Cooccurrence of predominant Panton-Valentine leukocidin-positive sequence type (ST) 152 and multidrug-resistant ST 241 Staphylococcus aureus clones in Nigerian hospitals.

Ninety-six clinical isolates of Staphylococcus aureus from Nigeria were characterized phenotypically and genetically. Twelve multidrug-resistant methicillin (meticillin)-resistant S. aureus (MRSA) isolates carrying a new staphylococcal cassette chromosome mec element and a high proportion of Panton-Valentine leukocidin (PVL)-positive methicillin-susceptible S. aureus (MSSA) isolates were observed. The cooccurrence of multidrug-resistant MRSA and PVL-positive MSSA isolates entails the risk of emergence of a multidrug-resistant PVL-positive MRSA clone.

Preventive and therapeutic strategies in critically ill patients with highly resistant bacteria.

The antibiotic pipeline continues to diminish and the majority of the public remains unaware of this critical situation. The cause of the decline of antibiotic development is multifactorial and currently most ICUs are confronted with the challenge of multidrug-resistant organisms. Antimicrobial multidrug resistance is expanding all over the world, with extreme and pandrug resistance being increasingly encountered, especially in healthcare-associated infections in large highly specialized hospitals. Antibiotic stewardship for critically ill patients translated into the implementation of specific guidelines, largely promoted by the Surviving Sepsis Campaign, targeted at education to optimize choice, dosage, and duration of antibiotics in order to improve outcomes and reduce the development of resistance. Inappropriate antimicrobial therapy, meaning the selection of an antibiotic to which the causative pathogen is resistant, is a consistent predictor of poor outcomes in septic patients. Therefore, pharmacokinetically/pharmacodynamically optimized dosing regimens should be given to all patients empirically and, once the pathogen and susceptibility are known, local stewardship practices may be employed on the basis of clinical response to redefine an appropriate regimen for the patient. This review will focus on the most severely ill patients, for whom substantial progress in organ support along with diagnostic and therapeutic strategies markedly increased the risk of nosocomial infections.

Chemical modifications of a natural xanthone and antimicrobial activity against multidrug resistant Staphylococcus aureus and cytotoxicity against human tumor cell lines

A series of 15 ω-aminoalkoxylxanthones containing methyl, ethyl, propyl, tert-butylamino and piperidinyl moieties were synthesized from a natural xanthone isolated from a lichen species. These compounds were tested for their in vitro antibacterial properties against Gram-positive and Gram-negative bacteria and cytotoxicity against a number of human tumor cell lines was too evaluated. The newly synthesized derivatives revealed selective activity against Staphylococcus aureus (Gram-positive), and the most promising results are for a multidrug resistant strain, for which six of these compounds showed good activity (MICs 4 µg/mL). Many derivatives inhibited tumor cells growth and most compounds were active on multiple lines.

Rapid detection of multidrug-resistant Mycobacterium tuberculosis using the mycobacteria growth indicator tube (MGIT) system

The emergence of multidrug-resistant strains of Mycobacterium tuberculosis has increased the need for rapid drug susceptibility tests, which are needed for adequate patient treatment. The objective of the present study was to evaluate the mycobacteria growth indicator tube (MGIT) system to detect multidrug-resistant M. tuberculosis strains. The MGIT system was compared with two standard methods (proportion and resistance ratio methods). One hundred clinical M. tuberculosis isolates [25 susceptible to isoniazid (INH) and rifampicin (RIF), 20 resistant to INH, 30 resistant to INH-RIF, and 25 resistant to INH-RIF and other drugs] obtained in the State of São Paulo were tested for INH and RIF susceptibility. Full agreement among the tests was found for all sensitive and all INH-resistant strains. For RIF-resistant strains results among the tests agreed for 53 (96.4%) of 55 isolates. Results were obtained within 6 days (range, 5 to 8 days), 28 days and 12 days when using MGIT, the proportion method and the resistance ratio methods, respectively. The MGIT system presented an overall agreement of 96% when compared with two standard methods. These data show that the MGIT system is rapid, sensitive and efficient for the early detection of multidrug-resistant M. tuberculosis.

