Microbial Resistance Towards Antibiotics: Still A Critical Issue

Main Category: MRSA / Drug Resistance
Article Date: 21 Apr 2008 - 4:00 PDT

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ECCMID Opening Press Conference. "The problem of antibiotic resistance continues to grow and this is mainly a consequence of longstanding misuse and abuse of antimicrobial agents", said Prof. Fernando Baquero, Congress President (Hospital Ramón y Cajal, Madrid). Among all the pathogens, methicillin-resistant Staphylococcus aureus (MRSA) is a frequent culprit in infections (mainly respiratory, urinary or skin infections) in hospital settings and nursing homes. Despite this, the general public is unfamiliar with this threat (F. Verhoeven et al. - ECCMID abstract no.1387) and unaware that MRSA can contaminate not only patients' rooms and healthcare workers, but also the environment outside hospitals, including houses or workplaces.

"Bacterial resistance to antibiotics commonly used in children is already a critical problem because we cannot use all the antibiotics commonly available for use in adults for the treatment of children", pointed out Prof. Baquero. Clinicians are particularly concerned about the emergence of hyper-virulent and hyper-resistant strains of Pneumococcus (the pathogen more frequently responsible for ear infections among children), whose epidemiology and interactions with hosts have changed rapidly during recent years. "The relentless rise of resistant bacterial strains will be a critical issue for many years to come as innovative antibiotics are not likely to be developed and marketed, and industrial research facilities on antimicrobial agents are being increasingly shut down" - said Prof. Baquero. "We need to change our attitude towards the clinical use of existing antibiotics, as this has been the main factor in the emergence of resistant organisms". A recent study which analysed all the outpatients oral antibiotic prescriptions in Canada (F. Marra, S. Mak et al. ECCMID abstract no.254 ) seems to reveal a link between antibiotic use and socioeconomic determinants: "this is the proof that variables other than clinical appropriateness are now playing an unacceptable role in antibiotic prescription", concluded Prof. Baquero.

The risk of colonization by antibiotic resistant bacteria (ARB) is higher in hospitalized patients and varies greatly during exposure to different antibiotics, being mainly related to the underlying conditions and length of hospitalisation (E. Tacconelli, G. De Angelis, R. Cauda et al. - ECCMID abstract no.1789). Therefore, "periodic screening of high risk patients consuming antibiotics should be strongly encouraged". In recent years an increasing incidence of antibiotic resistant bacteria in hospital settings has been reported, rising to 7 cases per 1,000 hospital admissions. A study aimed to analyse risk factors for ARB infections - mainly due to methicillin-resistant Staphylococcus aureus (MRSA), or extended-spectrum beta-lactamase (ESBL)-producing bacteria, and multi-drug-resistant (MDR)-gram negative bacteria (resistance to >3 commonly used antibiotics) - has revealed an increased risk of ARB colonization in patients aged >60 years with urinary catheters and clinical signs of bacterial infections at hospital admission, in subjects previously treated with antibiotics, and in those with severe underlying conditions (E. Tacconelli, G. Fadda, R. Cauda et al. ECCMID abstract no.1823). "Recognition of these risk factors may influence the selection of empirical treatments", said Prof. Baquero.

Other than MRSA contamination, infections caused by gram negative bacteria are of particular concern. The most commonly isolated gram-negative bacteria from both community acquired and nosocomial blood stream infections are Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Legionella pneumophila, being these latter pathogens responsible for serious or even life-threatening pneumonia. "One of the problems in dealing with these bacteria" - said Prof. Baquero - "is that we must routinely wait for the results of subcultures, which are not available until the following day".

"Therefore, patients must immediately receive broad spectrum antibiotics and continue this empiric therapy for several days (once started), before a specific treatment can be instituted". "There is an absolute need to control the microorganism during the first hours in cases of severe infection, by using the safest antibiotics. In terms of patient safety, the clinical management during the first few hours of admission is of critical importance: we cannot fail there!", said Prof. Baquero. "This can lead to overuse of inappropriate antimicrobial agents". A study conducted by H. Chang and colleagues (ECCMID abstract no.1150) has concluded that higher consumption of certain antibiotics is significantly correlated with increasing rates of antibiotic-resistant E.coli and K. pneumoniae. "Increases in the prevalence of antibiotic-resistant gram-negative bacilli in hospital settings seem to be frequently related to the high selective pressure of antibiotics, thus reinforcing the need for continuous surveillance of antibiotic use, with the aim of encouraging appropriate prescription of antimicrobials and reduction of antibiotic resistance", concluded Prof. Baquero.

