Nuevos antibióticos para el tratamiento de las infecciones por microorganismos multirresistentes / New antibiotics for the treatment of infections by multidrug-resistant microorganisms

Una de las prioridades actuales de la Organización Mundial de la Salud son las bacterias multirresistentes, dado que constituyen un problema en todo el mundo por su rápida diseminación, así como por la dificultad de su tratamiento. Además, se asocian a una alta morbilidad, mortalidad y a unos costes económicos elevados. Hay bacterias multirresistentes tanto grampositivas como gramnegativas, destacando entre ellas Pseudomonas aeruginosa y Acinetobacter baumannii resistentes a las carbapenemas, enterobacterias productoras de carbapenemasas, Staphylococcus aureus resistente a la meticilina y/o con sensibilidad intermedia a la vancomicina y Enterococcus faecium (y menos frecuentemente Enterococcus faecalis) resistente a la vancomicina. En esta revisión se comentarán los nuevos antibióticos que se han incorporado en los últimos años al arsenal terapéutico, así como otros antibióticos prometedores que se encuentran en sus últimas fases de desarrollo

One of the current priorities of the World Health Organization is multidrug-resistant bacteria, because they are a global problem due to their rapid spread and the difficulty of their treatment. In addition, they are associated with high morbidity, mortality and high economic costs. There are multidrug-resistant bacteria, both Gram-positive and Gram-negative, including Pseudomonas aeruginosa and Acinetobacter baumannii resistant to carbapenems, enterobacteria producing carbapenemases, Staphylococcus aureus resistant to methicillin and/or with intermediate sensitivity to vancomycin, and Enterococcus faecium (and less frequently Enterococcus faecalis) resistant to vancomycin. This review will comment on the new antibiotics that have been incorporated into the therapeutic arsenal in recent years, as well as other promising antibiotics that are in their final stages of development

Clinical significance of coryneform Gram-positive rods from blood identified by MALDI-TOF mass spectrometry and their susceptibility profiles - a retrospective chart review.

With the advent of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), most Gram-positive rods (GPRs) are readily identified; however, their clinical relevance in blood cultures remains unclear. Herein, we assessed the clinical significance of GPRs isolated from blood and identified in the era of MALDI-TOF MS. A retrospective chart review of patients presenting to the Mayo Clinic, Rochester, MN, from January 1, 2013, to October 13, 2015, was performed. Any episode of a positive blood culture for a GPR was included. We assessed the number of bottles positive for a given isolate, time to positivity of blood cultures, patient age, medical history, interpretation of culture results by the healthcare team and whether infectious diseases consultation was obtained. We also evaluated the susceptibility profiles of a larger collection of GPRs tested in the clinical microbiology laboratory of the Mayo Clinic, Rochester, MN from January 1, 2013, to October 31, 2015. There were a total of 246 GPRs isolated from the blood of 181 patients during the study period. 56% (n = 101) were deemed contaminants by the healthcare team and were not treated; 33% (n = 59) were clinically determined to represent true bacteremia and were treated; and 8% (n = 14) were considered of uncertain significance, with patients prescribed treatment regardless. Patient characteristics associated with an isolate being treated on univariate analysis included younger age (P = 0.02), identification to the species level (P = 0.02), higher number of positive blood culture sets (P < 0.0001), lower time to positivity (P < 0.0001), immunosuppression (P = 0.03), and recommendation made by an infectious disease consultant (P = 0.0005). On multivariable analysis, infectious diseases consultation (P = 0.03), higher number of positive blood culture sets (P = 0.0005) and lower time to positivity (P = 0.03) were associated with an isolate being treated. 100, 83, 48 and 34% of GPRs were susceptible to vancomycin, meropenem, penicillin and ceftriaxone, respectively.

Plasmid-mediated transfer of the bla(NDM-1) gene in Gram-negative rods.

