Antimicrobial Drug Resistant Bacteria Research Articles

Changes in Ion Concentrations upon the Binding of Short Polyelectrolytes on Phospholipid Bilayers: Computer Study Addressing Interesting Physiological Consequences.

This computer study was inspired by the experimental observation of Y. Qian et al. published in ACS Applied Materials and Interfaces, 2018 that the short positively charged β-peptide chains and their oligomeric analogues efficiently suppress severe medical problems caused by antimicrobial drug-resistant bacteria despite them not penetrating the bacterial membrane. Our coarse-grained molecular dynamics (dissipative particle dynamics) simulations confirm the tentative explanation of the authors of the experimental study that the potent antimicrobial activity is a result of the entropically driven release of divalent ions (mainly magnesium ions essential for the proper biological function of bacteria) into bulk solution upon the electrostatic binding of β-peptides to the bacterial membrane. The study shows that in solutions containing cations Na+, Ca2+ and Mg2+, and anions Cl−, the divalent cations preferentially concentrate close to the membrane and neutralize the negative charge. Upon the addition of positively charged oligomer chains (models of β-peptides and their analogues), the oligomers electrostatically bind to the membrane replacing divalent ions, which are released into bulk solvent. Our simulations indicate that the entropy of small ions (which controls the behavior of synthetic polyelectrolyte solutions) plays an important role in this and also in other similar biologically important systems.

101. Impact of an Integrated Tele-Antimicrobial Stewardship Program at a Rural Community Hospital

BackgroundSmall hospitals in the US may lack access to infectious diseases (ID) expertise despite similar rates of antimicrobial use and drug-resistant bacteria as larger hospitals. A tele-antimicrobial stewardship program (TASP) is a force multiplier, expanding access to specialty care, training, and guidance on appropriate resource utilization. Data on the impact of TASPs in community or rural inpatient settings is limited.MethodsWe established a TASP at a 160-bed hospital in Armstrong County, PA (population < 5000) in September 2020. Tele-ID consult services were already being used (Figure 1). A non-local ID pharmacist or ID physician performed prospective audits and provided feedback with 1 local pharmacist on a 30-minute video conference call daily. At TASP implementation, all patients receiving intravenous (IV) fluoroquinolones, metronidazole, and azithromycin were reviewed. Figure 1 shows the additional support following TASP implementation, including addition of ceftriaxone, carbapenems, IV vancomycin, and tocilizumab to daily reviews. A patient monitoring form was developed to track interventions and the local pharmacists were trained in documentation. Table 1 lists other TASP features implemented.Figure 1. TASP Timeline Table 1. TASP Accomplishments ResultsFrom 09/01/2020 to 04/30/2021, 304 stewardship opportunities were identified and 77% of interventions were accepted. Recommending a duration of therapy was accepted most frequently (93.5%) and de-escalation of therapy least frequently (69.6%) (Table 2). Recommending an ID consultation or diagnostic testing was always accepted but only comprised 6.2% of all interventions. Daily calls involved an average of 5 patient reviews. Monthly antimicrobial use declined on average from 673 DOT (days of therapy)/1000 PD (patient days) to 638 DOT/1000 PD (Figure 2). Daily calls were cancelled on 31/166 weekdays (18.7%) due to staffing shortages.Table 2. TASP Interventions (9/2020 - 4/2021) Figure 2. Monthly Antimicrobial Use in Days of Therapy (DOT) per 1000 Patient Days (4/2019 - 5/2021) ConclusionImplementation of TASP in a community hospital resulted in a high percentage of accepted stewardship interventions and lower antimicrobial usage. Success is dependent on robust educational efforts, establishing strong relationships with local providers, and involvement of key stakeholders. Lack of dedicated stewardship time for local pharmacists is a very significant barrier.Disclosures Erin K. McCreary, PharmD, BCPS, BCIDP, AbbVie (Consultant)Cidara (Consultant)Entasis (Consultant)Ferring (Consultant)Infectious Disease Connect, Inc (Other Financial or Material Support, Director of Stewardship Innovation)Merck (Consultant)Shionogi (Consultant)Summit (Consultant) Erin K. McCreary, PharmD, BCPS, BCIDP, AbbVie (Individual(s) Involved: Self): Consultant; Cidara (Individual(s) Involved: Self): Consultant; Entasis (Individual(s) Involved: Self): Consultant; Ferring (Individual(s) Involved: Self): Consultant; Infectious Disease Connect, Inc (Individual(s) Involved: Self): Director of Stewardship Innovation, Other Financial or Material Support; Merck (Individual(s) Involved: Self): Consultant; Shionogi (Individual(s) Involved: Self): Consultant; Summit (Individual(s) Involved: Self): Consultant Tina Khadem, PharmD, Infectious Disease Connect, Inc. (Employee) Nancy Zimmerman, RN, BSN, I’d connect (Employee) John Mellors, MD, Abound Bio, Inc. (Shareholder)Accelevir (Consultant)Co-Crystal Pharma, Inc. (Other Financial or Material Support, Share Options)Gilead Sciences, Inc. (Advisor or Review Panel member, Research Grant or Support)Infectious DIseases Connect (Other Financial or Material Support, Share Options)Janssen (Consultant)Merck (Consultant) Rima Abdel-Massih, MD, Infectious Disease Connect (Employee, Director of Clinical Operations) Rima Abdel-Massih, MD, Infectious Disease Connect (Individual(s) Involved: Self): Chief Medical Officer, Other Financial or Material Support, Other Financial or Material Support, Shareholder J Ryan. Bariola, MD, Infectious Disease Connect (Other Financial or Material Support, salary support)

