Antimicrobial resistance in Swiss laying hens, prevalence and risk factors

Antimicrobial resistance is an emerging concern to public health, and food-producing animals are known to be a potential source for transmission of resistant bacteria to humans. As legislation of the European Union requires to ban conventional cages for the housing of laying hens on the one hand, and a high food safety standard for eggs on the other hand, further investigations about the occurrence of antimicrobial resistance in alternative housing types are required. In this study, we determined antimicrobial resistance in indicator bacteria from 396 cloacal swabs from 99 Swiss laying hen farms among four alternative housing types during a cross-sectional study. On each farm, four hens were sampled and exposure to potential risk factors was identified with a questionnaire. The minimal inhibitory concentration was determined using broth microdilution in Escherichia coli (n=371) for 18 antimicrobials and in Enterococcus faecalis (n=138) and Enterococcus faecium (n=153) for 16 antimicrobials. All antimicrobial classes recommended by the European Food Safety Authority for E. coli and enterococci were included in the resistance profile. Sixty per cent of the E. coli isolates were susceptible to all of the considered antimicrobials and 30% were resistant to at least two antimicrobials. In E. faecalis, 33% of the strains were susceptible to all tested antimicrobials and 40% were resistant to two or more antimicrobials, whereas in E. faecium these figures were 14% and 39% respectively. Risk factor analyses were carried out for bacteria species and antimicrobials with a prevalence of resistance between 15% and 85%. In these analyses, none of the considered housing and management factors showed a consistent association with the prevalence of resistance for more than two combinations of bacteria and antimicrobial. Therefore we conclude that the impact of the considered housing and management practices on the egg producing farms on resistance in laying hens is low.

Restricted use of glycopeptides in paediatric cancer patients with fever and neutropenia

Until now, studies confirming the safety of glycopeptide restriction in the empirical treatment of prolonged fever and neutropenia included only nine children. In an open-label observational study, the use of teicoplanin in paediatric oncology patients was investigated. A period of unrestricted use (2001-2003) was compared with a second period (2004) following implementation of a restrictive treatment guideline. Empirical first-line treatment consisted of piperacillin/tazobactam; in 2004, fosfomycin was added after 72 h as the second-line combination instead of teicoplanin. In total, 213 episodes (n=163 in 2001-2003; n=50 in 2004) managed with teicoplanin or fosfomycin (only 2004) were eligible. Empirical treatment of fever of unknown origin with teicoplanin was reduced by 97%. In 2004, the mean length of stay was 0.4 days shorter, no infection-related death occurred and no vancomycin-resistant enterococci were detected. Restriction of empirical glycopeptides is safe in paediatric cancer patients after first-line treatment with piperacillin/tazobactam. Fosfomycin appears to offer a feasible and cost-saving alternative in second-line combination therapy.

Influence of the developmental state of valvular lesions on the antimicrobial activity of cefotaxime in experimental enterococcal infections

Cefotaxime has little antimicrobial activity in vitro against most strains of enterococci, as measured by conventional MICs and MBCs. However, the MICs of cefotaxime against many enterococci are markedly reduced by the addition of serum to the test medium. To assess the relevance of this observation in vivo, we examined the efficacy of cefotaxime in experimental Streptococcus faecalis endocarditis. Since response to antimicrobial agents may vary with the degree of vegetation development, therapeutic efficacy was assessed both in rabbits with newly formed vegetations and in rabbits with well-developed endocardial lesions. Peak serum levels of cefotaxime (50.1 +/- 20.0 micrograms/ml) exceeded the MIC in medium supplemented with serum (4 micrograms/ml), but not in Mueller-Hinton broth alone (greater than 64 micrograms/ml). After 4 days of therapy, animals with newly formed lesions (therapy initiated 1 h after infection, transvalvular catheters removed) had lower mean vegetation bacterial titers than did untreated controls. Among animals with mature vegetations (therapy initiated 12 h after infection, catheters indwelling), the rate of mortality was significantly reduced by cefotaxime therapy. However, no difference in vegetation titers was observed. Thus, cefotaxime demonstrated antienterococcal activity within newly formed vegetations, but did not inhibit bacterial proliferation within well-established vegetations.

