Antibiotic-susceptible Bacteria Research Articles

Quantitative Microbial Risk Assessment of Antibiotic-Resistant E. coli, Legionella pneumophila, and Mycobacteria in Nonpotable Wastewater Reuse Applications.

Antibiotic-resistant bacteria (ARB) have become a major threat to public health and modern medicine. A simple death kinetics-based dose-response model (SD-DRM) was incorporated into a quantitative microbial risk assessment (QMRA) to assess the risks of exposure to reclaimed wastewater harboring antibiotic-resistant E. coli, Legionella pneumophila, and Mycobacterium avium for multiple exposure scenarios. The fractions of ARB and trace antibiotics present in the body were incorporated to demonstrate their impact on infection risks. Both ARB and antibiotic susceptible bacteria, ASB, are assumed to have the same dose-response in the absence of antibiotics but behave differently in the presence of residual antibiotics in the body. Annual risk of L. pneumophila infection exceeded the EPA 10-4 pppy (per person per year) benchmark at concentrations in reclaimed water greater than 103-104 CFU/L, depending on parameter variation. Enteropathogenic E. coli infection risks meet the EPA annual benchmark at concentrations around 105-106 total E. coli. The results illustrated that an increase in residual antibiotics from 0 to 40% of the minimum inhibitory concentration (MIC) reduced the risk by about 1 order of magnitude for E. coli but was more likely to result in an untreatable infection.

Assessment of antibiotic-resistant infection risks associated with reclaimed wastewater irrigation in intensive tomato cultivation

Agricultural irrigation using reclaimed urban wastewater (RWW) represents a sustainable practice to meet the ever-increasing water stress in modern societies. However, the occurrence of residual antibiotics and antibiotic resistant bacteria (ARB) in RWW is an important human health concern. This study applied for the first time a novel Simple-Death dose-response model to the field data of Escherichia coli and Pseudomonas spp. collected from three greenhouses for cultivation of tomatoes irrigated with RWW. The model estimates the risk of infection by enteropathogenic E. coli associated with consumption of tomatoes and the risk of eye-infection caused by Pseudomonas aeruginosa in cultivation soil through hand-to-eye contacts. The fraction of antibiotic resistant (AR)-E. coli measured in irrigation water and AR-Pseudomonas spp. in soil was incorporated in the model to estimate the survival of ARB and antibiotic susceptible bacteria in the presence of trace level of antibiotics in human body. The results showed that the risk of E. coli infection through consumption of tomatoes irrigated with RWW is within the WHO and USEPA recommended risk threshold (<10−4); Pseudomonas aeruginosa eye-infection risk is at or below the acceptable risk level. The presence of residual antibiotic in human body reduced the overall risk probabilities of infections but selectively enhanced the survival of ARB in comparison to their susceptible counterparts, which resulted in antibiotic untreatable infection. Therefore, the outcomes of this study call for a new risk threshold for antibiotic untreatable infections and highlight the key importance of adopting work safety measures for better human health protection.

ESBL- Escherichia coli extracellular vesicles mediate bacterial resistance to β-lactam and mediate horizontal transfer of blaCTX-M-55

Extracellular vesicles (EVs) have become the focus of research as an emerging method of horizontal gene transfer. In recent years, studies on the association between EVs and the spread of bacterial resistance have emerged, but there is a lack of research on the role of EVs secreted by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli in the spread of β-lactam resistance. Therefore, the aim of this study was to investigate the role of EVs in the transmission of β-lactam resistance. In this study, the role of EVs in the transmission of β-lactam resistance in E. coli was evaluated by the EVs-mediated bacterial resistance to β-lactam antibiotics test and the EVs-mediated blaCTX-M-55 transfer experiments using EVs secreted by ESBL-E. coli. The results showed that ESBL-EVs were protective against β-lactam antibiotic-susceptible bacteria, and this protective effect was dependent on the integrity of the EVs and showed dose- and time-dependent effects. At the same time, ESBL-EVs can also mediate the horizontal transmission of blaCTX-M-55, and EVs-mediated gene transfer is selective, preferring to transfer in more closely related species. In this study, we demonstrated the important role of EVs in the transmission of β-lactam resistance in chicken ESBL-E. coli, and evaluated the risk of EVs-mediated horizontal gene transfer, which provided a theoretical basis for elucidating the mechanism of EVs-mediated resistance transmission.

