Evolutionary Pathways and Trajectories in Antibiotic Resistance.

Evolution is the hallmark of life. Descriptions of the evolution of microorganisms have provided a wealth of information, but knowledge regarding "what happened" has precluded a deeper understanding of "how" evolution has proceeded, as in the case of antimicrobial resistance. The difficulty in answering the "how" question lies in the multihierarchical dimensions of evolutionary processes, nested in complex networks, encompassing all units of selection, from genes to communities and ecosystems. At the simplest ontological level (as resistance genes), evolution proceeds by random (mutation and drift) and directional (natural selection) processes; however, sequential pathways of adaptive variation can occasionally be observed, and under fixed circumstances (particular fitness landscapes), evolution is predictable. At the highest level (such as that of plasmids, clones, species, microbiotas), the systems' degrees of freedom increase dramatically, related to the variable dispersal, fragmentation, relatedness, or coalescence of bacterial populations, depending on heterogeneous and changing niches and selective gradients in complex environments. Evolutionary trajectories of antibiotic resistance find their way in these changing landscapes subjected to random variations, becoming highly entropic and therefore unpredictable. However, experimental, phylogenetic, and ecogenetic analyses reveal preferential frequented paths (highways) where antibiotic resistance flows and propagates, allowing some understanding of evolutionary dynamics, modeling and designing interventions. Studies on antibiotic resistance have an applied aspect in improving individual health, One Health, and Global Health, as well as an academic value for understanding evolution. Most importantly, they have a heuristic significance as a model to reduce the negative influence of anthropogenic effects on the environment.

Selection versus transmission: Quantitative and organismic biology in antibiotic resistance.

We aimed to determine the importance of selection (mostly dependent on the anthropogenic use of antimicrobials) and transmission (mostly dependent on hygiene and sanitation) as drivers of the spread of antibiotic-resistant bacterial populations. The first obstacle to estimating the relative weight of both independent variables is the lack of detailed quantitative data concerning the number of bacterial cells, potentially either pathogenic or harmless, and bacterial species exposed to antimicrobial action in the microbiotas of specific environments. The second obstacle is the difficulty of considering the relative importance of the transmission and selection exerting their combined effects on antibiotic resistance across eco-biological levels. As a consequence, advances are urgently required in quantitative biology and organismic biology of antimicrobial resistance. The absolute number of humans exposed to antibiotics and the absolute number of potentially pathogenic and commensal bacteria in their microbiomes should influence both the selection and transmission of resistant bacterial populations. The "whole Earth" microbiome, with astonishingly high numbers of bacterial cells and species, which are also exposed to anthropogenic antimicrobials in various biogeographical spaces, shapes the antibiotic resistance landscape. These biogeographical spaces influence various intensities of selection and transmission of potentially pathogenic bacteria. While waiting for more precise data, biostatistics analysis and mathematical or computational modeling can provide proxies to compare the influence of selection and transmission in resistant bacteria. In European countries with lower sanitation levels, antibiotic consumption plays a major role in increasing antibiotic resistance; however, this is not the case in countries with high sanitation levels. Although both independent variables are linked, their relative influence on the level of antibiotic resistance varies according to the particular location. Therefore, interventions directed to decrease antibiotic resistance should be designed "a la carte" for specific locations with particular ecological conditions, including sanitation facilities.

High-density fecal Enterococcus faecium colonization in hospitalized patients is associated with the presence of the polyclonal subcluster CC17.