Prevalence of Methicillin Resistant Staphylococcus aureus in Raw Goat Milks from Selected Farms in Terengganu, Malaysia

The emergence of antimicrobial drug resistant bacteria has been a concern worldwide. One of bacteria that has been reported to develop resistance is Methicillin Resistant Staphylococcus aureus (MRSA). Recent studies showed that Livestock Associated MRSA (LA-MRSA) was found in domestic food animals and their handlers. The aim of this study was to investigate the prevalence of MRSA in goat milk of goat farms located in Terengganu. A total of 664 udder milks were taken from 332 goats at 40 selected farms within Terengganu state. Then, screening of bacteria and isolation of suspected S. aureus isolates in the milk samples was done using selective agar, Gram staining and biochemical tests. The identity of the bacteria isolated was further confirmed using PCR where specific designed primers were used to detect the presence of nuc gene of S. aureus (278bp) and mecA gene (533bp) of MRSA. Both S. aureus and MRSA isolates were also tested for their susceptibilities toward the antimicrobial drugs. Fifty milk samples were found to contain S. aureus and one of the S. aureus isolates were MRSA. The bacteria isolates were found to have higher tendency to be resistance toward Penicillin (26.0%) and Oxacillin (12.0%). This study provides useful data on the current status of MRSA prevalence in small ruminant’s milk, which can be used to prevent transmission of LA-MRSA to human and other animals.

Trend of Antimicrobial use and drug resistant bacteria and the comparison between our facility and 4 other facilities in Fukui Prefecture

Trend of Antimicrobial use and drug resistant bacteria and the comparison between our facility and 4 other facilities in Fukui Prefecture

Enteric Infections Circulating during Hajj Seasons, 2011-2013.

Hajj, the annual Muslim pilgrimage to Mecca, Saudi Arabia, is a unique mass gathering event that raises public health concerns in the host country and globally. Although gastroenteritis and diarrhea are common among Hajj pilgrims, the microbial etiologies of these infections are unknown. We collected 544 fecal samples from pilgrims with medically attended diarrheal illness from 40 countries during the 2011-2013 Hajj seasons and screened the samples for 16 pathogens commonly associated with diarrheal infections. Bacteria were the main agents detected, in 82.9% of the 228 positive samples, followed by viral (6.1%) and parasitic (5.3%) agents. Salmonella spp., Shigella/enteroinvasive Escherichia coli, and enterotoxigenic E. coli were the main pathogens associated with severe symptoms. We identified genes associated with resistance to third-generation cephalosporins ≈40% of Salmonella- and E. coli-positive samples. Hajj-associated foodborne infections pose a major public health risk through the emergence and transmission of antimicrobial drug-resistant bacteria.

