Effect Of Antibiotic Exposure Research Articles

Prenatal and postnatal exposure to antibiotics and risk of food allergy in the offspring: A nationwide birth cohort study in South Korea.

There are only preliminary studies examining the associations of postnatal antibiotic exposure with food allergy in childhood, and the effect of antibiotic exposure in utero has not been resolved. Thus, we aimed to investigate the effect of prenatal and postnatal antibiotic exposure on the risk of food allergy in childhood. Using the nationwide birth cohort in South Korea, all 3,163,206 infants (pairing mother; n = 2,322,735) born in South Korea between 2010 and 2017 were included in the analysis. The primary outcome was the diagnosis of food allergy, and the observation period was between January 1, 2009, and December 31, 2020. We implemented four different designs for the study, which consisted of a full unmatched cohort, 1:1 propensity-matched cohort, sibling comparison cohort, and health screening cohort along with multiple subgroup analyses. During the follow-up period (median 6.92 years [IQR, 4.72-9.00]) of the 3,161,858 infants (52.6% male) in the birth cohort, 29,973 (1.9%) were diagnosed with food allergies. After a 1:1 propensity score matching, the use of antibiotics increased the risk of overall food allergy (prenatal [HR, 1.05; 95% CI, 1.04-1.09] and postnatal [HR, 1.05; 95% CI, 1.01-1.10] periods). The association was more significantly accentuated when antibiotic exposure was used in the short term, and the children were born preterm or with low birthweight; however, a trimester-specific effect was not observed. We observed more pronounced risks of food allergy in the health screening cohort (prenatal, 17%; postnatal, 15%), thus addressing the adverse effects of critical factors including maternal BMI, smoking status, and type of infant feeding. Similar trends were observed across all four differnt cohorts. This study reported a moderate association between early-life antibiotic use and subsequent food allergy during childhood throughout four different designs of analyses. This study suggests that clinicians need to consider the risks and benefits of antibiotics when administering antibiotics to individuals in the prenatal and postnatal periods.

Effects of antibiotic exposure on bioreactor treatment efficiency and dynamic migration of resistance genes in landfill leachate

Different concentrations of tetracycline (TC) (10 and 30 mg/L) were added to the anaerobic-anoxic-aerobic reactor to investigate the changes in effluent quality, sludge performance and the dynamic migration of antibiotic resistance genes (ARGs) in simulated landfill leachate. The maximum removal rates of COD, TN, and TP occurred at a TC concentration of 10 mg/L, reaching 75.99 %, 50.46 %, and 60.26 %, while the removal efficiency of NH3-N continued to decline. Microorganisms secreted abundant extracellular polymeric substance (EPS) and combined with antibiotic to form a stable and dense EPS antibiotic complex to resist adverse stress. The concentration of heavy metals showed a trend of first increasing and then decreasing, especially Mn and Zn. At a concentration of 10 mg/L TC, aerobic condition weakened ARGs, while anaerobic facilitated the proliferation of ARGs. The tetA and tetM in leachate were positively correlated with TC, TP, TN, NH3-N, and COD (P < 0.05), while the diffusion and transmission of ARGs in sludge were under the superimposed pressure of TC, various heavy metals, and EPS. Moreover, changes in bacterial communities drove the release of ARGs. To analyze the potential risks of ARGs in landfill leachate under antibiotic exposure, providing clues for the management and risk assessment of sewage biological treatment facilities.

