuraminidase inhibitors (NIs) (zanamivir and oseltamivir) are considered for prophylaxis and therapy in patients with H5N1 infection. The sensitivies of H5N1 strains to the NIs fell into 3 groups. The clade I viruses isolated before 2004 were as sensitive to NIs than reference strains (first group). But the clade I viruses isolated from 2004 were 6 to 7-fold less sensitivity to NIs (second group). The clade II strains isolated from 2005 to 2007 demonstrated a 15 to 30 fold decrease in sensitivity to oseltamivir compared with clade I viruses (third group). The specific decrease in sensitivity to oseltamivir of both Cambodian and Indonesian clade 2 influenza H5N1 isolates is disturbing, especially because they maintain their pathogenicity and transmissibility in birds and are clearly pathogenic in humans. No altered sensitivity to zanamivir has been detected. Zanamivir may also play an important role in pandemic stockpiles. Because the clade 2 virus is now spread through parts of Europe and Africa, continued global collaboration and phenotypic testing of NIs sensitivity are critical for a future pandemic. 

 

 

Key words:Avian influenza. H5N1. Neuraminidase inhibitors. Antiviral resistance.

Rev Esp Quimioter 2008;21(1):32-36 [pdf]

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Rev Esp Quimioter 2008;21(1):26-31

Antimicrobial selection criteria evaluation by family doctors and general practitioners

M. A. Ripoll ,  A. Orero ,  D. Vicente ,  A. Navarro ,  J. Gónzález ,  J. Prieto 

 

Objective. This study has aimed to know the criteria used by the Spanish medical practitioners/family doctors (MP/FD) when choosing an antimicrobial agent in their daily practice and to compare it with that existing one decade ago.

 

Material and methods. This is an observational, cross-sectional study performed with a structured personal interview to 450 MP/FDs randomly chosen with representativeness on the national level. The field work was made by specialized personnel in the last quarter of the year 2006. A 95.5% confidence interval margin was proposed, with a sample error = 4.7%, for maximum dispersion response (p=q=50).

 

Results. The parameter considered most when choosing an antibiotic treatment (spontaneous response) is clinical efficacy (two out of every three doctors). Clinical efficacy is following by the dosage regime and tolerability/safety, which was the principal parameter expressed ten years ago. Following these are antibacterial spectrum, administration route, price and bacterial resistances. However, they considered that the latter significantly influence clinical efficacy and when they are not relativized with other parameters, the doctors state that they take them into account «much/a lot». It seems that the opinion of the patient is usually considered and that the protocol, scientific information and expert’s opinions are the principal sources of information considered when prescribing an antimicrobial agent. Amoxicillin/clavulanate is the antibiotic drug of choice in all upper and lower respiratory tract infections. There is overestimation of the bacterial etiology in throat infections and acute bronchitis and S. pyogenes to betalactamic antibiotics. It is concluded that knowledge of the Spanish MP/DF regarding antimicrobial therapy has improved in recent years and that clinical efficacy, related with bacterial eradication and not only with clinical remission, is the factor that should be considered when choosing an antibiotic.

 

Key words:Antimicrobial therapy. Utilization of antibiotics. Antibiotic selection criteria. Antibiotics. Primary health care.

Rev Esp Quimioter 2008;21(1):26-31 [pdf]  

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Rev Esp Quimioter 2008;21(1):22-25

Situation of Mycobacterium tuberculosis drug resistances in Spain

 

M. S. Jiménez ,  M. Casal ,   (GEM) 

  

Introduction. The Mycobacteriology Spanish Working Group (MSWG) has conducted an epidemiological, descriptive and retrospective study to try to know the level of first line drug resistances in Mycobacterium tuberculosis strains in Spain.

 

Material and methods. Data were obtained from a total of 1083 strains isolated between October and November 2006 in 120 microbiology laboratories from 16 autonomous communities and Melilla.

  

Results. A primary resistance rate of 8.3% and 4.9% was obtained for isoniazid (INH). The probability of suffering resistant tuberculosis was major in the immigrant population with a resistance rate of 12%. Repeating these surveillance studies in later years is recommended.

Key words: Tuberculosis. Resistance. Antituberculous agents.

Rev Esp Quimioter 2008;21(1):22-25 [pdf]  

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