Antimicrobial Activity of Citronella Essential Oil on Antimicro bial Drug Resistant Bacteria from Veterinary Clinical Cases

Study on citronella essential oil (CEO) sensitivity of 217 microbial strains of 65 species and isolated from animals with different disease conditions, revealed that citronella oil inhibited growth of only 10.6% strains. CEO inhibited Candida but of no Aspergillus strain. CEO inhibited 22 of 211 bacterial strains. Ampicillin was the least effective antibiotic and but inhibited 41.2% bacterial strains. Gram positive bacteria (GPBs) were 4.5 more sensitive (p, 0.0006) to CEO than Gram negative bacteria (GNBs). More GNB strains (p, 0.02) were multi-drug resistant (MDR) type than GPB strains. Probability of CEO resistant was high in MDR strains (p, 0.006). Most of the Brucella abortus strains had MDR (83.3%). Strains of swamp buffalo origin were more (p, 0.08) commonly CEO (96.6%) resistant than strains of dog (81.3%) origin. MDR was the maximum in abortion associated (51.2%) strains and minimum in diarrhoea associated strains (25%). The study indicated that CEO is not an effective antimicrobial against veterinary clinical isolates. Antimicrobial drug and CEO resistance patterns of bacteria were dependent on type of pathogen, its source and association with disease in animals and may be important for deciding an effective antimicrobial therapy.

Antimicrobial drug-resistant bacteria isolated from Syrian war-injured patients, August 2011-March 2013.

Antimicrobial drug-resistant bacteria isolated from Syrian war-injured patients, August 2011-March 2013.

Effect of preweaned dairy calf housing system on antimicrobial resistance in commensal Escherichia coli

Group housing of preweaned dairy calves is a growing practice in the United States. The objective of this practice is to increase the average daily gain of calves in a healthy and humane environment while reducing labor requirements. However, feeding protocols, commingling of calves, and occurrence of disease in different calf-housing systems may affect the prevalence of antimicrobial drug-resistant bacteria. This study evaluated the effect of a group pen-housing system and individual pen-housing system on antimicrobial resistance trends in fecal Escherichia coli of preweaned dairy calves and on the prevalence of environmental Salmonella. Twelve farms from central New York participated in the study: 6 farms using an individual pen-housing system (IP), and 6 farms using a group pen-housing system (GP). A maximum of 3 fecal E. coli isolates per calf was tested for susceptibility to 12 antimicrobial drugs using a Kirby-Bauer disk diffusion assay. Calves in GP had a significantly higher proportion of E. coli resistant to ciprofloxacin and nalidixic acid, whereas calves in IP had a significantly higher proportion of E. coli resistant to ampicillin, ceftiofur, gentamycin, streptomycin, and tetracycline. Calf-housing system had an effect on resistance to individual antimicrobial drugs in E. coli, but no clear-cut advantage to either system was noted with regard to overall resistance frequency. No outstanding difference in the richness and diversity of resistant phenotypes was observed between the 2 calf-housing systems.

Antibiotic susceptibility of infectious nosocomial microorganisms

Infectious diseases are the leading cause of death across the world. Evolution of antimicrobial drug resistant bacteria is a major health concern and extremely difficult to overcome. Nosocomial infections encompass all the clinical infections that do not originate from patients, originally admitting diagnosis. Critically ill patients have greater risk of developing nosocomial infections with resistant strains. Its incidence in developing nations is 5-10%. However, in India one in four patients admitted in hospital acquire nosocomial infections. These incidences are 4-5 times greater in general ward. In the present investigation strains of E. coli, Staphylococcus, Klebsiella, Enterobacter were isolated and identified based on morphological and biochemical tests, and were tested for their antibiotic susceptibilities. All the isolates were resistant to ampicillin and penicillin; however, they were sensitive to streptomycin, chloramphenicol and tetracycline. This study is an attempt to detect the presence of antibiotic sensitive / resistant pathogens in government hospital.