Isolation and Identification of Antibiotic-Susceptible Bacteria from Abattoir Effluent in Port Harcourt, Rivers State, Nigeria

Abattoir environment can become a significant reservoir for antibiotic resistance bacteria, particularly in abattoirs that do not treat their waste before discharge. This study seeks to verify the antibiotics susceptibility profile of bacteria isolated from abattoir wastewater in Port Harcourt, River State, Nigeria. The bacteria were isolated from the wastewater using a standard plating technique. The antibiotics sensitivity pattern of all bacterial isolates was determined by the Kirby-Bauer disk diffusion method. Isolates with high multiple antibiotic resistance (MAR) index (≥0.5) were screened for genes for pathogenicity (icaC, adhesion gene) and antibiotic resistance (QnrA gene). The abattoir wastewaters were contaminated by bacteria resistant to no less than two of the antibiotics experimented with (MAR index range, 0.2-1.0). The isolates were identified as Acinetobacter brisouii, Bacillus altitudinis, Bacillus stratosphericus and Priestia flexa. Among these isolates, 2(50.0%) harboured the QnrA gene while 3(75.0%) harboured the icaC gene. The findings underscore the importance of abattoir wastewater as an environmental flashpoint for antibiotic resistance. Detection of bacteria with multiple antibiotic resistance in abattoir wastewater would inform cautious use of antibiotics, to check the spread of antibiotic resistance emanating from this source.

Machine learning-based impedance system for real-time recognition of antibiotic-susceptible bacteria with parallel cytometry

Impedance cytometry has enabled label-free and fast antibiotic susceptibility testing of bacterial single cells. Here, a machine learning-based impedance system is provided to score the phenotypic response of bacterial single cells to antibiotic treatment, with a high throughput of more than one thousand cells per min. In contrast to other impedance systems, an online training method on reference particles is provided, as the parallel impedance cytometry can distinguish reference particles from target particles, and label reference and target particles as the training and test set, respectively, in real time. Experiments with polystyrene beads of two different sizes (3 and 4.5 µm) confirm the functionality and stability of the system. Additionally, antibiotic-treated Escherichia coli cells are measured every two hours during the six-hour drug treatment. All results successfully show the capability of real-time characterizing the change in dielectric properties of individual cells, recognizing single susceptible cells, as well as analyzing the proportion of susceptible cells within heterogeneous populations in real time. As the intelligent impedance system can perform all impedance-based characterization and recognition of particles in real time, it can free operators from the post-processing and data interpretation.

Membrane vesicles from antibiotic-resistant Staphylococcus aureus transfer antibiotic-resistance to antibiotic-susceptible Escherichia coli.

AimBacteria naturally produce membrane vesicles (MVs), which have been shown to contribute to the spread of multi‐drug resistant bacteria (MDR) by delivering antibiotic‐resistant substances to antibiotic‐susceptible bacteria. Here, we aim to show that MVs from Gram‐positive bacteria are capable of transferring β‐lactam antibiotic‐resistant substances to antibiotic‐sensitive Gram‐negative bacteria.Materials and MethodsMVs were collected from a methicillin‐resistant strain of Staphylococcus aureus (MRSA) and vesicle‐mediated fusion with antimicrobial‐sensitive Escherichia coli (RC85). It was performed by exposing the bacteria to the MVs to develop antimicrobial‐resistant E. coli (RC85‐T).ResultsThe RC85‐T exhibited a higher resistance to β‐lactam antibiotics compared to the parent strain. Although the secretion rates of the MVs from RC85‐T and the parent strain were nearly equal, the β‐lactamase activity of the MVs from RC85‐T was 12‐times higher than that of MVs from the parent strain, based on equivalent protein concentrations. Moreover, MVs secreted by RC85‐T were able to protect β‐lactam‐susceptible E. coli from β‐lactam antibiotic‐induced growth inhibition in a dose‐dependent manner.ConclusionMVs play a role in transferring substances from Gram‐positive to Gram‐negative bacteria, shown by the release of MVs from RC85‐T that were able to protect β‐lactam‐susceptible bacteria from β‐lactam antibiotics.Significance and impact of studyMVs are involved in the emergence of antibiotic‐resistant strains in a mixed bacterial culture, helping us to understand how the spread of multidrug‐resistant bacteria could be reduced.