Enterococcus faecium belonging to the polyclonal subcluster CC17, with a typical ampicillin-resistant E. faecium (AREfm) phenotype, have become prevalent among nosocomial infections around the world. High-density intestinal AREfm colonization could be one of the factors contributing to the successful spread of these pathogens. We aimed to quantify the enterococcal intestinal colonization densities in stool samples from AREfm-colonized and non-colonized patients using fluorescent in situ hybridization (FISH). Stool samples were collected from AREfm-colonized (n = 8) and non-colonized (n = 8) patients. The relative number of Enterococcus faecalis and E. faecium was determined by FISH using specific 16S rRNA probes, while the total amount of bacterial cells was counted by staining the sample with 4',6-diamidino-2-phenylindole (DAPI). The median bacterial cell numbers in fecal samples, counted by DAPI staining, were 7.7 × 10(9) and 4.8 × 10(9) cells/g for AREfm-colonized and non-colonized patients, respectively (p = 0.34). The E. faecium densities in AREfm-colonized patients, accounting for 0.5-7% of all fecal bacterial cells, exceeded E. faecalis levels by over ten-fold. E. faecium was not detected in non-colonized patients. This study demonstrated high E. faecium cell densities in stool samples from patients colonized with AREfm. Increased cell densities may contribute to host-to-host transmission and environmental contamination, facilitating the spread of AREfm in the hospital setting.

Escherichia coli and Staphylococcus aureus: bad news and good news from the European Antimicrobial Resistance Surveillance Network (EARS-Net, formerly EARSS), 2002 to 2009.

Based on data collected by the European Antimicrobial Resistance Surveillance Network (EARS-Net) and the former EARSS, the present study describes the trends in antimicrobial susceptibility patterns and occurrence of invasive infections caused by Escherichia coli and Staphylococcus aureus in the period from 2002 to 2009. Antimicrobial susceptibility results from 198 laboratories in 22 European countries reporting continuously on these two microorganisms during the entire study period were included in the analysis. The number of bloodstream infections caused by E. coli increased remarkably by 71% during the study period, while bloodstream infections caused by S. aureus increased by 34%. At the same time, an alarming increase of antimicrobial resistance in E. coli was observed, whereas for S. aureus the proportion of meticillin resistant isolates decreased. The observed trend suggests an increasing burden of disease caused by E. coli. The reduction in the proportion of meticillin-resistant S. aureus and the lesser increase in S. aureus infections, compared with E. coli, may reflect the success of infection control measures at hospital level in several European countries.

Simulating the impact of non-pharmaceutical interventions limiting transmission in COVID-19 epidemics using a membrane computing model.

Epidemics caused by microbial organisms are part of the natural phenomena of increasing biological complexity. The heterogeneity and constant variability of hosts, in terms of age, immunological status, family structure, lifestyle, work activities, social and leisure habits, daily division of time and other demographic characteristics make it extremely difficult to predict the evolution of epidemics. Such prediction is, however, critical for implementing intervention measures in due time and with appropriate intensity. General conclusions should be precluded, given that local parameters dominate the flow of local epidemics. Membrane computing models allows us to reproduce the objects (viruses and hosts) and their interactions (stochastic but also with defined probabilities) with an unprecedented level of detail. Our LOIMOS model helps reproduce the demographics and social aspects of a hypothetical town of 10 320 inhabitants in an average European country where COVID-19 is imported from the outside. The above-mentioned characteristics of hosts and their lifestyle are minutely considered. For the data in the Hospital and the ICU we took advantage of the observations at the Nursery Intensive Care Unit of the Consortium University General Hospital, Valencia, Spain (included as author). The dynamics of the epidemics are reproduced and include the effects on viral transmission of innate and acquired immunity at various ages. The model predicts the consequences of delaying the adoption of non-pharmaceutical interventions (between 15 and 45 days after the first reported cases) and the effect of those interventions on infection and mortality rates (reducing transmission by 20, 50 and 80%) in immunological response groups. The lockdown for the elderly population as a single intervention appears to be effective. This modeling exercise exemplifies the application of membrane computing for designing appropriate multilateral interventions in epidemic situations.

High frequency of hypermutable Pseudomonas aeruginosa in cystic fibrosis lung infection.

The lungs of cystic fibrosis (CF) patients are chronically infected for years by one or a few lineages of Pseudomonas aeruginosa. These bacterial populations adapt to the highly compartmentalized and anatomically deteriorating lung environment of CF patients, as well as to the challenges of the immune defenses and antibiotic therapy. These selective conditions are precisely those that recent theoretical studies predict for the evolution of mechanisms that augment the rate of variation. Determination of spontaneous mutation rates in 128 P. aeruginosa isolates from 30 CF patients revealed that 36% of the patients were colonized by a hypermutable (mutator) strain that persisted for years in most patients. Mutator strains were not found in 75 non-CF patients acutely infected with P. aeruginosa. This investigation also reveals a link between high mutation rates in vivo and the evolution of antibiotic resistance.