Analysis of antibacterial activity of nitrofurantoin from gram negative bacilli

Objective To understand the antibacterial activity of nitrofurantoin from gram negative bacilli,provide the basis for clinical rational use of furan appropriate for drugs.Methods Gram negative bacilli 5 589 strains isolated from clinical were monitored between January 2009 and December 2009.VITEK 2 Compact automatic bacteria identification instrument was used for bacteria identification and drug sensitive test.Whonet 5.6 software was used for data analysis.Results E.coli and klebsiella bacteria produced acid with nitrofurantoin had good antibacterial activity (resistance to ＜ 4.3%),E.coli and klebsiella pneumoniae to with nitrofurantoin for antimicrobial activity was good (the percentages of 25.6% ～ 25.6%),pseudomonas aeruginosa,acinetobacter baumannii,singular deformation bacteria and glue abdulrahman al saleh,bacterium antibacterial activity of furan appropriate for poorer(ni 93.7% ～ 98.9%).Imine resistance from south pseudomonas aeruginosa (IRPA),resistant to carbon penicillium alkene antimicrobial acinetobacter baumannii(CR-AB) and penicillium carbon alkene antimicrobial drug resistant enterobacteriaceae bacteria(CRE) with nitrofurantoin because of the percentages were 100.0% (108/108),100.0% (335/335) and 96.1% (74/77).Conclusion Urine,blood,pus,and secretion of primary separation of E.coli with nitrofurantoin has better antimicrobial activity; Sputum specimens of primary separation of pseudomonas aeruginosa and acinetobacter baumannii with nitrofurantoin has the high prevalence of resistance. Key words: Drug resistance ; Nitrofurantoin; Gram-negative bacteria

Antimicrobial Resistance: Beyond the Breakpoint

The Fifth Decennial International Conference on Healthcare-Associated Infections, held March 2010 in Atlanta, Georgia, USA, brought the issue of antimicrobial drug resistance to the forefront. Results of a survey that polled members of the Society for Healthcare Epidemiology of America regarding critical knowledge gaps and research priorities were presented. Respondents reported that 3 of the 5 most important issues they face are directly associated with antimicrobial drug resistance: multidrug–resistant gram-negative bacteria, antimicrobial stewardship, and methicillin-resistant Staphylococcus aureus (MRSA) The publication of this collection of authoritative reviews of these issues is therefore timely. This concise volume draws on the knowledge of 23 authors, many of whom are either current or past staff members of the Centers for Disease Control and Prevention. In 10 chapters and 174 pages, these authors address contemporary issues in bacterial, fungal, parasitic, and viral (HIV) resistance, as well as some aspects of the effects of antimicrobial drug resistance on healthcare facilities. The main emphasis of the book is on the epidemiology and mechanisms and public health implications of resistant pathogens, not on details of treatment. Chapters on MRSA, extended-spectrum β-lactamase–producing gram-negative bacteria, and fluoroquinolone resistance cover the epidemiology and mechanisms of resistance, laboratory detection, and treatment considerations. A historical review of the contribution of bacterial pneumonia to the death rate of previous influenza pandemics clearly discusses the likelihood and consequences of resistance in strains of Streptococcus pneumoniae and S. aureus. Questions raised here about how these antimicrobial drug–resistant bacteria affect a modern pandemic, such as the impact of antiviral drugs and diagnostic testing on antibiotic use, can now be investigated in light of the subsequent pandemic (H1N1) 2009. Three chapters address resistance in healthcare settings and the promotion of appropriate antimicrobial drug use. The first describes interventions to reduce the inappropriate use of antimicrobial agents for respiratory conditions and quality initiatives that can improve prescribing. The chapter that reviewed effective strategies for controlling resistant pathogens in hospitals is the only chapter that was not well referenced on some of the more controversial issues, such as silver coating of devices. However, the chapter on estimating costs attributable to infections caused by antimicrobial drug–resistant bacteria is comprehensive. Three final chapters expand the scope of this volume into issues of parasitic, fungal, and viral resistance. Resistance in helminths is presented in the context of mass treatment during eradication programs and the need for enhanced surveillance programs. The chapter on antifungal resistance reviews available drugs and laboratory detection of resistance. The final chapter on HIV drug resistance in the developing world reviews initial concerns and current encouraging data on antiretroviral drug–resistance in sub-Saharan Africa and southern Asia. Current public health strategies for detecting and controlling drug–resistant HIV are given, along with a clear account of the biological and pharmacologic factors that affect HIV resistance and a review of areas needing continued attention and resources. The strength of this book is the wide scope of its coverage of antimicrobial drug resistance. Most chapters are well written in a succinct style and format easily accessible to the general reader. The text has supportive references from primary sources, and contains a good index. This book is a valuable resource for those beginning their careers or who are looking for a research focus, or for anyone already an expert in an aspect of antimicrobial resistance who is seeking a broader perspective.