Vertical migration and dissipation of oxytetracycline induces the recoverable shift in microbial community and antibiotic resistance

Antibiotic resistance gene (ARG) spread in anthropogenic polluted soils is believed to be accelerated by the incidental inputs of antibiotics via fertilizing and irrigation, and endangering food and human health. However, due to the complex nature of substrates and uncertain microbial responses, the primary drivers of ARG dissemination remain unclear. To address this concern, the effects of antibiotic inputs on soil microbes and antibiotic resistance under simulated natural conditions was investigated in this study. Specifically, four flow-through reactors with gravity flow were established, and the oxytetracycline (OTC) a typical antibiotic in agricultural soils was studied at environmental concentrations (i.e. 0.1, 1 and 10 mg/kg) for 31 days. The vertical distribution and dissipation of OTC were profiled by measuring the residuals in layers over time. Correspondingly, the effects of antibiotic exposure on microbial communities and ARG abundances were studied. The results showed that the average exposure intensity of OTC in different soil layers ranged in 0.03–6.45 mg/kg, and resulted in different dissipation kinetics. In addition, top layer was found to be the main site of OTC reduction, where OTC dissipated at magnitude of 74.0–96.6 %, depending on the initial OTC concentration. OTC migration and dissipation resulted in the shift of community composition to the extent of 0.25–0.33 in terms of Bray-Curtis distance, which partially recovered over time. And the achievement of alternative community compositions was supposed to be largely affected by the microbial interaction. Along with the community changes, a short-term accumulation of resistance genes was detected, while the relative abundance of indicator ARGs, i.e. tetG and mexB, rising up to 10-fold higher than the initial, although eventually decayed. Collective findings of this study indicated that antibiotics at environmental concentrations might trigger extra microbial interactions and thereby reducing the demand for ARGs accumulation. It provided valuable understandings in the risk of antibiotic spillage, especially for the incident exposure at the environmentally relevant concentrations.

Effect of Antibiotic Exposure on Staphylococcus epidermidis Responsible for Catheter-Related Bacteremia.

Coagulase-negative staphylococci (CoNS) and especially Staphylococcus epidermidis are responsible for health care infections, notably in the presence of foreign material (e.g., venous or central-line catheters). Catheter-related bacteremia (CRB) increases health care costs and mortality. The aim of our study was to evaluate the impact of 15 days of antibiotic exposure (ceftobiprole, daptomycin, linezolid and vancomycin) at sub-inhibitory concentration on the resistance, fitness and genome evolution of 36 clinical strains of S. epidermidis responsible for CRB. Resistance was evaluated by antibiogram, the ability to adapt metabolism by the Biofilm Ring test® and the in vivo nematode virulence model. The impact of antibiotic exposure was determined by whole-genome sequencing (WGS) and biofilm formation experiments. We observed that S. epidermidis strains presented a wide variety of virulence potential and biofilm formation. After antibiotic exposure, S. epidermidis strains adapted their fitness with an increase in biofilm formation. Antibiotic exposure also affected genes involved in resistance and was responsible for cross-resistance between vancomycin, daptomycin and ceftobiprole. Our data confirmed that antibiotic exposure modified bacterial pathogenicity and the emergence of resistant bacteria.

Effect of antibiotic exposure on the characteristics of activated sludge in a landfill leachate biological treatment system

ABSTRACT Changes in the activated sludge performance in an anaerobic/aerobic biological treatment system for leachate was discussed under the condition of tetracycline (TC) exposure. The results show that a low concentration of TC did not have an obvious effect on the removal of chemical oxygen demand (COD) while a high concentration of TC had a certain promoting effect. Under the stimulation of TC, the particle size distribution of anaerobic/aerobic sludge tended to be more uniform, the particle size of anaerobic sludge decreased while the settleability increased; however, the particle size of aerobic sludge increased due to bulking. With the addition of TC, the concentration of most heavy metal ions in sludge samples increased.TC exposure results in the release of a large amount of extracellular polymeric substances (EPS), thus leading to a smoother surface of anaerobic sludge and a rougher surface of aerobic sludge. The high removal efficiency of COD under the high concentration of TC was also presumed to be due to EPS promoting the microbial absorption of anaerobic substances in the leachate. The results clearly showed that TC had a bacteriostatic effect. After antibiotic exposure, the abundance and diversity index of bacteria in each reactor decreased obviously, the microbial community evolved, and the dominant species at the genus and phylum levels of anaerobic/aerobic reactors changed. This study provides a better understanding the effect of TC on activated sludge and has reference value for the management of antibiotic exposure in leachate treatment facilities.