Does plasmid-based beta-lactam resistance increase E. coli infections: Modelling addition and replacement mechanisms

Infections caused by antibiotic-resistant bacteria have become more prevalent during past decades. Yet, it is unknown whether such infections occur in addition to infections with antibiotic-susceptible bacteria, thereby increasing the incidence of infections, or whether they replace such infections, leaving the total incidence unaffected. Observational longitudinal studies cannot separate both mechanisms. Using plasmid-based beta-lactam resistant E. coli as example we applied mathematical modelling to investigate whether seven biological mechanisms would lead to replacement or addition of infections. We use a mathematical neutral null model of individuals colonized with susceptible and/or resistant E. coli, with two mechanisms implying a fitness cost, i.e., increased clearance and decreased growth of resistant strains, and five mechanisms benefitting resistance, i.e., 1) increased virulence, 2) increased transmission, 3) decreased clearance of resistant strains, 4) increased rate of horizontal plasmid transfer, and 5) increased clearance of susceptible E. coli due to antibiotics. Each mechanism is modelled separately to estimate addition to or replacement of antibiotic-susceptible infections. Fitness costs cause resistant strains to die out if other strain characteristics are maintained equal. Under the assumptions tested, increased virulence is the only mechanism that increases the total number of infections. Other benefits of resistance lead to replacement of susceptible infections without changing the total number of infections. As there is no biological evidence that plasmid-based beta-lactam resistance increases virulence, these findings suggest that the burden of disease is determined by attributable effects of resistance rather than by an increase in the number of infections.

Antibiotics for lower respiratory tract infection in children presenting in primary care (ARTIC-PC): the predictive value of molecular testing

ObjectivesThis study aimed to assess whether the presence of bacteria or viruses in the upper airway of children presenting with uncomplicated lower respiratory tract infection (LRTI) predicts the benefit of antibiotics. MethodsChildren between 6 months and 12 years presenting to UK general practices with an acute LRTI were randomized to receive amoxicillin 50 mg/kg/d for 7 days or placebo. Children not randomized (ineligible or clinician/parental choice) could participate in a parallel observational study. The primary outcome was the duration of symptoms rated moderately bad or worse. Throat swabs were taken and analyzed for the presence of bacteria and viruses by multiplex PCR. ResultsSwab results were available for most participants in the trial (306 of 432; 71%) and in the observational (182 of 326; 59%) studies. Bacterial pathogens potentially sensitive to amoxicillin (Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae) were detected among 51% of the trial placebo group and 49% of the trial antibiotic group. The median difference in the duration of symptoms rated moderately bad or worse between antibiotic and placebo was similar when potentially antibiotic-susceptible bacteria were present (median: –1 day; 99% CI, –12.3 to 10.3) or not present (median: –1 day; 99% CI, –4.5 to 2.5). Furthermore, bacterial genome copy number did not predict benefit. There were similar findings for all secondary outcomes and when including the data from the observational study. DiscussionThere was no clear evidence that antibiotics improved clinical outcomes conditional on the presence or concentration of bacteria or viruses in the upper airway. Before deploying microbiologic point-of-care tests for children with uncomplicated LRTI in primary care, rigorous validating trials are needed.

Bacterial persistence is essential for susceptible cell survival in indirect resistance, mainly for lower cell densities.