Factors associated with bacteremia due to multidrug-resistant Gram-negative bacilli in hematopoietic stem cell transplant recipients

The epidemiology of bacteremia developing during neutropenia has changed in the past decade, with the re-emergence of Gram-negative (GN) bacteria and the development of multidrug resistance (MDR) among GN bacteria. We conducted a case-control study in order to identify factors associated with bacteremia due to multidrug-resistant Gram-negative (MDRGN) isolates in hematopoietic stem cell transplant recipients. Ten patients with MDRGN bacteremia were compared with 44 patients with GN bacteremia without MDR. Bacteremia due to Burkholderia or Stenotrophomonas sp was excluded from analysis (3 cases), because the possibility of intrinsical resistance. Infection due to MDRGN bacteria occurred in 2.9% of 342 hematopoietic stem cell transplant recipients. Klebsiella pneumoniae was the most frequent MDRGN (4 isolates), followed by Pseudomonas aeruginosa (3 isolates). Among non-MDRGN, P. aeruginosa was the most frequent agent (34%), followed by Escherichia coli (30%). The development of GN bacteremia during the empirical treatment of febrile neutropenia (breakthrough bacteremia) was associated with MDR (P < 0.001, odds ratio = 32, 95% confidence interval = 5_190) by multivariate analysis. Bacteremia due to MDRGN bacteria was associated with a higher death rate by univariate analysis (40 vs 9%; P = 0.03). We were unable to identify risk factors on admission or at the time of the first fever, but the occurrence of breakthrough bacteremia was strongly associated with MDRGN bacteria. An immediate change in the antibiotic regimen in such circumstances may improve the prognosis of these patients.

Role of a GenoType MTBDRplus line probe assay in early detection of multidrug-resistant tuberculosis at a Brazilian reference center

Resistance to Mycobacterium tuberculosis is a reality worldwide, and its diagnosis continues to be difficult and time consuming. To face this challenge, the World Health Organization has recommended the use of rapid molecular tests. We evaluated the routine use (once a week) of a line probe assay (Genotype MTBDRplus) for early diagnosis of resistance and for assessment of the main related risk factors over 2 years. A total of 170 samples were tested: 15 (8.8%) were resistant, and multidrug resistance was detected in 10 (5.9%). The sensitivity profile took 3 weeks (2 weeks for culture and 1 week for rapid testing). Previous treatment for tuberculosis and the persistence of positive acid-fast smears after 4 months of supervised treatment were the major risk factors observed. The use of molecular tests enabled early diagnosis of drug-resistant bacilli and led to appropriate treatment of the disease. This information has the potential to interrupt the transmission chain of resistant M. tuberculosis.

Potential public health significance of faecal contamination and multidrug-resistant Escherichia coli and Salmonella serotypes in a lake in India

To assess the prevalence of faecal coliform bacteria and multiple drug resistance among Escherichia coli and Salmonella serotypes from Vembanadu Lake. Study design: Systematic microbiological testing. Methods: Monthly collection of water samples were made from ten stations on the southern and northern parts of a salt water regulator constructed in Vembanadu Lake in order to prevent incursion of seawater during certain periods of the year. Density of faecal colifrom bacteria was estimated. E. coli and Salmonella were isolated and their different serotypes were identified. Antibiotic resistance analysis of E. coli and Salmonella serotypes was done and the MAR index of individual isolates was calculated. Results: Density of faecal coliform bacteria ranged from mean MPN value 2900 -7100/100ml. Results showed multiple drug resistance pattern among the bacterial isolates. E. coli showed more than 50% resistance to amickacin, oxytetracycline, streptomycin, tetracycline and kanamycin while Salmonella showed high resistance to oxytetracycline, streptomycin, tetracycline and ampicillin. The MAR indexing of the isolates showed that they have originated from high risk source such as humans, poultry and dairy cows. Conclusions: The high density of faecal coliform bacteria and prevalence of multi drug resistant E. coli and Salmonella serotypes in the lake may pose severe public health risk through related water borne and food borne outbreaks

Isopimaric acid from Pinus nigra shows activity against multidrug-resistant and EMRSA strains of Staphylococcus aureus