Comparative genomics of Listeria species.

Listeria monocytogenes is a food-borne pathogen with a high mortality rate that has also emerged as a paradigm for intracellular parasitism. We present and compare the genome sequences of L. monocytogenes (2,944,528 base pairs) and a nonpathogenic species, L. innocua (3,011,209 base pairs). We found a large number of predicted genes encoding surface and secreted proteins, transporters, and transcriptional regulators, consistent with the ability of both species to adapt to diverse environments. The presence of 270 L. monocytogenes and 149 L. innocua strain-specific genes (clustered in 100 and 63 islets, respectively) suggests that virulence in Listeria results from multiple gene acquisition and deletion events.

[Importance of the antimicrobial spectrum and the bacterial resistances in the antibiotic choice for the treatment of pediatric patients with communitary infections]. / Importancia de la cobertura antimicrobiana y de las resistencias bacterianas en la elección de antibióticos en Pediatría.

OBJECTIVE: This study aimed to know the importance of the antimicrobial spectrum and the bacterial resistances for the antibiotic choice in the extrahospitalary pediatric area, at the same time that establish the relationship with others therapeutics parameters. MATERIAL AND METHODS: Cross-sectional, observational study within the MUSA (Improvement of Use of Antimicrobial Agents in Primary Health Care) Project made by personal interview of 210 pediatrician doctors randomly selected with national representation. This target is included in a bigger universe (855 doctors) representative of the most doctors responsible of the antibiotic prescriptions in the extrahospitalary area (sample error of the 3.3% for a 95% confidence interval and maximum response dispersion: p=q=50). The results of the pediatric study were subjected to a comparative analysis with the results of a similar study made ten years ago and with the global results of the general study. The questionnaire used for the interview had two clearly different parts: in the first part, the questions were open with the objective to get spontaneous answers from the participants; the second part had questions with suggested answers. RESULTS: Clinical efficacy is the most spontaneously valued issue by the Spanish pediatricians when it comes to choosing an antimicrobial agent; efficacy is followed by tolerance/safety and posology. Antimicrobial spectrum is mentioned by one out of 4-5 pediatricians that have participated in the study (21.9%), while the bacterial resistances are only mentioned by a 3.8%. In a suggested level, clinical efficacy is still the most valued parameter, being identified by 7 out of 10 interviewed with the bacterial eradication. In this case, the antimicrobial spectrum is the following parameter on significance, appearing as a synonym of "activity against specific microorganisms" in 2 out of 3 cases. In relation to his own evaluation, 3 out of 4 pediatricians say they take "a lot" of the bacterial resistances into consideration, who are mostly understood as "global rate" for 5-6 out of 10 interviewed, whether the resistance showed by the pneumococcal is what worried the most to 4 out of 10 of them. This importance given to the bacterial resistances at the second part of the study contrasts with the low consideration showed when it is compared with other parameters and the valoration is treated in a spontaneous way. In relation to a similar study realized on 1997 (Urano Proyect), we observe that clinical efficacy has replaced tolerance/safety as a parameter to bear in mind, probably as a consequence of more experience and confidence with the most important antimicrobial agents in the antibiotic prescriptions in podiatry. On the other hand, the bacterial resistances still being left out on the pediatricians spontaneous consideration, a fact that is shared with the majority of the collectives participating on the general study. The rest of the parameters stay in a similar way. CONCLUSIONS: Is necessary to emphasize at the importance of bacterial resistances in the antimicrobials rational use on the pediatric patient. As the antimicrobial tolerance profile has been improving in the last ten years, clinical efficacy, understood as "bacterial eradication" has became the most determining parameter when choosing antimicrobial agents.

Prevalence and spread of extended-spectrum beta-lactamase-producing Enterobacteriaceae in Europe.