Antibiotic-susceptible bacteria may survive bactericidal antibiotics if other co-inhabiting bacteria detoxify the medium through antibiotic degradation or modification, a phenomenon denominated as indirect resistance. However, it is unclear how susceptible cells survive while the medium is still toxic. One explanation relies on the speed of detoxification, and another, non-exclusive explanation, relies on persistence, a state of bacterial dormancy where cells with low metabolic activity and growth rates are phenotypically tolerant to antibiotics and other cytotoxic substances. Here we simulated the fate of susceptible cells in laboratory experiments in the context of indirect resistance to understand whether persistence is necessary to explain the survival of susceptible cells. Depending on the strain and experimental conditions, the decay of persister populations may follow an exponential or a power-law distribution. Therefore, we studied the impact of both distributions in the simulations. Moreover, we studied the impact of considering that persister cells have a mechanism to sense the presence of a toxic substance–a mechanism that would enable cells to leave the dormant state when the medium becomes nontoxic. The simulations show that surviving susceptible cells under indirect resistance may originate both from persister and non-persister populations if the density of detoxifying cells is high. However, persistence was necessary when the initial density of detoxifying cells was low, although persister cells remained in that dormancy state for just a few hours. Finally, the results of our simulations are consistent both with exponential and power-law decay of the persistence population. Whether indirect resistance involves persistence should impact antibiotic treatments.

Occurrence of high-risk mcr-1 gene and blaNDM-1 positive superbug in the reverse osmosis filter cartridges of the household water purifiers

Household water purifiers (HWPs) are increasingly used to clean water at home, representing the last defense of chemical and microbial contaminants in drinking water. However, little is known about antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) in the HWPs. Here, we quantified ARB and ARGs on the reverse osmosis (RO) membranes of the HWPs using both culture-dependent and independent approaches. 84 ARGs conferring resistance to 11 antibiotics through three major mechanisms of antibiotic deactivation, efflux, and cellular protection were detected. For the first time, we found high-risk mcr-1, blaIMP, and blaVIM genes in some RO cartridges, which can confer bacterial resistance to the last-resort antibiotics colistin and carbapenems. Furthermore, 27 antibiotic-resistant opportunistic human pathogens were isolated from the RO filters, including a particularly dangerous blaNDM-1 carrying superbug that can transfer blaNDM-1 to the antibiotic susceptible bacteria by conjugation in the laboratory. The potential ARG horizontal transfer on the RO filter was also proposed. Overall, this study characterizes the RO filter-associated ARB and ARGs in HWPs and highlights their potential contaminations in drinking water.

Synthesis and characterization of novel chelation-free Zn(II)-azole complexes: Evaluation of antibacterial, antioxidant, and DNA binding activity

Here, we have synthesized novel chelation-free Zn(II)-complexes (1-3) [ZnCl2L2] of monodentate ligands with L= 2-isopropylimidazole (L1), 2-methylbenzimidazole (L2), and 2-methylbenzoxazole (L3) and evaluated their antibacterial, antioxidant and DNA binding activities. The chelation-free properties of these coordination complexes were confirmed by UV-Vis spectroscopy, 1H-NMR spectroscopy, single X-ray crystallography, and elemental analysis. Complexes 1-3 exhibited substantial antibacterial activity against all antibiotic susceptible bacteria within a concentration range of 100-200 µg/ml while free ligands L1 and L2 exhibited weak antibacterial activity considerably concentration above 200 µg/ml. Also, both complexes 2 and 3 were twice more active against methicillin-resistant staphylococcus aureus (MRSA) than complex 1. Furthermore, we found that complexes 1-3 showed DNA binding activity with E. coli plasmid DNA (pDNA) and calf thymus DNA (CT-DNA), which may be a plausible mechanism for their antibacterial activity. We also investigated the antioxidant activity of complexes 1-3 and found that complex 2 exhibited potential antioxidant activity compared to complexes 1 and 3. All these results suggest that the chelation-free Zn(II)-complexes can be the future candidates for more advanced biological studies.

A dose response model for quantifying the infection risk of antibiotic-resistant bacteria

Quantifying the human health risk of microbial infection helps inform regulatory policies concerning pathogens, and the associated public health measures. Estimating the infection risk requires knowledge of the probability of a person being infected by a given quantity of pathogens, and this relationship is modeled using pathogen specific dose response models (DRMs). However, risk quantification for antibiotic-resistant bacteria (ARB) has been hindered by the absence of suitable DRMs for ARB. A new approach to DRMs is introduced to capture ARB and antibiotic-susceptible bacteria (ASB) dynamics as a stochastic simple death (SD) process. By bridging SD with data from bench experiments, we demonstrate methods to (1) account for the effect of antibiotic concentrations and horizontal gene transfer on risk; (2) compute total risk for samples containing multiple bacterial types (e.g., ASB, ARB); and (3) predict if illness is treatable with antibiotics. We present a case study of exposure to a mixed population of Gentamicin-susceptible and resistant Escherichia coli and predict the health outcomes for varying Gentamicin concentrations. Thus, this research establishes a new framework to quantify the risk posed by ARB and antibiotics.

