Current crisis or artifact of surveillance: insights into rebound chlamydia rates from dynamic modelling

<p>Abstract</p> <p>Background</p> <p>After initially falling in the face of intensified control efforts, reported rates of sexually transmitted chlamydia in many developed countries are rising. Recent hypotheses for this phenomenon have broadly focused on improved case finding or an increase in the prevalence. Because of many complex interactions behind the spread of infectious diseases, dynamic models of infection transmission are an effective means to guide learning, and assess quantitative conjectures of epidemiological processes. The objective of this paper is to bring a unique and robust perspective to observed chlamydial patterns through analyzing surveillance data with mathematical models of infection transmission.</p> <p>Methods</p> <p>This study integrated 25-year testing volume data from the Canadian province of Saskatchewan with one susceptible-infected-treated-susceptible and three susceptible-infected-treated-removed compartmental models. Calibration of model parameters to fit observed 25-year case notification data, after being combined with testing records, placed constraints on model behaviour and allowed for an approximation of chlamydia prevalence to be estimated. Model predictions were compared to observed case notification trends, and extensive sensitivity analyses were performed to confirm the robustness of model results.</p> <p>Results</p> <p>Model predictions accurately mirrored historic chlamydial trends including an observed rebound in the mid 1990s. For all models examined, the results repeatedly highlighted that increased testing volumes, rather than changes in the sensitivity and specificity of testing technologies, sexual behaviour, or truncated immunological responses brought about by treatment can, explain the increase in observed chlamydia case notifications.</p> <p>Conclusions</p> <p>Our results highlight the significant impact testing volume can have on observed incidence rates, and that simple explanations for these observed increases appear to have been dismissed in favor of changes to the underlying prevalence. These simple methods not only demonstrate geographic portability, but the results reassure the public health effort towards monitoring and controlling chlamydia.</p

A unified framework of immunological and epidemiological dynamics for the spread of viral infections in a simple network-based population

<p>Abstract</p> <p>Background</p> <p>The desire to better understand the immuno-biology of infectious diseases as a broader ecological system has motivated the explicit representation of epidemiological processes as a function of immune system dynamics. While several recent and innovative contributions have explored unified models across cellular and organismal domains, and appear well-suited to describing particular aspects of intracellular pathogen infections, these existing immuno-epidemiological models lack representation of certain cellular components and immunological processes needed to adequately characterize the dynamics of some important epidemiological contexts. Here, we complement existing models by presenting an alternate framework of anti-viral immune responses within individual hosts and infection spread across a simple network-based population.</p> <p>Results</p> <p>Our compartmental formulation parsimoniously demonstrates a correlation between immune responsiveness, network connectivity, and the natural history of infection in a population. It suggests that an increased disparity between people's ability to respond to an infection, while maintaining an average immune responsiveness rate, may worsen the overall impact of an outbreak within a population. Additionally, varying an individual's network connectivity affects the rate with which the population-wide viral load accumulates, but has little impact on the asymptotic limit in which it approaches. Whilst the clearance of a pathogen in a population will lower viral loads in the short-term, the longer the time until re-infection, the more severe an outbreak is likely to be. Given the eventual likelihood of reinfection, the resulting long-run viral burden after elimination of an infection is negligible compared to the situation in which infection is persistent.</p> <p>Conclusion</p> <p>Future infectious disease research would benefit by striving to not only continue to understand the properties of an invading microbe, or the body's response to infections, but how these properties, jointly, affect the propagation of an infection throughout a population. These initial results offer a refinement to current immuno-epidemiological modelling methodology, and reinforce how coupling principles of immunology with epidemiology can provide insight into a multi-scaled description of an ecological system. Overall, we anticipate these results to as a further step towards articulating an integrated, more refined epidemiological theory of the reciprocal influences between host-pathogen interactions, epidemiological mixing, and disease spread.</p

Susceptibility of Pediococcus isolates to antimicrobial compounds in relation to hop-resistance and beer-spoilage

<p>Abstract</p> <p>Background</p> <p>Though important in the context of food microbiology and as potential pathogens in immuno-compromised humans, bacterial isolates belonging to the genus <it>Pediococcus </it>are best known for their association with contamination of ethanol fermentation processes (beer, wine, or fuel ethanol). Use of antimicrobial compounds (e.g., hop-compounds, Penicillin) by some industries to combat <it>Pediococcus </it>contaminants is long-standing, yet knowledge about the resistance of pediococci to antimicrobial agents is minimal. Here we examined <it>Pediococcus </it>isolates to determine whether antibiotic resistance is associated with resistance to hops, presence of genes known to correlate with beer spoilage, or with ability to grow in beer.</p> <p>Results</p> <p>Lactic acid bacteria susceptibility test broth medium (LSM) used in combination with commercially available GPN3F antimicrobial susceptibility plates was an effective method for assessing antimicrobial susceptibility of <it>Pediococcus </it>isolates. We report the finding of Vancomycin-susceptible <it>Pediococcus </it>isolates from four species. Interestingly, we found that hop-resistant, beer-spoilage, and beer-spoilage gene-harbouring isolates had a tendency to be more susceptible, rather than more resistant, to antimicrobial compounds.</p> <p>Conclusion</p> <p>Our findings indicate that the mechanisms involved in conferring hop-resistance or ability to spoil beer by <it>Pediococcus </it>isolates are not associated with resistance to antibiotics commonly used for treatment of human infections. Also, Vancomycin-resistance was found to be isolate-specific and not intrinsic to the genus as previously believed.</p

Activity of RX-04 Pyrrolocytosine Protein Synthesis Inhibitors against Multidrug-Resistant Gram-Negative Bacteria