Extended-spectrum beta-lactamases (ESBLs) represent a major threat among resistant bacterial isolates. The first types described were derivatives of the TEM-1, TEM-2 and SHV-1 enzymes during the 1980s in Europe, mainly in Klebsiella pneumoniae associated with nosocomial outbreaks. Nowadays, they are mostly found among Escherichia coli isolates in community-acquired infections, with an increasing occurrence of CTX-M enzymes. The prevalence of ESBLs in Europe is higher than in the USA but lower than in Asia and South America. However, important differences among European countries have been observed. Spread of mobile genetic elements, mainly epidemic plasmids, and the dispersion of specific clones have been responsible for the increase in ESBL-producing isolates, such as those with TEM-4, TEM-24, TEM-52, SHV-12, CTX-M-9, CTX-M-14, CTX-M-3, CTX-M-15 and CTX-M-32 enzymes.

Factors impacting on length of stay and mortality of community-acquired pneumonia.

A 1-year retrospective multicentre study was performed to identify factors influencing hospital length of stay (LOS) and mortality of patients (n = 3233) admitted to hospital because of community-acquired pneumonia (CAP). Pneumonia severity index (PSI) high-risk classes (IV and V), positive blood culture, admission to an intensive care unit (ICU), multi-lobar involvement and alcohol consumption were associated independently with prolonged LOS. Tobacco smoking was associated with a reduced LOS. The LOS varied markedly among centres. Only PSI high-risk class, admission to ICU and multi-lobar involvement were associated with early, late and global mortality. Positive blood cultures, antimicrobial therapy according to treatment guidelines and the establishment of an aetiological diagnosis were linked to reduced late and global mortality. These data suggest that early mortality associated with CAP is highly dependent on the clinical status of the patient at presentation. Conversely, late mortality seems to be associated more closely with clinical management factors; hence, an aetiological diagnosis and compliance with appropriate therapeutic guidelines have a significant influence on outcome.

Increasing prevalence of ESBL-producing Enterobacteriaceae in Europe.

Extended-spectrum beta-lactamases (ESBLs) have been increasingly reported in Europe since their first description in 1983. During the 1990s, they were described mainly as members of the TEM- and SHV-beta-lactamase families in Klebsiella pneumoniae causing nosocomial outbreaks. Nowadays, they are mostly found in Escherichia coli that cause community-acquired infections and with increasing frequency contain CTX-M enzymes. Dissemination of specific clones or clonal groups and epidemic plasmids in community and nosocomial settings has been the main reason for the increase in most of the widespread ESBLs belonging to the TEM (TEM-24, TEM-4, TEM-52), SHV (SHV-5, SHV-12) and CTX-M (CTX-M-9, CTX-M-3, CTX-M-14 or CTX-M-15) families in Europe. Co-selection with other resistances, especially to fluoroquinolones, aminoglycosides and sulfonamides, seems to have contributed to the problem. The emergence of epidemic clones harbouring several beta-lactamases simultaneously (ESBLs, metallo-beta-lactamases or cephamycinases) and of new mechanisms of resistance to fluoroquinolones and aminoglycosides warrants future surveillance studies.

Successful treatment of intrauterine cytomegalovirus infection with an intraventricular cyst in a dichorionic diamniotic twin gestation using cytomegalovirus immunoglobulin.

Congenital cytomegalovirus (CMV) infection is the leading cause of severe congenital abnormalities. CMV immunoglobulin (CMVIG) may lower risk for symptomatic disease in congenital CMV infection. In a twin pregnancy, only one fetus shows CMV infection, raising a dilemma about intervention since the uninfected fetus would be exposed to treatment unnecessarily. CMVIG (2 × 200 U/kg) was given due to high viral load and development of an intraventricular cyst. The cyst growth plateaued, no other brain damage developed, and at 8 months, the infant was symptom-free. CMVIG appears appropriate to treat intrauterine CMV infection in this setting.

Complex clonal and plasmid epidemiology in the first outbreak of Enterobacteriaceae infection involving VIM-1 metallo-beta-lactamase in Spain: toward endemicity?