Vancomycin-Resistant Enterococci, Point Barrow, Alaska, USA

To the Editor: An increasing number of bacterial infections are now difficult or impossible to treat (1) because of the misuse of antimicrobial drugs and the epidemic spread of bacterial resistance to these drugs (2). The most alarming reports are of methicillin-resistant Staphylococcus aureus, extended-spectrum β-lactamase producers, and vancomycin-resistant enterococci (VRE). Although knowledge about dissemination mechanisms is poor, the spread of resistance clearly is not restricted to hospitals but occurs also in the community and in the natural environment (3,4). Since the 1990s, the epidemiology in the United States has shifted so that most VRE are Enterococcus faecium. Recent studies indicate clonal spread of the E. faecium CC17 lineage in clinical isolates, exhibiting high-level ampicillin and fluoroquinolone resistance and harboring an enterococcal surface protein–coding esp gene (5,6). During a polar research expedition to the Beringia region in 2005, we collected fecal samples from birds at sites with no or low human population. The aim was to investigate the current status of resistance dissemination into remote areas of the world. The study site in Alaska was located on the tundra halfway between the city of Barrow and Point Barrow, the northernmost point of the United States (71°23′20″N, 156°28′45″W). Fecal samples from glauocus gulls (Larus hyperboreus) were enriched (18 h at 37°C) in brain–heart infusion broth (Becton Dickinson, Franklin Lakes, NJ, USA) supplemented with aztreonam and vancomycin (10 mg/L and 4 mg/L, respectively; ICN Biomedicals Inc., Aurora, OH, USA), followed by spreading on chromID VRE plates (bioMerieux, Marcy l’Etoile, France) and incubated for 48 h at 37°C. Typical colonies were isolated and species identified by biochemical testing, including the Phoenix Automated Microbiology System (Becton Dickinson). MIC was determined for vancomycin, teicoplanin, ampicillin, and ciprofloxacin by using Etest strips (AB Biodisk, Solna, Sweden), and the presence of vanA, vanB, and esp genes was established by PCR with previously described primers (7,8) (esp primers esp11 and esp12). Cultures showed 2 isolates of E. faecium; MICs for vancomycin and teicoplanin were >256 and 96 µg/mL, respectively, for both isolates. Genotyping determined that they harbored vanA. Isolates exhibited high-level ampicillin and ciprofloxacin resistance; MICs were >256 and >32 µg mL, respectively for both isolates. They also harbored the esp gene. Isolates came from 2 of 33 sampled glaucous gulls, a species confined to the Arctic regions, that have limited southbound migration during the nonbreeding season. Clinical isolates of VRE were first found in the late 1980s. In the United States, vancomycin was widely used in human medicine, and outbreaks occurred in hospitals rather than in the community; the opposite was, and is, true in Europe. Because of massive use of glycopeptide antimicrobial drugs, i.e., avoparcin, as growth promoters in domestic animal production until the mid-1990s, VRE can be found in hospitals and the community (9). Our findings show that bacteria resistant to antimicrobial drugs, or resistance genes, already have spread to one of the most remote areas of North America, Point Barrow, Alaska. This spread suggests that few (if any) places on earth may be protected against the spread of such resistance, and the dispersal mechanisms are far more efficient than previously thought. Our data also place the isolates as part of the clinically spread clonal E. faecium CC17 lineage, characterized by high-level ampicillin and quinolone resistance and harboring the esp gene, thus strongly supporting a human origin. Possible dispersal mechanisms to remote areas include stepwise horizontal transfer between migratory and nonmigratory bird species and anthropogenic transport. The increasing evolution and spread of antimicrobial drug–resistant bacteria and resistance genes seriously threaten public health and could escalate to catastrophic proportions (1). Bacteria and drug resistance are easily transferred between humans and animals and consequently between the environment and clinical settings. Much remains to be learned about the effect of human-associated changes of natural ecosystems on the total effect of resistance. Therefore, our finding of VRE at Point Barrow is important to recognize. Decisive action is needed to establish efficient monitoring programs that include not only surveillance and control of clinical bacterial resistance but also environmental levels of resistance.