More microbiome–human health connections found

This year scientists continued to unravel the complicated ties between human health and the thousands of microbial strains living on and inside our bodies. These microbes have evolved with humans for millennia and have been considered benign, if not helpful, to us. But as researchers at the University of Sheffield discovered, that’s not always the case. The team found that a noninfectious strain of skin bacteria called Micrococcus luteus promotes development of pathogenic Staphylococcus aureus infections in mice (Nat. Microbiol. 2018, DOI: 10.1038/s41564-018-0198-3). What’s most interesting, says Trinity College Dublin’s Rachel M. McLoughlin, who wasn’t involved in the study, is that even dead M. luteus cells promoted infection, which means that dying, antibiotic-susceptible bacteria may actually help antibiotic-resistant bacteria survive. M. luteus’s betrayal aside, many bacteria strains are still beneficial, especially in the gut. Several studies showed that disrupting this microbial community could have negative effects on our health. One

Expanding the Current Knowledge About the Role of Interleukin-10 to Major Concerning Bacteria.

Interleukin-10 (IL-10) is one of the most important anti-inflammatory cytokine produced during bacterial infection. Two related phenomena explain the importance of IL-10 production in this context: first, the wide range of cells able to produce this cytokine and second, the wide effects that it causes on target cells. In a previous report we described opposing roles of IL-10 production during bacterial infection. Overall, during infections caused by intracellular bacteria or by pathogens that modulate the inflammatory response, IL-10 production facilitates bacterial persistence and dissemination within the host. Whereas during infections caused by extracellular or highly inflammatory bacteria, IL-10 production reduces host tissue damage and facilitates host survival. Given that these data were obtained using antibiotic susceptible bacteria, the potential application of these studies to multi-drug resistant (MDR) bacteria needs to be evaluated. MDR bacteria can become by 2050 a major death cause worldwide, not only for its ability to resist antimicrobial therapy but also because the virulence of these strains is different as compared to antibiotic susceptible strains. Therefore, it is important to understand the interaction of MDR-bacteria with the immune system during infection. This review discusses the current data about the role of IL-10 during infections caused by major circulating antibiotic resistant bacteria. We conclude that the production of IL-10 improves host survival during infections caused by extracellular or highly inflammatory bacteria, however, it is detrimental during infections caused by intracellular bacteria or bacterial pathogens that modulate the inflammatory response. Importantly, during MDR-bacterial infections a differential IL-10 production has been described, compared to non-MDR bacteria, which might be due to virulence factors specific of MDR bacteria that modulate production of IL-10. This knowledge is important for the development of new therapies against infections caused by these bacteria, where antibiotics effectiveness is dramatically decreasing.

Outer membrane vesicles from \u03b2-lactam-resistant Escherichia coli enable the survival of \u03b2-lactam-susceptible E. coli in the presence of \u03b2-lactam antibiotics

Outer membrane vesicles (OMVs) containing various bacterial compounds are released from mainly gram-negative bacteria. Secreted OMVs play important roles in the ability of a bacterium to defend itself, and thus contribute to the survival of bacteria in a community. In this study, we collected OMVs from β-lactam antibiotic-resistant Escherichia coli established by conjugation assay and the parental β-lactam antibiotic-susceptible strain, and performed comparative proteomic analysis to examine whether these OMVs carried β-lactam-resistant compounds. We also investigated whether both types of OMVs could protect susceptible cells from β-lactam-induced death and/or directly degrade β-lactam antibiotics. Several proteins that can be involved in degrading β-lactam antibiotics were more abundant in OMVs from β-lactam-resistant E. coli, and thus OMVs from β-lactam resistant E. coli could directly and dose-dependently degrade β-lactam antibiotics and fully rescue β-lactam-susceptible E. coli and other bacterial species from β-lactam antibiotic-induced growth inhibition. Taken together, present study demonstrate that OMVs from β-lactam-resistant E. coli play important roles in survival of antibiotic susceptible bacteria against β-lactam antibiotics. This finding may pave the way for new efforts to combat the current global spread of antibiotic resistances, which is considered to be a significant public health threat.