The latest threat of multidrug-resistant Gram-negative bacteria corresponds to the emergence of carbapenemase NDM-1 (New Delhi metallo-ß-lactamase) producers, mostly in Enterobacteriacae. Five bla(NDM) (-1) -positive plasmids of different incompatibility groups (IncL/M, FII, A/C and two untypeable plasmids) from clinical Enterobacteriaceae were evaluated for conjugation properties and host specificity. Successful conjugative transfers were obtained using all tested enterobacterial species as recipients (Escherichia coli, Klebsiella pneumoniae, Salmonella typhimurium and Proteus mirabilis) and all plasmid types. Conjugation frequencies varied from 1 × 10(-4) to 6 × 10(-8) transconjugants per donor. Higher conjugation rates were obtained for two plasmids at 30 °C compared with that observed at 25 and 37 °C. Carbapenems used as selector did not lead to higher conjugation frequencies. None of the five plasmids was transferable to Acinetobacter baumannii or Pseudomonas aeruginosa by conjugation. This work underlines how efficient the spread of the carbapenemase bla(NDM) (-1) gene could be among Enterobacteriaceae.

An 8-week, randomized, controlled, clinical study of the use of a 0.1% chlorhexidine mouthwash by chronic periodontitis patients.

AIM: To evaluate the efficacy of a 2-week administration of a 0.1% chlorhexidine mouthwash in the short-term treatment of chronic periodontitis patients and the impact of this product when administered twice by pocket irrigation. METHODS: Sixty patients were enrolled in a single-centre, placebo-controlled, randomized study with the blind allocation of product to two parallel groups. Clinical assessments were performed, and samples from six selected subgingival sites were collected for microbial analysis by culture at baseline, D15 and D56. Three of the six sites were randomly selected and were treated by subgingival irrigation with the same 0.1% chlorhexidine product at D0 and D7. A subsequent statistical analysis was performed using the paired Student's t-test and Wilcoxon rank sum test for within-group analyses; analysis of variance and the Kruskall-Wallis test were used for between-group analyses. RESULTS: Two-week treatment with a 0.1% chlorhexidine mouthwash slightly reduced the gingival inflammation associated with periodontitis. We observed a significant decrease in Gram-negative, facultative anaerobes and micro-aerophiles, and a significant increase in Gram-positive cocci. No increase in the treatment effect was demonstrated by irrigation of the periodontal pockets. CONCLUSION: The 0.1% chlorhexidine mouthwash showed limited beneficial effects in the treatment of periodontitis patients.

Antibiotic resistance in lactic acid bacteria and Micrococcaceae/Staphylococcaceae isolates from artisanal raw milk cheeses, and potential implications on cheese making.

Antibiotic susceptibility against 19 antimicrobial agents was evaluated in isolates of the genera Lactococcus (46 isolates), Leuconostoc (22), Lactobacillus (19), Staphylococcus (8), Enterococcus (7), and Microccoccus/Kocuria (5) obtained from the predominant microflora of nonrecent and recent types of artisanal raw cow's milk cheeses. Beta-lactams showed broad activity against all genera, although leuconostocs and lactobacilli were highly resistant to oxacillin (80% to 95.5%). Resistance to aminoglycosides was frequent for lactococci and enterococci (particularly for streptomycin), whereas lower rates of resistance were detected for lactobacilli and leuconostocs. Technologically interesting traits for the food industry were distributed among isolates that showed different degrees of resistance to common antibiotics. However, isolates showing resistance to less than 2 antibiotics were mainly those with properties of greatest technological interest (acidifying activity, proteolytic/lipolytic activities, or diacetyl production).

Nosocomial contamination of laryngoscope handles: challenging current guidelines.