Antibiotic exposure and risk of overweight/obesity in school children: A multicenter, case-control study from China

BackgroundAlthough the use of antibiotics during early life has been associated with increased risk of adipogenesis, effect of antibiotic exposure from various sources, including food or drinking water, on adiposity in children is largely unknown. ObjectiveTo investigate associations between urinary biomarkers of multiple antibiotics and risk of adipogenesis in school children. MethodsThis case-control study recruited 410 overweight/obese school children aged 6–9 years and 410 controls from Shandong and Guangdong Province, China, matched on sex, age and school. Diagnosis of overweight and obesity was based on body mass index-based criteria derived from national data. Urinary concentrations of 45 antibiotics from 8 categories (macrolides, β-lactams, tetracyclines, fluoroquinolones, sulfonamides, phenicols, lincosamides, and quinoxalines), including 6 human antibiotics (HAs), 6 antibiotics preferred as HAs (PHAs), 16 veterinary antibiotics (VAs), and 17 antibiotics preferred as VA (PVAs), were measured by ultra-performance liquid chromatography coupled to triple-quadrupole tandem mass spectrometry. Conditional logistic regression analyses were used to assess odds ratios (ORs) of childhood overweight/obesity in relation to urinary antibiotic concentrations. ResultsA total of 32 antibiotics were found in urine samples with an overall detection frequency of 92.93 %. Children with overweight/obesity have higher veterinary antibiotic levels than those with normal weight. Compared with undetected levels of antibiotics, the multivariable-adjusted ORs (95 % confidence interval) of overweight/obesity for high levels of antibiotics divided according to median values were 1.63 (1.02, 2.62) for florfenicol, 1.62 (1.04, 2.54) for phenicols, and 1.41 (0.97, 2.04) for sum of VAs and PVAs. These associations predominantly existed in boys and remained significant in florfenicol after FDR multiple testing correction (FDR adjusted p < 0.05). ConclusionExposure to certain antibiotic for veterinary use mainly from food or drinking water was associated with an increased risk of adipogenesis in children. Further studies are needed to confirm our findings and clarify the underlying mechanisms.

Effect of Antibiotic Exposure on Upper Respiratory Tract Bacterial Flora.

BackgroundThe human microbiota modulates the immune system and forms the surface flora. Antibiotic administration causes dysbiosis in the intestinal flora. It is not clear if antibiotic administration in the community effects the upper airway flora in the mid-term or long-term. This study aims to define long-term influence of antibiotics on upper airway flora.Material/MethodsIn this prospective study, aerobic microbiological analysis of nasal and nasopharyngeal surfaces was performed. Antibiotic administration history of the last 6 months was retrieved using the social insurance database. Culture results of antibiotic-treated and antibiotic-naïve subjects were compared by Pearson’s chi-square test or Fisher’s exact test.ResultsA total of 210 subjects were included in the study. Normal flora were documented in 86 nasal swabs and 99 nasopharyngeal swabs. Most of the remaining cases demonstrated gram-positive bacterial overgrowth. There were 113 subjects who did not receive any antibiotic, and 93% of the remaining 97 patients received broad-spectrum antibiotics. Statistical analysis showed that nasal and nasopharyngeal flora did not change upon antibiotic administration, but antibiotic administration during the last month caused increased methicillin resistance development of coagulase-negative Staphylococcus and Staphylococcus aureus microorganisms.ConclusionsAntibiotic exposure did not lead to perturbations in general composition of upper airway flora within 6 months, although the incidence of methicillin resistance in coagulase-positive and -negative Staphylococci demonstrated significant increases when patients received antibiotic during the last month. This should be considered in case of broad-spectrum antibiotic administration, since methicillin resistance increases the morbidity and mortality of nosocomial Staphylococcus infections.