Pyrrolocytosines RX-04A-D are designed to bind to the bacterial 50S ribosomal subunit differently from currently-used antibiotics. The four analogs had broad anti-Gram-negative activity: RX-04A inhibited 94.7% of clinical Enterobacteriaceae, Acinetobacter baumannii and Pseudomonas aeruginosa at 0.5-4 μg/ml, with no MICs >8 μg/ml. MICs for multi-resistant carbapenemase producers were up to two-fold higher than for control strains, with values ≥8 μg/ml for one Serratia isolate with porin and efflux lesions. mcr-1 did not affect MICs

In vitro activity of cefepime/zidebactam (WCK 5222) against Gram-negative bacteria

Background: Diazabicyclooctanes (DBOs) inhibit class A, class C and some class D β-lactamases. A few also bind PBP2, conferring direct antibacterial activity and a β-lactamase-independent ‘enhancer' effect, potentiating β-lactams targeting PBP3. We tested a novel DBO, zidebactam, combined with cefepime. Methods: CLSI agar dilution MICs were determined with cefepime/zidebactam in a chequerboard format. Bactericidal activity was also measured. Results: Zidebactam MICs were ≤2 mg/L (mostly 0.12–0.5 mg/L) for most Escherichia coli, Klebsiella, Citrobacter and Enterobacter spp., but were >32 mg/L for Proteeae, most Serratia and a few E. coli, Klebsiella and Enterobacter/Citrobacter. The antibacterial activity of zidebactam dominated chequerboard studies for Enterobacteriaceae, but potentiation of cefepime was apparent for zidebactam-resistant isolates with class A and C enzymes, illustrating β-lactamase inhibition. Overall, cefepime/zidebactam inhibited almost all Enterobacteriaceae with AmpC, ESBL, K1, KPC and OXA-48-like β-lactamases at 1 + 1 mg/L and also 29 of 35 isolates with metallo-carbapenemases, including several resistant to zidebactam alone. Zidebactam MICs for 36 of 50 Pseudomonas aeruginosa were 4–16 mg/L, and the majority of AmpC, metallo-β-lactamase-producing and cystic fibrosis isolates were susceptible to cefepime/zidebactam at 8 + 8 mg/L. Zidebactam MICs for Acinetobacter baumannii and Stenotrophomonas maltophilia were >32 mg/L; potentiation of cefepime was frequent for S. maltophilia, but minimal for A. baumannii. Kill curve results largely supported MICs. Conclusion: Zidebactam represents a second triple-action DBO following RG6080, with lower MICs for Enterobacteriaceae and P. aeruginosa. Clinical evaluation of cefepime/zidebactam must critically evaluate the reliance that can be placed on this direct antibacterial activity and on the enhancer effect as well as β-lactamase inhibition

Sensitivity of a subregional scale atmospheric inverse CO 2 modeling framework to boundary conditions

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95175/1/jgrd16614.pd

Atmospheric inverse modeling to constrain regional‐scale CO 2 budgets at high spatial and temporal resolution

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95480/1/jgrd15697.pd

WCK 4234, a novel diazabicyclooctane potentiating carbapenems against Enterobacteriaceae, Pseudomonas and Acinetobacter with class A, C and D β-lactamases

Background: Several diazabicyclooctanes (DBOs) are under development as inhibitors of Class A and C -lactamases. Inhibition of OXA (Class D) carbapenemases is variable, with those of Acinetobacter spp. remaining notably resistant. We describe a novel DBO, WCK 4234 (Wockhardt), with distinctive activity against OXA carbapenemases.  Methods: MICs of imipenem and meropenem were determined by CLSI agar dilution with WCK 4234 added at 4 or 8 mg/L. Test organisms were clinical Enterobacteriaceae, Acinetobacter baumannii and Pseudomonas aeruginosa with carbapenemases or carbapenem resistance via porin loss plus AmpC or ESBL activity. AmpC mutants were also tested.  Results: WCK 4234, which lacked direct antibacterial activity, strongly potentiated imipenem and meropenem against Enterobacteriaceae with OXA-48/181, KPC enzymes, or with combinations of impermeability and AmpC or ESBL activity, with MICs reduced to <2 mg/L in almost all cases. Carbapenems likewise were potentiated against P. aeruginosa (n=2) with OXA-181 enzyme, with MICs reduced from 64-128 mg/L to 2-8 mg/L and against A. baumannii with OXA carbapenemases, particularly OXA-23 or hyperproduced OXA-51, with MICs reduced to <2 mg/L for 9/10 acinetobacters with OXA-23 enzyme. Carbapenems were not potentiated against Enterobacteriaceae or non-fermenters with metallo--lactamases.   Conclusion: WCK 4234 distinctively overcame resistance mediated by OXA-type carbapenemases, including in A. baumannii. It behaved similarly to other DBOs against strains with KPC carbapenemases or combinations of impermeability and ESBL or AmpC activity

Towards practice-based studies of HRM: an actor-network and communities of practice informed approach

HRM may have become co-terminus with the new managerialism in the rhetorical orthodoxies of the HRM textbooks and other platforms for its professional claims. However, we have detailed case-study data showing that HR practices can be much more complicated, nuanced and indeed resistive toward management within organizational settings. Our study is based on ethnographic research, informed by actor-network theory and community of practice theory conducted by one of the authors over an 18-month period. Using actor-network theory in a descriptive and critical way, we analyse practices of managerial resistance, enrolment and counter-enrolment through which an unofficial network of managers used a formal HRM practice to successfully counteract the official strategy of the firm, which was to close parts of a production site. As a consequence, this network of middle managers effectively changed top management strategy and did so through official HRM practices, coupled with other actor-network building processes, arguably for the ultimate benefit of the organization, though against the initial views of the top management. The research reported here, may be characterized as a situated study of HRM-in-practice and we draw conclusions which problematize the concept of HRM in contemporary management literature