Molecular epidemiology and genetic linkage of macrolide and aminoglycoside resistance in Staphylococcus intermedius of canine origin

A collection of 77 Staphylococcus intermedius isolates from dogs and cats in Switzerland was examined for resistance to erythromycin. Resistance profiles for 14 additional antibiotics were compared between erythromycin-resistant and susceptible isolates. A resistance prevalence of 27% for erythromycin was observed in the population under study. Complete correlation between resistance to erythromycin, and to spiramycin, streptomycin, and neomycin was observed. The erythromycin-resistant isolates all had a reduced susceptibility to clindamycin when compared to the erythromycin-susceptible isolates. Both constitutive and inducible resistance phenotypes were observed for clindamycin. Ribotyping showed that macrolide-aminoglycoside resistance was randomly distributed among unrelated strains. This suggests that this particular resistance profile is not related to a single bacterial clone but to the horizontal transfer of resistance gene clusters in S. intermedius populations. The erythromycin-resistant isolates were all carrying erm(B), but not erm(A), erm(C), or msr(A). The erm(B) gene was physically linked to Tn5405-like elements known as resistance determinants for streptomycin, streptothricin, neomycin and kanamycin. Analysis of the region flanking erm(B) showed the presence of two different groups of erm(B)-Tn5405-like elements in the S. intermedius population examined and of elements found in Gram-positive species other than staphylococci. This strongly suggests that erm(B) or the whole erm(B)-Tn5405-like elements in S. intermedius originate from other bacterial species, possibly from enterococci.

Catheter removal versus retention in the management of catheter-associated enterococcal bloodstream infections

BACKGROUND Enterococci are an important cause of central venous catheter (CVC)-associated bloodstream infections (CA-BSI). It is unclear whether CVC removal is necessary to successfully manage enterococcal CA-BSI. METHODS A 12-month retrospective cohort study of adults with enterococcal CA-BSI was conducted at a tertiary care hospital; clinical, microbiological and outcome data were collected. RESULTS A total of 111 patients had an enterococcal CA-BSI. The median age was 58.2 years (range 21 to 94 years). There were 45 (40.5%) infections caused by Entercoccus faecalis (among which 10 [22%] were vancomycin resistant), 61 (55%) by Enterococcus faecium (57 [93%] vancomycin resistant) and five (4.5%) by other Enterococcus species. Patients were treated with linezolid (n=51 [46%]), vancomycin (n=37 [33%]), daptomycin (n=11 [10%]), ampicillin (n=2 [2%]) or quinupristin/dalfopristin (n=2 [2%]); seven (n=6%) patients did not receive adequate enterococcal treatment. Additionally, 24 (22%) patients received adjunctive gentamicin treatment. The CVC was retained in 29 (26.1%) patients. Patients with removed CVCs showed lower rates of in-hospital mortality (15 [18.3%] versus 11 [37.9]; P=0.03), but similar rates of recurrent bacteremia (nine [11.0%] versus two (7.0%); P=0.7) and a similar post-BSI length of hospital stay (median days [range]) (11.1 [1.7 to 63.1 days] versus 9.3 [1.9 to 31.8 days]; P=0.3). Catheter retention was an independent predictor of mortality (OR 3.34 [95% CI 1.21 to 9.26]). CONCLUSIONS To the authors' knowledge, the present article describes the largest enterococcal CA-BSI series to date. Mortality was increased among patients who had their catheter retained. Additional prospective studies are necessary to determine the optimal management of enterococcal CA-BSI.

Stricture of the Afferent Isoperistaltic Tubular Segment: A Late and Rare Cause of Bilateral Dilation of the Upper Urinary Tract After Ileal Bladder Substitution

OBJECTIVE To evaluate the etiology and treatment of bilateral hydronephrosis not responding to bladder substitute drainage after ileal bladder substitution using an afferent isoperistaltic tubular segment. MATERIALS AND METHODS A retrospective analysis was performed of a consecutive series of 739 patients who had undergone bladder substitution from April 1985 to August 2012. RESULTS Of the 739 ileal bladder substitute patients, 10 (1.4%) developed bilateral hydronephrosis unresponsive to complete bladder substitute drainage. The etiology was stenosis of the afferent isoperistaltic tubular segment. The median interval to presentation was 131 months (range 45-192). The incidence of afferent tubular segment stenosis was significantly higher in the 61 ileal bladder substitute patients with recurrent urinary tract infection (9 [15%]) than in the 678 without recurrent urinary tract infection (1 [0.15%]; P <.001). Urine cultures revealed mixed infections (34%), Escherichia coli (18%), Staphylococcus aureus (13%), enterococci (11%), Candida (8%), Klebsiella (8%), and others (8%). Seven patients underwent 10 endourologic interventions, only 1 of which was successful (10%). After failed endourologic treatment, 7 open surgical revisions with resection of the stricture were performed, with all 7 (100%) successful. CONCLUSION Bilateral dilation of the upper urinary tract after ileal orthotopic bladder substitution unresponsive to complete bladder substitute drainage is likely to be caused by stenosis of the afferent isoperistaltic tubular segment. The stenosis occurs almost exclusively in patients with long-lasting, recurrent urinary tract infection and can develop many years after the ileal bladder substitution. Minimally invasive endourologic treatment is usually unsuccessful; however, open surgical revision offers excellent results.