BACKGROUND: Laryngoscope blades are often cleaned between cases according to well-defined protocols. However, despite evidence that laryngoscope handles could be a source of nosocomial infection, neither our institution nor the American Society of Anesthesiologists has any specific guidelines for handle disinfection. We hypothesized that laryngoscope handles may be sufficiently contaminated with bacteria and viruses to justify the implementation of new handle-cleaning protocols. METHODS: Sixty laryngoscope handles from the adult operating rooms were sampled with premoistened sterile swabs. Collection was performed between cases, in operating rooms hosting a broad variety of subspecialty procedures, after the room and equipment had been thoroughly cleaned for the subsequent case. Samples from 40 handles were sent for aerobic bacterial culture, and antimicrobial susceptibility testing was performed for significant isolates. Samples from 20 handles were examined for viral contamination using a polymerase chain reaction assay that detects 17 respiratory viruses. RESULTS: Of the 40 samples sent for culture, 30 (75%) were positive for bacterial contamination. Of these positive cultures, 25 (62.5%) yielded coagulase-negative staphylococci, seven (17.5%) Bacillusspp. not anthracis, three (7.5%) alpha-hemolytic Streptococcusspp., and one each (2.5%) of Enterococcusspp., Staphylococcus aureus(S. aureus), and Corynebacteriumspp. No vancomycin-resistant enterococci, methicillin-resistant S. aureus, or Gram-negative rods were detected. All viral tests were negative. CONCLUSION: We found a high incidence of bacterial contamination of laryngoscope handles despite low-level disinfection. However, no vancomycin-resistant enterococci, methicillin-resistant S. aureus, Gram-negative rods, or respiratory viruses were detected. Our results support adoption of guidelines that include, at a minimum, mandatory low-level disinfection of laryngoscope handles after each patient use.

[Antimicrobial effect of 4-(adamantyl-1)-1-(1-aminobutyl)benzol].

Antimicrobial activity in vitro of adamantine derivative in respect of aerobic and anaerobic microorganisms has been studied. In these conditions Gram-positive bacteria and some representatives of Gram-negative microorganisms (Shigella flexneri, S. newvcastle, Enterobacter aerogenes etc.) had maximal sensitivity (MIC 0.6-5.0 and 0.1-5.0 mg/ml, respectively). Pseudomonas aeruginosa were resistant to this substance (MIC >1 mg/ml).

Inhibition of Listeria innocua and Brochothrix thermosphacta in vacuum-packaged meat by addition of bacteriocinogenic Lactobacillus curvatus CRL705 and its bacteriocins.

AIMS: To evaluate the inhibition effectiveness of Lactobacillus curvatus CRL705 used as a bioprotective culture and of its bacteriocins, lactocin 705 and lactocin AL705, against Listeria innocua, Brochothrix thermosphacta and indigenous lactic acid bacteria (LAB) in vacuum-packaged meat stored at 2 degrees C. METHODS AND RESULTS: The live culture of Lact. curvatus CRL705 as well as synthetic lactocin 705 and purified lactocin AL705 were shown to be similarly effective in preventing the growth of B. thermosphacta and L. innocua in meat discs in contrast to control samples in which these micro-organisms grew rapidly, their numbers increasing by 3.0- and 2.1-log cycles respectively. In addition, indigenous LAB population showed a lower growth rate in the presence of lactocin 705. Bacteriocin activity was detected in the meat discs during 36 days at 2 degrees C irrespective of the biopreservation strategy applied. Changes in pH were not significantly different in meat discs treated with the protective culture when compared with control samples. CONCLUSIONS: Lactobacillus curvatus CRL705 and the produced bacteriocins, lactocin 705 and lactocin AL 705, were effective in inhibiting L. innocua and B. thermosphacta. The use of the bioprotective culture in refrigerated vacuum-packaged fresh meat would be more feasible from an economic and legal point of view. SIGNIFICANCE AND IMPACT OF THE STUDY: Establishment of biopreservation as a method to ensure the microbiological safety of vacuum-packaged fresh meat at 2 degrees C.

[In-vitro susceptibilites to levofloxacin and various antibacterial agents of 18,639 clinical isolates obtained from 77 centers in 2004].