Among gram negative microorganisms, Pseudomonas aeruginosa is an opportunistic human pathogen - characterized by enhanced antibiotic resistance - which accounts for 11% of nosocomial infections worldwide. This bacterium is known to cause life-threatening infections, especially in immunocompromised subjects and patients with cystic fibrosis. A Spanish study (M. Salvadó, J. Garau, P. Almagro et al. - ECCMID abstract no.3200) has recently observed that isolation of Pseudomonas aeruginosa in sputum of patients hospitalized for acute COPD exacerbation (Chronic Obstructive Pulmonary Disease) is associated with increased 3-year mortality, independent of respiratory function and age. Analyses carried out in Barcelona from March 2006 to May 2007 by J.A. Martínez, J.M. Nicolás and colleagues (ECCMID abstract no.1501) reveal the role of different antibiotics classes on the risk of acquisition of resistant micro-organisms, especially in critical patients, characterized by an almost universal exposure to different antimicrobials. Exposure to cephalosporins (particularly ceftazidime) was associated with the greatest risk of resistant bacteria isolation. Specific antibodies produced in laboratory could be an attractive method for treating gram negative bacteria, because these experimental drugs (acting on different "pathogenic" targets) are less likely to develop resistance compared to conventional antibiotics (S Palliyil, A.J. Porter et al. - ECCMID abstract no.1167).

In the near future, physicians may face the spectre of having to treat serious infections without effective antimicrobials, as a result of growing antimicrobial resistance. Some infectious diseases could become almost untreatable as a consequence of the increasing multi-drug resistant bacterial strains and the very limited availability of new antibiotics (that is what's happening with the new extremely resistant forms of tuberculosis). "The point is that very few antimicrobial agents have been developed during the last decades, while antibiotic resistance has increased dramatically". Furthermore, "all the new molecules recently developed by the pharmaceutical industry lack the wide range of antibacterial action that characterized many traditional antibiotics, thus restricting their use only to specific infections and prompting the physicians' need for more accurate diagnosis and broader knowledge in this field". The problem is compounded by the withdrawal of interest of pharmaceutical industries in research and development in this field: "why they should invest huge amounts of money in developing treatments that people use just for few days, while hypertension and other chronic diseases are treated every day for several decades?", asked Prof Baquero. "Twenty-five percent of people with gram-negative septicaemia currently die; despite this, the development of new antimicrobials in this area is woefully inadequate: this is not acceptable in the XXI century", stated Prof. Baquero.

The strong institutional pressure for limiting the number of antibiotic prescriptions sometimes leads many patients and physicians to consider these drugs as something to avoid: "this is not correct", said Prof. Baquero. "Antimicrobial drugs must be regarded as an essential tool in daily medical practice, despite this crisis which is seriously undermining the effective treatment of many infections, even of life-threatening ones: "the issue is that antibiotics are frequently misused and abused, but in some cases their use is wrongly restricted", remarked Prof. Baquero. "Extended use of antibiotics might increase the individual risk of generating resistant microorganisms, in the same way that tobacco use increases the risk of lung cancer". Therefore, in order to lower antimicrobial resistance, proper antibiotic therapies should be tailored to individual patients, and patients must cooperate with their physicians, following carefully their instructions, especially in relation to the duration of the antibiotic treatment. The effectiveness of this cultural fight seems to be confirmed by a survey carried out in France (C. Van Dijken, P. Dellamonica et al. - ECCMID abstract no.1654), aimed to assess trends in antibiotic prescription among children attending day-care centres following promotion of prudent antibiotic use (PAU) in uncomplicated paediatric respiratory tract infections (RTI). Authors have shown that interventions advising PAU were effective in RTI management and fewer children were treated with antibiotics, as rhinopharyngitis (which doesn't require treatment with antibiotics) accounted for a lower proportion of prescriptions after the educational intervention. "Unjustified prescriptions (when no use of antibiotics is indicated), inappropriate prescriptions (errors in the choice of antibiotic or in the duration of the treatment), and self-medication should be eradicated if possible; direct consultation of a medical microbiologist or a specialist in infectious diseases, and patient-oriented educational programs may lead to a significant reduction of misuse and abuse, thus decreasing the risk of generating potential untreatable diseases", concluded Prof. Baquero.

European Congress of Clinical Microbiology and Infectious Diseases