Vancomycin resistance has no influence on outcomes of enterococcal bacteriuria

Background Infections with vancomycin-resistant enterococci (VRE) are a growing concern in hospitals. The impact of vancomycin resistance in enterococcal urinary tract infection is not well-defined. Aim To describe the epidemiology of enterococcal bacteriuria in a hospital and compare the clinical picture and patient outcomes depending on vancomycin resistance. Methods This was a 6-month prospective cohort study of hospital patients who were admitted with or who developed enterococcal bacteriuria in a 1250-bed tertiary care hospital. We examined clinical presentation, diagnostic work-up, management, and outcomes. Findings We included 254 patients with enterococcal bacteriuria; 160 (63%) were female and median age was 65 years (range: 17–96). A total of 116 (46%) bacteriurias were hospital-acquired and 145 (57%) catheter-associated. Most patients presented with asymptomatic bacteriuria (ASB) (119; 47%) or pyelonephritis (64; 25%); 51 (20%) had unclassifiable bacteriuria and 20 (8%) had cystitis. Secondary bloodstream infection was detected in 8 (3%) patients. Seventy of 119 (59%) with ASB received antibiotics (mostly vancomycin). There were 74 (29%) VRE bacteriurias. VRE and vancomycin-susceptible enterococci (VSE) produced similar rates of pyelonephritis [19 (25%) vs 45 (25%); P = 0.2], cystitis, and ASB. Outcomes such as ICU transfer [10 (14%) VRE vs 17 (9%) VSE; P = 0.3], hospital length of stay (6.8 vs 5.0 days; P = 0.08), and mortality [10 (14%) vs 13 (7%); P = 0.1] did not vary with vancomycin susceptibility. Conclusions Vancomycin resistance did not affect the clinical presentation nor did it impact patient outcomes in this cohort of inpatients with enterococcal bacteriuria. Almost half of our cohort had enterococcal ASB; more than 50% of these asymptomatic patients received unnecessary antibiotics. Antimicrobial stewardship efforts should address overtreatment of enterococcal bacteriurias.

Impact of enterococcal colonization and infection in solid organ transplantation recipients from the Swiss Transplant Cohort Study

BACKGROUND: The burden of enterococcal infections has increased over the last decades with vancomycin-resistant enterococci (VRE) being a major health problem. Solid organ transplantation is considered as a risk factor. However, little is known about the relevance of enterococci in solid organ transplantation recipients in areas with a low VRE prevalence. METHODS: We examined the epidemiology of enterococcal events in patients followed in the Swiss Transplant Cohort Study between May 2008 and September 2011 and analyzed risk factors for infection, aminopenicillin resistance, treatment, and outcome. RESULTS: Of the 1234 patients, 255 (20.7%) suffered from 392 enterococcal events (185 [47.2%] infections, 205 [52.3%] colonizations, and 2 events with missing clinical information). Only 2 isolates were VRE. The highest infection rates were found early after liver transplantation (0.24/person-year) consisting in 58.6% of Enterococcus faecium. The highest colonization rates were documented in lung transplant recipients (0.33/person-year), with 46.5% E. faecium. Age, prophylaxis with a betalactam antibiotic, and liver transplantation were significantly associated with infection. Previous antibiotic treatment, intensive care unit stay, and lung transplantation were associated with aminopenicillin resistance. Only 4/205 (2%) colonization events led to an infection. Adequate treatment did not affect microbiological clearance rates. Overall mortality was 8%; no deaths were attributable to enterococcal events. CONCLUSIONS: Enterococcal colonizations and infections are frequent in transplant recipients. Progression from colonization to infection is rare. Therefore, antibiotic treatment should be used restrictively in colonization. No increased mortality because of enterococcal infection was noted

A Prospective Multicenter SPOG 2003 FN Study of Microbiologically Defined Infections in Pediatric Cancer Patients with Fever and Neutropenia.