Rapid Assessment of Resistance to Antibiotic Inhibitors of Protein Synthesis in the Gram-Positive Pathogens, Enterococcus faecalis and Streptococcus pneumoniae, Based on Evaluation of the Lytic Response.

A novel assay for rapid determination of resistance to antibiotic inhibitors of protein synthesis was developed for the gram-positive pathogens, Enterococcus faecalis and Streptococcus pneumoniae. To this purpose, a lytic response was obtained by a brief incubation with lysozyme or a mixture of lysozyme, Triton X-100, and EDTA for E. faecalis (n = 82) and S. pneumoniae (n = 51), respectively. Lysis was quantified by visualizing the released nucleoids. Antibiotic-susceptible bacteria treated with Clinical and Laboratory Standards Institute (CLSI) breakpoint doses of erythromycin, azithromycin, or doxycycline that inhibited protein synthesis demonstrated a large reduction of lysed cells with respect to the control, that is, without antibiotics. However, cell lysis prevention was much lower in nonsusceptible strains, with unsuccessful inhibition of protein synthesis. ROC analysis showed that a reduction value of ≥35.6% and ≥40.4% discriminates susceptible and nonsusceptible strains for erythromycin and for doxycycline, respectively, in E. faecalis, whereas ≥20.0% is adequate for both macrolides and doxycycline in S. pneumoniae. Resistant stains were identified in 90-120 min with sensitivity and specificity between 91.7% and 100%. This is a proof of concept that evaluation of the lytic response may be a rapid and efficient test for determination of resistance to antibiotic inhibitors of protein synthesis.

Probing minority population of antibiotic-resistant bacteria

The evolution and spread of antibiotic-resistant pathogens has become a major threat to public health. Advanced tools are urgently needed to quickly diagnose antibiotic-resistant infections to initiate appropriate treatment. Here we report the development of a highly sensitive flow cytometric method to probe minority population of antibiotic-resistant bacteria via single cell detection. Monoclonal antibody against TEM-1 β-lactamase and Alexa Fluor 488-conjugated secondary antibody were used to selectively label resistant bacteria green, and nucleic acid dye SYTO 62 was used to stain all the bacteria red. A laboratory-built high sensitivity flow cytometer (HSFCM) was applied to simultaneously detect the side scatter and dual-color fluorescence signals of single bacteria. By using E. coli JM109/pUC19 and E. coli JM109 as the model systems for antibiotic-resistant and antibiotic-susceptible bacteria, respectively, as low as 0.1% of antibiotic-resistant bacteria were accurately quantified. By monitoring the dynamic population change of a bacterial culture with the administration of antibiotics, we confirmed that under the antimicrobial pressure, the original low population of antibiotic-resistant bacteria outcompeted susceptible strains and became the dominant population after 5hours of growth. Detection of antibiotic-resistant infection in clinical urine samples was achieved without cultivation, and the bacterial load of susceptible and resistant strains can be faithfully quantified. Overall, the HSFCM-based quantitative method provides a powerful tool for the fundamental studies of antibiotic resistance and holds the potential to provide rapid and precise guidance in clinical therapies.

Pneumonia Pathogen Characterization Is an Independent Determinant of Hospital Readmission