A total of 18,639 clinical isolates in 19 species collected from 77 centers during 2004 in Japan were tested for their susceptibility to fluoroquinolones (FQs) and other selected antibiotics. The common respiratory pathogens, Streptococcus pyogenes, Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae showed a high susceptible rate against FQs. The isolation rate of beta lactamase non-producing ampicillin-resistant H. influenzae was approximately three times as large as those of western countries. Most strains of Enterobacteriaceae were also susceptible to FQs. The resistance rate of Escherichia coli against FQs has however been rapidly increasing so far as we surveyed since 1994. The FQs-resistant rate in methicillin-resistant Staphylococcus aureus (MRSA) showed approximately 90% except for 36%. of sitafloxacin while FQs-resistant rate in methicillin-susceptible S. aureus (MSSA) was around 5%. The FQs-resistant rate of methicillin-resistant coagulase negative Staphylococci (MRCNS) was also higher than that of methicillin-susceptible coagulase negative Staphylococci (MSCNS), however, it was lower than that of MRSA. In Pseudomonas aeruginosa clinical isolates, 32-34% from UTI and 15-19% of from RTI was resistant to FQs. Acinetobacter spp. showed a high susceptibility to FQs. Although FQs-resistant Neisseria gonorrhoeae have not been increased in western countries, it is remarkably high in Japan. In this survey, isolates of approximately 85% was resistant to FQs.

Antimicrobial activity of doripenem (S-4661): a global surveillance report (2003).

The spectrum of activity and potency of doripenem, a broad-spectrum parenteral carbapenem currently in clinical development, was evaluated using 16 008 clinical bacterial isolates collected as part of an international surveillance project during 2003. Using reference broth microdilution methods, doripenem was found to be highly active against oxacillin-susceptible Staphylococcus aureus and coagulase-negative staphylococci (2705 and 297 isolates, respectively; MIC90s 0.06 mg/L), with a potency greater than that of other carbapenem antibiotics. Against enterococci (1474 isolates), with the exception of Enterococcus faecium, doripenem displayed modest activity (MIC50 4). Doripenem was among the most potent agents tested against Streptococcus pneumoniae, viridans group streptococci and beta-haemolytic streptococci (885, 140 and 397 isolates; MIC(90)s 0.5, 0.5 and 0.03 mg/L, respectively). For Enterobacteriaceae (> 6200 isolates), doripenem was four- to 32-fold more active than imipenem against wild-type isolates (MIC90s 0.03-0.5 mg/L). MIC90s for confirmed extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae (121 and 155 isolates; 0.06 and 0.12 mg/L, respectively) were two-fold higher than for wild-type isolates. Doripenem was also active against Citrobacter spp., Enterobacter spp. and Serratia spp. (MIC90s 0.06-0.25 mg/L), including ceftazidime-resistant isolates. Doripenem and meropenem were the most active agents among all beta-lactams against Pseudomonas aeruginosa (829 isolates; MIC50/90s 0.5/8 and 0.5/16 mg/L, respectively), whereas doripenem and imipenem were the most active agents against Acinetobacter spp. (155 isolates; MIC50/90s 0.5/4 and

Rifaximin: in vitro and in vivo antibacterial activity--a review.

In vitro inhibitory activity of rifaximin is directed against Gram-positive and Gram-negative, aerobic and anaerobic bacteria. It is effective in the treatment of gastrointestinal infections when given orally because of the high concentration of the drug remaining in the gut lumen. Laboratory investigations have been carried out to assess the in vitro activity of rifaximin on different bacterial strains isolated from both human and domestic animals. The objective of this project is to review the in vitro and in vivo activity of rifaximin against bacterial infection with Gram-negative rods, Gram-positive rods and Gram-positive cocci and their resistance to rifaximin. The available data suggest that rifaximin is active in vitro and in vivo in the treatment of bacterial infection of adults and children.

Antimicrobial therapy of infections with aerobic Gram-positive rods.

This review presents data on in vitro susceptibilities of aerobically growing Gram-positive rods and in vivo activities of antibiotics used against Gram-positive rods. While in some instances susceptibility and efficacy are predictable (e.g. penicillin vs. Listeria and microaerophilic coryneforms, or metronidazole vs. Gardnerella) susceptibility testing by dilution techniques seems necessary for many Gram-positive rods as long as they are deemed clinically relevant.