Subtherapeutic Antibiotics and Productivity in U.S. Hog Production

Antimicrobial drugs are fed to hogs at subtherapeutic levels to prevent disease and promote growth. However, there is concern that the presence of antimicrobial drugs in hog feed is a factor promoting the development of antimicrobial drug-resistant bacteria. This study uses a treatment-effects sample-selection model to examine the impact that feeding antibiotics has on the productivity of U.S. hog operations. No relationship was found between productivity and antibiotics fed during finishing, but productivity was significantly improved when antibiotics were fed to nursery pigs. Restrictions on feeding antimicrobial drugs during the nursery phase would likely impose significant economic costs on U.S. hog producers.

Antimicrobial Drug Use and Antibiotic-Resistant Bacteria

We appreciate the comments by Dr. Bellissimo-Rodrigues regarding our article analyzing risk factors for surveillance-culture positivity with extended-spectrum β-lactamase (ESBL)–producing bacteria (1). We agree with the author that patient-to-patient transmission is a potentially important causal factor in the emergence of resistance for ESBL-producing bacteria as well as for other antimicrobial drug–resistant bacteria, such as vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus, and drug-resistant Pseudomonas and Acinetobacter spp. For each of these resistant organisms, a complicated interplay likely exists between the causal importance of antibiotic selective pressure and patient-to-patient transmission by healthcare workers (2–4). The relative importance of these 2 causal mechanisms needs to be determined for each individual antimicrobial-resistant bacterium. The relative causal importance may be different for different outcomes: colonization on admission, colonization acquisition, and progression from colonization to infection. Understanding the relative importance for each of these outcomes is needed before determining whether infection control interventions or antimicrobial drug stewardship policies will be effective. For example, we have published work that demonstrates that patient-to-patient transmission is important for colonization acquisition of ESBL-producing Klebsiella spp. and Escherichia coli (5). We believe that a couple of points require clarification. In our article, we looked at risk factors for colonization with ESBL-producing bacteria on admission to an intensive care unit. We did not examine risk factors for selecting ESBL-producing bacteria as the letter implies. For the antimicrobial drugs identified as potential risk factors, we clearly stated in the discussion that the risk factors identified may be causally related to the outcome of ESBL-colonization or may only be statistically associated. We argue that even risk factors identified are not causal; they may be important because they can help determine which patients may need empiric antimicrobial drug therapy targeted to the ESBL-producing bacteria. Future research work is still needed to assess the relative importance of patient-to-patient transmission versus antimicrobial selective pressure.