BACKGROUNDHospital readmissions for pneumonia occur often and are difficult to predict. For fiscal year 2013, the Centers for Medicare & Medicaid Services readmission penalties have been applied to acute myocardial infarction, heart failure, and pneumonia. However, the overall impact of pneumonia pathogen characterization on hospital readmission is undefined.METHODSThis was a retrospective 6-year cohort study (August 2007 to September 2013).RESULTSWe evaluated 9,624 patients with a discharge diagnosis of pneumonia. Among these patients, 4,432 (46.1%) were classified as having culture-negative pneumonia, 1,940 (20.2%) as having pneumonia caused by antibiotic-susceptible bacteria, 2,991 (31.1%) as having pneumonia caused by potentially antibiotic-resistant bacteria, and 261 (2.7%) as having viral pneumonia. The 90-day hospital readmission rate for survivors (n = 7,637, 79.4%) was greatest for patients with pneumonia attributed to potentially antibiotic-resistant bacteria (11.4%) followed by viral pneumonia (8.3%), pneumonia attributed to antibiotic-susceptible bacteria (6.6%), and culture-negative pneumonia (5.8%) (P < .001). Multiple logistic regression analysis identified pneumonia attributed to potentially antibiotic-resistant bacteria to be independently associated with 90-day readmission (OR, 1.75; 95% CI, 1.56-1.97; P < .001). Other independent predictors of 90-day readmission were Charlson comorbidity score > 4, cirrhosis, and chronic kidney disease. Culture-negative pneumonia was independently associated with lower risk for 90-day readmission.CONCLUSIONSReadmission after hospitalization for pneumonia is relatively common and is related to pneumonia pathogen characterization. Pneumonia attributed to potentially antibiotic-resistant bacteria is associated with an increased risk for 90-day readmission, whereas culture-negative pneumonia is associated with lower risk for 90-day readmission.

Exposure to phages has little impact on the evolution of bacterial antibiotic resistance on drug concentration gradients

The use of phages for treating bacterial pathogens has recently been advocated as an alternative to antibiotic therapy. Here, we test a hypothesis that bacteria treated with phages may show more limited evolution of antibiotic resistance as the fitness costs of resistance to phages may add to those of antibiotic resistance, further reducing the growth performance of antibiotic-resistant bacteria. We did this by studying the evolution of phage-exposed and phage-free Pseudomonas fluorescens cultures on concentration gradients of single drugs, including cefotaxime, chloramphenicol, and kanamycin. During drug treatment, the level of bacterial antibiotic resistance increased through time and was not affected by the phage treatment. Exposure to phages did not cause slower growth in antibiotic-resistant bacteria, although it did so in antibiotic-susceptible bacteria. We observed significant reversion of antibiotic resistance after drug use being terminated, and the rate of reversion was not affected by the phage treatment. The results suggest that the fitness costs caused by resistance to phages are unlikely to be an important constraint on the evolution of bacterial antibiotic resistance in heterogeneous drug environments. Further studies are needed for the interaction of fitness costs of antibiotic resistance with other factors.

Secular Trends in Nosocomial Bloodstream Infections: Antibiotic-Resistant Bacteria Increase the Total Burden of Infection

It is unknown whether rising incidence rates of nosocomial bloodstream infections (BSIs) caused by antibiotic-resistant bacteria (ARB) replace antibiotic-susceptible bacteria (ASB), leaving the total BSI rate unaffected. We investigated temporal trends in annual incidence densities (events per 100 000 patient-days) of nosocomial BSIs caused by methicillin-resistant Staphylococcus aureus (MRSA), ARB other than MRSA, and ASB in 7 ARB-endemic and 7 ARB-nonendemic hospitals between 1998 and 2007. 33 130 nosocomial BSIs (14% caused by ARB) yielded 36 679 microorganisms. From 1998 to 2007, the MRSA incidence density increased from 0.2 to 0.7 (annual increase, 22%) in ARB-nonendemic hospitals, and from 3.1 to 11.7 (annual increase, 10%) in ARB-endemic hospitals (P = .2), increasing the incidence density difference between ARB-endemic and ARB-nonendemic hospitals from 2.9 to 11.0. The non-MRSA ARB incidence density increased from 2.8 to 4.1 (annual increase, 5%) in ARB-nonendemic hospitals, and from 1.5 to 17.4 (annual increase, 22%) in ARB-endemic hospitals (P < .001), changing the incidence density difference from -1.3 to 13.3. Trends in ASB incidence densities were similar in both groups (P = .7). With annual increases of 3.8% and 5.4% of all nosocomial BSIs in ARB-nonendemic and ARB-endemic hospitals, respectively (P < .001), the overall incidence density difference of 3.8 increased to 24.4. Increased nosocomial BSI rates due to ARB occur in addition to infections caused by ASB, increasing the total burden of disease. Hospitals with high ARB infection rates in 2005 had an excess burden of BSI of 20.6 per 100 000 patient-days in a 10-year period, mainly caused by infections with ARB.