The diterpene isopimaric acid was extracted from the immature cones of Pinus nigra (Arnold) using bioassay. guided fractionation of a crude hexane extract. Isopimaric acid was assayed against multidrug-resistant (MDR) and methicillin-resistant Staphylococcus aureus (MRSA). The minimum inhibitory concentrations (MIC) were 32-64 mu g/mL and compared with a commercially obtained resin acid, abietic acid, with MICs of 64 mu g/mL. Resin acids are known to have antibacterial activity and are valued in traditional medicine for their antiseptic properties: These results show that isopimaric acid is active against MDR an MRSA strains of S. aureus which are becoming, increasingly resistant to antibiotics. Both compounds were evaluated for modulation activity in combination with antibiotics, but did not potentiate the activity of the antibiotics tested. However, the compounds were also assayed in combination with the efflux pump inhibitor reserpine, to ice if inhibition of the TetK or NorA efflux pump increased their activity. Interestingly, rather than a potentiation of activity by a reduction in MIC, a two to four-fold increase in MIC was seen. It may he that isopimaric acid and abietic acid are not substrates for these efflux pumps, but it is also possible that an antagonistic interaction with reserpine may render the antibiotics inactive. H-1-NMR of abietic acid and reserpine taken individually and in combination, revealed a shift in resonance of some peaks for both compounds when mixed together compared with the spectra of the compounds on their own. It is proposed that this may he due to complex formation between abietic acid and reserpine and that this complex formation is responsible for a reduction in activity and elevation of MIC. Copyright (c) 2005 John Wiley & Sons, Ltd.

Epidemic multidrug-resistant (MDR-AmpC) Salmonella enterica serovar Newport strains contain three phage regions and a MDR resistance plasmid

Multidrug-resistant (MDR-AmpC) Salmonella enterica serovar Newport has caused serious disease in animals and humans in North America, whereas in the UK S. enterica serovar Newport is not associated with severe disease and usually sensitive to antibiotics; MDR S. Newport (not AmpC) strains have only been isolated from poultry. We found that UK poultry strains belonged to MLST type ST166 and were distinct from cattle isolates for being able to utilize D-tagotose and when compared by pulsed-field gel electrophoresis (PFGE), comparative genomic hybridization (CGH) and diversity arrays technology (DArT). Cattle strains belonged to the ST45 complex differing from ST166 at all seven loci. PFGE showed that 19 out of 27 cattle isolates were more than 85% similar to each other and some UK and US strains were indistinguishable. Both CGH and DArT identified genes (including phage-related ones) that were uniquely present in the US isolates and two such genes identified by DArT showed sequence similarities with the pertussis-like (artAB) toxin. This work demonstrates that MDR-AmpC S. Newport from the USA are genetically closely related to pan-susceptible strains from the UK, but contained three extra phage regions and a MDR plasmid.

Multidrug-resistant Shiga toxin-producing Escherichia coli in dogs with diarrhea

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Antimicrobial use and incidence of multidrug-resistant Pseudomonas aeruginosa in a teaching hospital: an ecological approach

Introduction: Multidrug-resistant Pseudomonas aeruginosa is a major threat in healthcare settings. The use of antimicrobials can influence the incidence of resistant strains by direct and indirect mechanisms. The latter can be addressed by ecological studies. Methods: Our group attempted to analyze the relation between the use of antipseudomonal drugs and the incidence of MDR-PA among 18 units from a 400-bed teaching hospital. The study had a retrospective, ecological design, comprising data from 2004 and 2005. Data on the use of four antimicrobials (amikacin, ciprofloxacin, ceftazidime and imipenem) were tested for correlation with the incidence of MDR-PA (defined as isolates resistant to the four antimicrobials of interest) in clinical cultures. Univariate and multivariate linear regression analyses were performed. Results: Significant correlations were determined between use and resistance for all antimicrobials in the univariate analysis: amikacin (standardized correlation coefficient = 0.73, p = 0.001); ciprofloxacin (0.71, p = 0.001); ceftazidime (0.61, p = 0.007) and imipenem (0.87, p < 0.001). In multivariate analysis, only imipenem (0.67, p = 0.01) was independently related to the incidence of multidrug-resistant strains. Conclusions: These findings share similarities with those reported in individual-based observational studies, with possible implications for infection control.