ResistantSalmonellaVirchow in Quail Products

To the Editor: Salmonella spp. resistant to multiple antimicrobial agents have emerged worldwide in recent years, but clinical relevance varies with the agent to which resistance evolves. Fluoroquinolones are often the drug of choice to treat gastrointestinal infections in humans, and resistance to this class of antimicrobial agents is associated with increased illness and death (1). Resistance to fluoroquinolones has emerged worldwide during the last decade. Salmonella isolates resistant to oxyiminocephalosporins because they produce extended-spectrum β-lactamases (ESBLs) have emerged worldwide since 1992. This emergence has caused concern since cephalosporins are drugs of choice to treat salmonellosis in children, to whom fluoroquinolones must not be administered because of toxicity issues. In Denmark, the first ESBL-producing isolate of animal origin from a Salmonella enterica serovar Heidelberg isolated from a boar imported from Canada in 2003 was reported (2), but such isolates have not previously been reported in food products. On October 15, 2003, the Danish Institute for Veterinary Research, the national reference laboratory, received 3 Salmonella isolates found in quails imported from France. Salmonella isolates found at any importer's laboratory in Denmark are submitted to the reference laboratory for further analyses. The quails were in the importer's storage room at the time of sampling; sampling was performed routinely by the importer's own laboratory. At the reference laboratory, the isolates were serotyped as S. enterica serovar Virchow and found resistant to ampicillin, ceftiofur, cephalothin, nalidixic acid, and tetracycline and with reduced susceptibility to ciprofloxacin (MICs >0.125 μg/mL) (3). Polymerase chain reaction detection and sequencing (4) showed that the β-lactam resistance was mediated by blaCTX-M-9. Pulsed-field gel electrophoresis was performed by using XbaI and BlnI as restriction enzymes according to the PulseNet protocol (5), and all 3 isolates had the same profile. On October 23, the importer was informed of the laboratory's findings and the increased risk associated with salmonella isolates simultaneously resistant to quinolones and cephalosporins. Based on this information, the importer withdrew the product from the supermarkets on October 24. Recently, S. enterica Virchow with blaCTX-M-9 has also been reported in poultry, poultry products, and humans in France (6), as well as humans in Spain (7) and the United Kingdom (8). The isolates from France were also resistant to nalidixic acid; the isolates we have obtained from fresh quails imported from France are possibly related to these isolates. The global food-products trade is expected to increase in the future. Thus, attempts to improve food safety must emphasize detection of antimicrobial drug–resistant bacteria in imported food products. Furthermore, international agreements that limit contamination with drug-resistant bacteria and resistance genes at the primary production site are necessary to ensure consumer safety (9). International agreements must be based on antimicrobial-resistance data and early reports of emerging problems. Recently, the World Health Organization (WHO) launched the Global Salm Surv program (10) to isolate and identify antimicrobial resistance to Salmonella globally. Many national and international rules, as well as marketing and consumer factors, regulate the international trade of food products and live animals. Large international corporations may also affect international trade. For example, McDonald's Corporation has issued a global policy for antimicrobial drug use in food animals that specifies requirements for their food product suppliers. Local groceries or supermarkets may also impose their own standards nationally. We are aware of only 1 product withdrawal related to antimicrobial resistance, the quail imported from France. No international standards exist for managing food safety problems related to antimicrobial resistance. However, in 2003 the Food and Agriculture Organization of the United Nations, WHO, and the World Organisation for Animal Health jointly hosted a workshop with a panel of experts to scientifically assess resistance risks related to nonhuman use of antimicrobial drugs (9). The panel's purpose was also to provide recommendations to the Codex Alimentarius Commission for future risk management of antimicrobial drug resistance (9). Imposing restrictions on products with combinations of resistance, such as simultaneous resistance to quinolones and cephalosporins in Salmonella, as reported in this study, would be a good first step towards managing antimicrobial drug–resistance risks.

Antibacterial Cleaning Products and Drug Resistance

We examined whether household use of antibacterial cleaning and hygiene products is an emerging risk factor for carriage of antimicrobial drug-resistant bacteria on hands of household members. Households (N = 224) were randomized to use of antibacterial or nonantibacterial cleaning and hygiene products for 1 year. Logistic regression was used to assess the influence of antibacterial product use in homes. Antibacterial product use did not lead to a significant increase in antimicrobial drug resistance after 1 year (odds ratio 1.33, 95% confidence interval 0.74-2.41), nor did it have an effect on bacterial susceptibility to triclosan. However, more extensive and longer term use of triclosan might provide a suitable environment for emergence of resistant species. Further research on this issue is needed.