BACKGROUND Fever and neutropenia (FN) often complicate anticancer treatment and can be caused by potentially fatal infections. Knowledge of pathogen distribution is paramount for optimal patient management. METHODS Microbiologically defined infections (MDI) in pediatric cancer patients presenting with FN by nonmyeloablative chemotherapy enrolled in a prospective multi-center study were analyzed. Effectiveness of empiric antibiotic therapy in FN episodes with bacteremia was assessed taking into consideration recently published treatment guidelines for pediatric patients with FN. RESULTS MDI were identified in a minority (22%) of pediatric cancer patients with FN. In patients with, compared to without MDI, fever (median, 5 [IQR 3-8] vs. 2 [IQR1-3] days, p < 0.001) and hospitalization (10 [6-14] vs. 5 [3-8] days, p < 0.001) lasted longer, transfer to the intensive care unit was more likely (13 of 95 [14%] vs. 7 of 346 [2.0%], p < 0.001), and antibiotics were given longer (10 [7-14] vs. 5 [4-7], p < 0.001). Empiric antibiotic therapy in FN episodes with bacteremia was highly effective if not only intrinsic and reported antimicrobial susceptibilities were considered but the purposeful omission of coverage for coagulase negative staphylococci and enterococci was also taken into account (81% [95%CI 68 - 90] vs. 96.6% [95%CI 87 - 99.4], p = 0.004) CONCLUSIONS: MDI were identified in a minority of FN episodes but they significantly affected management and the clinical course of pediatric cancer patients. Compliance with published guidelines was associated with effectiveness of empiric antibiotic therapy in FN episodes with bacteremia.

Role of milk and meat products as vehicles for antibiotic-resistant bacteria

This subject is reviewed under the following headings: Microbial contamination of raw meat and raw milk; Antibiotic resistance of food-borne pathogens; Antibiotic resistance of commensal and potentially pathogenic bacteria as a new threat in food microbiology; Antibiotic-resistant staphylococci in fermented meat and [in] milk products; Antibiotic-resistant Enterococcus sp. in fermented meat and [in] milk products; Enterococci in farm animals and meat; Enterococci in fermented food; Molecular characterization of resistance of food-borne enterococci; and Further ecological and epidemiological considerations of resistant live bacteria in food. It is concluded that further research is needed, particularly into the possible transfer of the resistance of bacteria consumed in meat or milk products to the indigenous bacteria of the human consumer.

Antibiotic resistance spread in food

Nutritive and therapeutic treatment of farm animals with antibiotics, amounting to half of the world's antibiotic output, has selected for resistant bacteria that may contaminate the food produced. Antibiotic-resistant enterococci and staphylococci from animals are found in food when they survive the production processes, as in raw cured sausages and raw milk cheeses1. The broad host ranges of some plasmids and the action of transposons in many bacteria allow antibiotic-resistance genes to be communicated by conjugation between different species and genera2,3. A multi-antibiotic resistance plasmid from a lactococcus found in cheese provides a historical record of such events.

Nosocomial infections in dialysis access.

Nosocomial infections in patients requiring renal replacement therapy have a high impact on morbidity and mortality. The most dangerous complication is bloodstream infection (BSI) associated with the vascular access, with a low BSI risk in arteriovenous fistulas or grafts and a comparatively high risk in central venous catheters. The single most important measure for preventing BSI is therefore the reduction of catheter use by means of early fistula formation. As this is not always feasible, prevention should focus on educational efforts, hand hygiene, surveillance of dialysis-associated events, and specific measures at and after the insertion of catheters. Core measures at the time of insertion include choosing the optimal site of insertion, the use of maximum sterile barrier precautions, adequate skin antisepsis, and the choice of catheter type; after insertion, access care needs to ensure hub disinfection and regular dressing changes. The application of antimicrobial locks is reserved for special situations. Evidence suggests that bundling a selection of the aforementioned measures can significantly reduce infection rates. The diagnosis of central line-associated BSI (CLABSI) is based on clinical signs and microbiological findings in blood cultures ideally drawn both peripherally and from the catheter. The prompt installation of empiric antibiotic treatment covering the most commonly encountered organisms is key regarding CLABSI treatment. Catheter removal is recommended in complicated cases or if cultures yield Staphylococcus aureus, enterococci, Pseudomonas or fungi. In other cases, guide wire exchange or catheter salvage strategies with antibiotic lock solutions may be acceptable alternatives.