BACKGROUND: We report the emergence and spread of metallo-beta-lactamases (MBLs) among enterobacterial isolates at Ramón y Cajal University Hospital (Madrid, Spain). METHODS AND RESULTS: During the period from March 2005 through September 2006, 25 patients (52% of whom were in the intensive care unit) were infected and/or colonized with single or different MBL-producing Enterobacteriaceae isolates (Klebsiella pneumoniae, 14 patients; Enterobacter cloacae, 12 patients; Escherichia coli, 1 patient; and/or Klebsiella oxytoca, 1 patient). Clonal analysis (XbaI pulsed-field gel electrophoresis) revealed that all K. pneumoniae isolates belonged to the same clone, but 6 patterns were found among the E. cloacae isolates. Carbapenems were affected to different degrees (minimum inhibitory concentration, < or = 1 to > 8 microg/mL), as were aminoglycosides and ciprofloxacin. The bla(VIM-1) MBL gene was present in all isolates; in addition, the bla(SHV-12) extended-spectrum beta-lactamase gene was detected in K. pneumoniae and E. coli isolates. The bla(VIM-1) gene was detected within a 4.0-kb class 1 integron (bla(VIM-1)-aacA4-dfrII-aadA1-catB2) in K. pneumoniae and E. coli and in a 2.5-kb class 1 integron (bla(VIM-1)-aacA4-aadA1) in E. cloacae and K. oxytoca isolates. The bla(VIM-1) gene was transferable (filter-mating) in 14 of 14 K. pneumoniae isolates, 4 of 11 E. cloacae isolates, and 1 of 1 E. coli isolate. A 60-kb plasmid belonging to the IncI1 group was detected in the epidemic VIM-1-K. pneumoniae clone. Plasmids of 300- or 435-kb belonging to IncH12 group were found among E. cloacae isolates. CONCLUSIONS: K. pneumoniae-MBL monoclonal epidemics coexisted with E. cloacae-MBL multiclonal epidemics in our hospital. The spread of the bla(VIM-1) gene among Enterobacteriaceae was driven by clonal spread associated with intergeneric plasmid transfer with different class I integron platforms. Such complex epidemiology might anticipate endemicity and should be considered for the design of containment epidemiology strategies.

Antibiotic consumption and generation of resistance in Streptococcus pneumoniae: the paradoxical impact of quinolones in a complex selective landscape.

The development of resistance to the different antibiotics by the majority of bacterial species of clinical importance seems unavoidable. However, not all drugs have the same efficiency to select for resistance. Large differences in the qualitative and quantitative consumption of antibiotics among countries are known to exist and several authors have consistently reported the direct relationship between consumption and selection of resistance for Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae and Escherichia coli and beta-lactams and macrolides use. In Spain, extensive surveillance started in 1996, and the Willow (SAUCE) Project, to monitor and update resistance in respiratory pathogens and to couple those data with data concerning national antibiotic consumption (IMS) from both a temporal and geographical approach. Temporally, despite a continuous increase of 16% in quinolone consumption from 1997 to 2001, basically due to the arrival of respiratory quinolones, levofloxacin and moxifloxacin, a continuous linear increase in the resistance rates to ciprofloxacin in S. pneumoniae was not observed. There also was an inverse correlation between provincial consumption of quinolones and resistance to ciprofloxacin. Several hypotheses are proposed and discussed to explain these apparent paradoxical observations, such as the replacement of ciprofloxacin by more potent antipneumococcal quinolones, the possibility of an antibiotic pressure threshold, the influence of other nonquinolone drugs on the expression of ciprofloxacin-resistance biological costs, and the influence of changes in temporal or spatial prevalence of particular clones.

Genetic and phenotypic differences among Enterococcus faecalis clones from intestinal colonisation and invasive disease.