Trends in multidrug-resistant tuberculosis

Multidrug-resistant tuberculosis (MDR-TB) is an increasing global problem. The extent and burden of MDR-TB varies significantly from country to country and region to region. Globally, about three per cent of all newly diagnosed patients have MDR-TB and the proportion is higher in patients who had previously received anti-tuberculosis (anti-TB) treatment reflecting the failure of programs designed to ensure complete cure of patients with tuberculosis. The management of MDR-TB is a challenge that should be undertaken by experienced clinicians at centers equipped with reliable laboratory services and implementation of DOTS-Plus strategy.

Implication of the RDRio Mycobacterium tuberculosis sublineage in multidrug resistant tuberculosis in Portugal

Multidrug and extensively drug resistant Mycobacterium tuberculosis are a threat to tuberculosis control programs. Genotyping methods, such as spoligotyping and MIRU-VNTR typing (Mycobacterial Interspersed Repetitive Units), are useful in monitoring potentially epidemic strains and estimating strain phylogenetic lineages and/or genotypic families. M. tuberculosis Latin American Mediterranean (LAM) family is a major worldwide contributor to tuberculosis (TB). LAM specific molecular markers, Ag85C(103) single nucleotide polymorphism (SNP) and RDRio long-sequence polymorphism (LSP), were used to characterize spoligotype signatures from 859 patient isolates from Portugal. LAM strains were found responsible for 57.7% of all tuberculosis cases. Strains with the RDRio deletion (referred to as RDRio) were estimated to represent 1/3 of all the strains and over 60% of the multidrug resistant (MDR) strains. The major spoligotype signature SIT20 belonging to the LAM1 RDRio sublineage, represented close to 1/5th of all the strains, over 20% of which were MDR. Analysis of published datasets according to stipulated 12 loci MIRU-VNTR RDRio signatures revealed that 96.3% (129/134) of MDR and extensively drug resistant (XDR) clusters were RDRio. This is the first report associating the LAM RDRio sublineage with MDR. These results are an important contribution to the monitoring of these strains with heightened transmission for future endeavors to arrest MDR-TB and XDR-TB. (c) 2012 Elsevier B.V. All rights reserved.

Multidrug-resistant urinary tract isolates of Escherichia coli from Ribeirão Preto, São Paulo, Brazil

Multiple resistances to antimicrobial drugs arising in Escherichia coli isolates may complicate therapeutic management of urinary tract infection (UTI) by this organism. In order to assess the multidrug resistance (MDR) among urinary E. coli isolates, we have tested 11 antimicrobial drugs against 67 isolates from outpatients attended in a tertiary-care teaching hospital and of 78 isolates from a municipal health unit, respectively in Ribeirão Preto, State of São Paulo, Brazil. Seventy-six percent and 22% of the isolates from the tertiary-care hospital and the municipal unit, respectively, were resistant to three or more different classes of agents, and were considered to present MDR. Among the isolates from the hospital patients, 73.0%, 65.0%, 58.0%, 58.0% and 31.0% were resistant to tetracycline, ampicillin, cephalothin, trimethoprim-sulfamethoxazole (TMP/SMX) and norfloxacin, respectively; resistance from the municipal unit patients were 31.0%, 37.0%, 8.0%, 29.0% and 12.0% respectively, to the same drugs. The predominant phenotype among the MDR isolates presented is ampicillin, TMP/SMX and tetracycline resistance. The high prevalence of drug resistance among UTI patients calls for continuous surveillance to assure effective control of this infection. © 2007 by The Brazilian Journal of Infectious Diseases and Contexto Publishing. All rights reserved.

Colonization pressure and risk factors for acquisition of imipenem-resistant Acinetobacter baumannii in a medical surgical intensive care unit in Brazil

We studied a nonconcurrent cohort of 582 patients admitted to a medical-surgical intensive care unit. Use of antimicrobials (imipenem and metronidazole) was a risk factor for acquisition of imipenem-resistant Acinetobacter baumannii only for the subcohort of patients admitted in months in which colonization pressure was lower than the median value. © 2013 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.