Results of the 1997 SENTRY Antimicrobial Surveillance Program in three Brazilian medical centers

The SENTRY Antimicrobial Surveillance Program began in January, 1997, and is designed to monitor nosocomial and selected community acquired infections via a worldwide surveillance network of sentinel hospitals distributed equally by geographic location and size. Three sites in Brazil - Rio de Janeiro, Florianópolis, and Säo Paulo - participated in the SENTRY Antimicrobial Surveillance Program stet. Rank order of occurrence and antimicrobial susceptibillity of pathogenic species causing bloodstream infections, pneumonia, wound or skin and soft tissue infections, and urinary tract infections (UTI) in hospitalized patients were determined by collecting consecutive isolates over a specified period of time. Antimicrobial susceptibilities of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis obtained from outpatients with respiratory tract infections were also evaluated. The isolates for the evaluated infections were: 1) bloodstream - 20 consecutive isolates in each calendar month during a 12-month period; 2) pneumonia - 100 consecutive isolates over a 6 month period; 3) wound or skin and soft tissue - 50 consecutive isolates over a 3 month period; and 4) UTI - 50 consecutive isolates over a 3 month period. Each hospital also contributed, over a 6 month period, consecutive clinically significant outpatient isolates (one isolate per patient) of S. pneumoniae, H. influenzae, and M. catarrhalis that were considered pathogens in respiratory tract infections. Data collected for each isolate included species identification, antimicrobial susceptibility profile, data of isolation, and specimen type. Molecular studies were performed on selected isolates. A total of 1,241 bacterial strains were obtained; the majority were cultured from hospitalized patients, while 139 were fastidious organisms from community acquired respiratory tract infections. Gram-negative bacilli and S. aureus were the predominant pathogens, and Enterobacter spp. was a significant pathogen. The predominance of P. aeruginosa and Acinetobacter spp. and the significant levels of resistence to most agents are of major concern, as is the epidemic rate of ESBL-producing strains of Klebsiella spp. and E. coli in Brazil, which is much higher than rates seen in other areas of the world. Resistance among P. aeruginosa and the Enterobacteriaceae to fluoroquinolones, oxacillin-resistant S. aureus, and penicillin- and trimethoprim-sulfamethoxazole-resistant pneumococci were other...

Survey of anaerobic susceptibility patterns: a French multicentre study.

In 1996, the in vitro antibiotic susceptibility of 463 anaerobes was measured in five hospitals using the reference agar dilution method. None of the 209 B. fragilis group strains showed resistance to imipenem or ticarcillin-clavulanic acid. High resistance rates (29%) were observed for cefotetan and clindamycin. beta-Lactamase production was detected respectively in 64% of the Prevotella and 7% of the Fusobacterium strains. Because the same standardized methods were used for many years, the authors were able to evaluate the evolution of antibiotic resistance. Clindamycin resistance had increased within the B. fragilis group (from 14% in 1992 to 29% in 1996) and also among strains of clostridia (32%), P. acnes (18%) and Peptostreptococcus (28%). In the B. fragilis group multidrug resistance was unlikely to occur.

Identification and antibiotic sensitivity of bacteria isolated from periapical lesions.

Periradicular tissues from 28 refractory endodontic cases requiring surgical intervention were submitted for histological diagnosis and microbiological culture. Bacteria isolated from these lesions were identified and then tested for their antibiotic sensitivity to a panel of common antibiotics. The periapical tissue specimens of 22 out of 28 lesions (79%) contained microorganisms. Of the 22 cases showing positive growth cultures, 15 were polymicrobial and 7 were single species isolates. Fifty-three different species were recovered: 29 anaerobes, 19 facultative anaerobes, and 5 aerobes. Microbes were observed under light microscopy in only one case. The most common organisms isolated were Propionibacterium acnes, Staphylococcus epidermidis, Streptococcus intermedius, Wolinella recta, Fusobacterium species, and Clostridium species. Antibiotic susceptibility results showed no clear cut evidence of significant antibiotic resistance among the species tested. The results of this study seem to corroborate earlier studies regarding the microbial population of periapical lesions refractory to nonsurgical endodontics.

Effects of chronic isoproterenol treatment or submandibular and sublingual ablation on microflora of mouse tooth surfaces.