Role of calf-adapted Escherichia coli in maintenance of antimicrobial drug resistance in dairy calves.

The prevalence of antimicrobial drug-resistant bacteria is typically highest in younger animals, and prevalence is not necessarily related to recent use of antimicrobial drugs. In dairy cattle, we hypothesize that antimicrobial drug-resistant, neonate-adapted bacteria are responsible for the observed high frequencies of resistant Escherichia coli in calves. To explore this issue, we examined the age distribution of antimicrobial drug-resistant E. coli from Holstein cattle at a local dairy and conducted an experiment to determine if low doses of oxytetracycline affected the prevalence of antimicrobial drug-resistant E. coli. Isolates resistant to tetracycline (>4 microg/ml) were more prevalent in <3-month-old calves (79%) compared with lactating cows (14%). In an experimental trial where calves received diets supplemented with or without oxytetracycline, the prevalence of tetracycline-resistant E. coli was slightly higher for the latter group (P = 0.039), indicating that drug use was not required to maintain a high prevalence of resistant E. coli. The most common resistance pattern among calf E. coli isolates included resistance to streptomycin (>12 microg/ml), sulfadiazine (>512 microg/ml), and tetracycline (>4 microg/ml) (SSuT), and this resistance pattern was most prevalent during the period when calves were on milk diets. To determine if prevalence was a function of differential fitness, we orally inoculated animals with nalidixic acid-resistant strains of SSuT E. coli and susceptible E. coli. Shedding of SSuT E. coli was significantly greater than that of susceptible strains in neonatal calves (P < 0.001), whereas there was no difference in older animals (P = 0.5). These data support the hypothesis that active selection for traits linked to the SSuT phenotype are responsible for maintaining drug-resistant E. coli in this population of dairy calves.

Occurrence of antibiotic-resistant Escherichia coli isolated from environmental samples

A total of 311 E. coli strains were isolated from Sauce Chico River waters, and from Bahía Blanca estuary waters and sediments, Argentina. Resistance of organisms to seven antimicrobial drugs was assessed. Resistance was most common to streptomycin, sulphamide and tetracycline. The principal source of the antimicrobial drug-resistant bacteria was non-treated sewage. It is considered that the presence of antibiotic-resistant E. coli in the environment is a great problem, especially those carrying plasmids which might determine this capability (R factors). These plasmids can be transferred from resistant donors to certain sensitive recipients. It is well known that transference and selection may be the source of antibiotic resistance genes in bacterial population. On the other hand, the incidence of such tolerant bacteria is a good indicator of the environmental consequence of the antibiotic use for unnecessary purposes in human and animal medicine.

The effect of bambermycin, carbadox, chlortetracycline and olaquindox on antibiotic resistance in intestinal coliforms: A new animal model

Groups of germ-free mice kept in isolators and associated with faecal microflora from piglets were continuously given either water or a solution of one of the following: chlortetracycline (20 micrograms/ml), carbadox (50 micrograms/ml), olaquindox (50 micrograms/ml), bambermycin (flavomycin) (5 micrograms/ml) or mixtures of these drugs. The proportions of lactose-fermenting bacteria in their faeces which were resistant to chlortetracycline, carbadox or olaquindox were measured by a comparative plate-counting procedure. Compared to occurrence in control mice, the occurrence of antimicrobial drug-resistant bacteria was higher in mice receiving chlortetracycline (P less than 0.001) and lower in mice receiving bambermycins (P less than 0.005). In contrast, olaquindox and carbadox did not change the proportion of resistant coliforms in mice faeces. A control experiment was conducted with five groups of germ-free mice given the same flora and kept without drugs in separate isolators. No difference in the occurrence of resistant coliforms could be found between these groups. The germ-free mouse associated with faecal microflora from a conventional animal seems to be a suitable model for determining in vivo the effect of low doses of antimicrobial drugs on drug resistance in lactose-fermenting enteric flora.