This study investigated the differences among Enterococcus faecalis isolates from the intestinal compartment of healthy volunteers (n = 36), intensive care unit (ICU) patients (n = 29) and blood isolates (n = 31) from the same institution, in comparison with seven epidemic clones from other institutions. In general, isolates from colonised ICU patients and from bacteraemic patients showed higher rates of antimicrobial resistance than isolates from colonised healthy volunteers, particularly for erythromycin and aminoglycosides. The proportion of isolates/clone was 1.05 in the community, 2.63 in the ICU, and 1.47 among bacteraemic cases, suggesting low clonal variation in ICUs. Two clones, RENC1 and RENC2, were frequently found as intestinal colonisers of ICU patients, and RENC1 was also found to colonise healthy volunteers. These two clones were a cause of bacteraemia in the institution studied, and RENC2 was also detected in various other Spanish hospitals. Both RENC1 and RENC2 were esp+, bacteriocin producers, and were resistant to all antibiotics tested except vancomycin and ampicillin. RENC1 produced haemolysin whereas RENC2 produced protease. The ace, agg, cylA, esp and gelE genes were more common among colonising strains from ICU patients than among isolates from individuals in the community. In both colonised groups (ICUs and the community), 40-50% of isolates harbouring the gelE and cylA genes did not express the corresponding phenotypes. Thus, the study indicated that particular E. faecalis clones might be well-adapted to hospital environments, and that surveillance should be directed specifically towards rapid detection of these disseminating clones in order to prevent infections and clonal spread.

Genetic relatedness and antimicrobial resistance determinants among clinical isolates of enterococci from Cuba.

This study describes the genetic relationships and antimicrobial resistance determinants found among 99 clinical isolates of enterococci from 15 different hospitals in Cuba. Pulsed-field gel electrophoresis SmaI analysis demonstrated a high degree of genetic diversity. A limited number of multiresistant Enterococcus faecalis clones, showing resistance to three or more families of antimicrobial agents, were detected simultaneously in different institutions, suggesting inter-hospital circulation of selected clones, and/or selection of particular clones following their introduction into the hospital environment. Antimicrobial resistance determinants, including erm(B), aac(6')-aph(2'), aph(3'), ant(6), vanB (E. faecalis) and vanA (Enterococcus faecium) were detected by PCR in various isolates.

Streptococcus pneumoniae endophthalmitis: a study of 36 cases with special reference to antibiotic resistance and treatment options.

Patients (n = 36) diagnosed with pneumococcal endophthalmitis from six Spanish hospitals between 1986 and 2004 were studied retrospectively. The diagnosis was based on clinical findings, ophthalmological examination, and isolation of Streptococcus pneumoniae from vitreous and/or aqueous humours of 19 patients (definite diagnosis), and from other ocular specimens of 17 patients (probable diagnosis). The mean (+/- SD) age was 69.3 (+/- 16.5) years (range 1.5-89 years), and 20 (55.5%) patients were male. The origin of endophthalmitis was considered exogenous for 34 (94.5%) patients. The most common predisposing factors were previous ocular surgery (n = 25, 69.4%), ocular trauma (n = 5, 13.9%), and close-to-eye radiotherapy (n = 3, 8.3%). Eleven (30.5%) patients underwent evisceration as the first therapeutic measure (primary evisceration), and evisceration was performed after antibiotic treatment failure (secondary evisceration) for six (16.7%) patients. Primary evisceration was performed more commonly (63.6%) during 1998-2004, while secondary evisceration was only performed during 1986-1997. Eighteen (50%) patients received intra-vitreous antibiotics (mainly vancomycin), and 31 (86.1%) patients were given systemic antibiotic therapy. The most frequent pneumococcal serogroups isolated were 6, 19, 9, 15 and 23. Pulsed-field gel electrophoresis analysis of 23 isolates revealed that four belonged to the international clones Spain(23F)-1, Spain(6B)-2, Spain(9V)-3 and Sweden(15A)-25. Non-susceptibility rates (i.e., intermediately-resistant and resistant) were: co-trimoxazole, 44.8%; penicillin, 33.3%; tetracycline, 31.0%; erythromycin, 21.9%; chloramphenicol, 17.9%; rifampicin, 7.4%; cefotaxime, 5.9%; and levofloxacin, 0%. Although uncommon, pneumococcal endophthalmitis is a medical emergency because of the often aggressive clinical course, poor visual outcome and need for evisceration in a large proportion of patients.