BALB/cA mice were examined for the effects of chronic isoproterenol treatment or submandibular-sublingual gland ablation on the natural patterns of oral bacterial colonization on tooth surfaces. Indigenous microflora on the tooth surfaces of BALB/cA mice was relatively simple. The predominant bacterial groups were Enterobacteriaceae (45.9%), enterococci (29.4%) and staphylococci (15.7%). Isoproterenol, which resulted in the induced synthesis of proline-rich proteins, caused a decrease in the total cultivable bacteria on the tooth surfaces. The proportion of Enterobacteriaceae in the isoproterenol-treated mice decreased, although the proportion of other bacterial groups increased. Salivary gland ablation, which caused the loss of mucins in saliva, showed essentially the same number of total bacteria as the control. Salivary gland ablation resulted in a decrease in the proportion of Enterobacteriaceae, while the proportion of Gram-positive rods and staphylococci increased.

Bactericidal activity of a fermented hot-water extract from Stevia rebaudiana Bertoni towards enterohemorrhagic Escherichia coli O157:H7 and other food-borne pathogenic bacteria.

A fermented aqueous extract from Stevia rebaudiana Bertoni showed strong bactericidal activity towards a wide range of food-borne pathogenic bacteria including enterohemorrhagic Escherichia coli O157:H7. The colony-forming ability of the food-borne pathogenic bacteria tested so far was reduced to < 10(-7) when exposed to > or = 40% (v/v) solutions of the fermented extract at 37 C for 2 hr. Secretion of verocytotoxin 1 and 2 by enterohemorrhagic E. coli was also diminished by fermented extract at a concentration of > or = 10% (v/v). In contrast, the fermented extract did not significantly kill Bifidobacteria or Lactobacilli. The active principle(s) of the fermented Stevia extract were bactericidal under acidic conditions.

Dentine tubule infection and endodontic therapy implications.

A critical review of the literature suggests that the microenvironment of dentinal tubules appears to favour the selection of relatively few bacterial types irrespective of the aetiology of the infection process; coronal dental caries or pulpar necrosis. These bacteria may constitute an important reservoir from which root canal infection and reinfection may occur following pulp necrosis or during and after endodontic treatment. Previous studies of this microflora have utilized microbiological culture techniques which need to be supplemented by those that allow in situ demonstration as well as identification of the bacteria. Newer treatment strategies that are designed to eliminate this microflora must include agents that can penetrate the dentinal tubules and destroy these microorganisms, since they are located in an area beyond the host defence mechanisms where they cannot be reached by systemically administered antimicrobial agents.

Impact of the agar medium and disc type on disc diffusion susceptibility testing against teicoplanin and vancomycin.

Susceptibility to teicoplanin and vancomycin was assessed by three disc types: two commercially available discs (NeoSensitabs and PDM disc (30 micrograms)) and one locally prepared 30 micrograms disc (SS disc) on four different medium types: Mueller-Hinton agar (MH medium), MH medium and PDM agar II supplemented with 5% horse blood (HMB medium and PDM medium, respectively), and Danish blood agar (DBA medium). Two previously studied groups of Gram-positive bacteria were tested: group B (N = 75) comprised miscellaneous cocci, and group C (N = 59) mostly rods. With NeoSensitabs, mean zone diameters were larger than with PDM and SS discs on all medium types, and mean zone diameters were larger on DBA medium than on MHB and PDM medium with all disc types. The impact of the medium type on the zone diameter was evaluated for 121 strains growing on MHB medium, PDM medium, and DBA medium. Bacterial groups B and C each divided into three MIC groups were analysed separately. We compared mean zone diameters for each specific group with the average zone diameter, i.e. the mean value for all zone diameters obtained. The smallest deviations from the average zone diameters were observed on PDM medium for both teicoplanin and vancomycin. Thirty-seven percent of strains failed to grow on MH medium, but supplementation of MH medium with horse blood significantly reduced the zone diameter for group B strains both for teicoplanin and vancomycin. Poor predictability of MIC from the zone diameter was found especially for strains with MICs < or = 1 microgram/ml. The medium type hardly affected the results of regression analysis. In contrast, the medium type markedly affected the results of error-rate bounded analysis. No errors were recorded with the SS disc on MHB medium for either teicoplanin or vancomycin, but no strains with MICs of vancomycin within the intermediate group could be correctly classified on DBA medium.