In vitro activity of linezolid against Mycobacterium tuberculosis complex, including multidrug-resistant Mycobacterium bovis isolates.

The activity of linezolid was studied against 55 Mycobacterium tuberculosis (42 susceptible, 3 isoniazid resistant and 10 isoniazid and rifampicin resistant), one Mycobacterium bovis and two multidrug-resistant M. bovis isolates using the standard 7H10 agar proportion and the ESP Culture System II methods. Both methods displayed similar MIC(90) values (minimum inhibitory concentrations for 90% of the organisms) of 0.5mg/L; however, the former method yielded slightly lower MIC(50) values (MICs for 50% of the organisms) (0.25mg/L) compared with the latter method (0.5mg/L). No differences were observed between susceptible and resistant isolates, including multidrug-resistant M. bovis isolates, with a MIC range of 0.12-0.5mg/L. The potential role of linezolid in tuberculosis patients requires further in vivo evaluation.

[Patterns of susceptibility to antibiotics of Enterobacteriaceae causing intra-abdominal infection in Spain: SMART 2003 study outcomes]. / Patrones de sensibilidad a antimicrobianos de Enterobacteriaceae causantes de infecciones intraabdominales en España: resultados del estudio SMART 2003.

SMART (Study for Monitoring Antimicrobial Resistance Trends) is an ongoing global antimicrobial surveillance program focused on clinical isolates from intra-abdominal infections. The objective of this subanalysis was to assess antimicrobial susceptibility patterns among Entero-bacteriaceae recovered at 13 participating Spanish sites during 2003. Antimicrobial susceptibility testing was performed using broth microdilution techniques according to the CLSI (formerly NCCLS) guidelines for MIC testing. The presence of extended-spectrum beta-lactamases (ESBL) was confirmed in isolates with a MIC of ceftriaxone, ceftazidime, or cefepime>or=2 mg/l by comparing cefepime MICs with and with-out clavulanate. A total of 981 Enterobacteriaceae recovered from 840 patients were tested, of which 398 (41%) were community-acquired. Escherichia coli was the most common isolate (571 isolates; 58%), followed by Klebsiella spp. (153; 16% Enterobacter spp. (97; 10%), and Proteus spp. (63; 6%). A total of 191 isolates (19%) from 176 patients produced inducible beta-lactamases. The carbapenems and amikacin were the most consistently active agents against the Enterobacteriaceae (susceptibility>or=99%). Resistance rates for ceftazidime, cipro-floxacin, and levofloxacin exceeded 10%. ESBLs were detected phenotypically in 61 (6%) isolates, being the most common E. coli (61%), Klebsiella spp. (20%), and Enterobacter spp. (8%). Antimicrobial resistance among Enterobacteriaceae isolated from intra-abdominal infections is a problem in Spain. A significant proportion of inducible beta-lactamase and ESBL-producing Enterobacteriaceae causing intra-abdominal infection were acquired in the community. The carbapenems ertapenem, imipenem and meropenem and the aminoglycoside amikacin were highly active in vitro against Enterobacteriaceae isolated from intra-abdominal sites, including ESBL-producing organisms.

The refusal of the Society to accept antibiotic toxicity: missing opportunities for therapy of severe infections.

Over the last decade the emergence and spread of antibiotic resistance in bacteria has led to a new fear in the scientific and medical communities as well as among members of the general public. Due to the lack of development of new antibiotics, there is a need to reconsider old drugs or dosages rejected because of their toxicity. As a society, if we tolerate the potential toxicity of other drugs, such as anticancer drugs, why do we refuse to accept the use of toxic but effective antibiotics in life-threatening infections? The aim of this review is to provide insight into the reasons why the medical community remains unjustifiably unwilling to accept the risk of toxicity and the adverse effects of antibiotics that, nonetheless, might be required to treat severe infections, including those due to multidrug-resistant bacteria.