Metatranscriptomic insight into the effects of antibiotic exposure on performance during anaerobic co-digestion of food waste and sludge

Antibiotics are inevitably entered into anaerobic co-digestion (AcoD) system of food waste (FW) and sludge along with the addition of abundant antibiotic-containing activated sludge. However, the in-depth insights into antibiotics affecting AcoD performance have not comprehensively studied. In present study, the results showed that tetracycline (TC), sulfamethoxazole (SMZ) and erythromycin (ERY) inhibited and delayed methane production except for 5 mg/L ERY. By comparison, TC and SMZ significantly inhibited the cumulative methane yields (one-way ANOVA, p < 0.01), and the inhibition effects were magnified as the antibiotic level increased. Physicochemical and methane yield analysis indicated antibiotics inhibited hydrolysis process and delayed methanogenesis process, which was in line with the declined abundance of acetogenic Proteiniphilum and hydrogenotrophic Methanobacterium during AcoD. Furthermore, metatranscriptomic analysis demonstrated the microbial activities of major organic and energy metabolism were down-regulated under antibiotics exposure, thereby down-regulating the expressions of key coenzymes (coenzymes M, F420, methanofuran) biosynthesis for methanogenesis and methane metabolism. The declined methanogenesis activity was completely consistent with the inhibited activity of dominant Methanosarcina and methane production, proving the importance of Methanosarcina on methane production. This study provides new metatranscriptomic evidence into the effects of antibiotics on methanogenesis during AcoD.

The effect of intestinal microbiota dysbiosis on growth and detection of carbapenemase-producing Enterobacterales within an in vitro gut model

Carbapenemase-producing Enterobacterales (CPE) can colonize the gut and are of major clinical concern. Identification of CPE colonization is problematic; there is no gold-standard detection method, and the effects of antibiotic exposure and microbiota dysbiosis on detection are unknown. Based on a national survey we selected four CPE screening assays in common use. We used a clinically reflective invitro model of human gut microbiota to investigate the performance of each test to detect three different CPE strains under different, clinically relevant antibiotic exposures. Twelve gut models were seeded with a pooled faecal slurry and exposed to CPE either before, after, concomitant with, or in the absence of piperacillin-tazobactam (358 mg/L, 3× daily, seven days). Total Enterobacterales and CPE populations were enumerated daily. Regular screening for CPE was performed using Cepheid Xpert® Carba-R molecular test, and with Brilliance™ CRE, Colorex™ mSuperCARBA and CHROMID® CARBA SMART agars. Detection of CPE when the microbiota are intact is problematic. Antibiotic exposure disrupts microbiota populations and allows CPE proliferation, increasing detection. The performances of assays varied, particularly with respect to different CPE strains. The Cepheid assay performed better than the three agar methods for detecting a low level of CPE within an intact microbiota, although performance of all screening methods was comparable when CPE populations increased in a disrupted microbiota. CPE strains differed in their dynamics of colonization in an invitro gut model and in their subsequent response to antibiotic exposure. This affected detection by molecular and screening methods, which has implications for the sensitivity of CPE screening in healthcare settings.

The effects of antibiotic exposure on asthma in children with atopic dermatitis

Early-life antibiotic use is associated with allergic diseases. The risk factors for the progression from atopic dermatitis (AD) to asthma or allergic rhinitis are still unknown. We aimed to investigate the association between exposure to different antibiotics and the risk of new-onset asthma in children with AD. By using the Longitudinal Health Insurance Database 2005, we selected AD patients less than 6 years old identified by ICD-9-CM code 691.8. The case group was defined as those having new-onset asthma, and the control group was defined as those without an asthma history. Information on antibiotic exposure in the 5 years prior to the index date was collected from drug prescription records. We estimated the adjusted odds ratio by using conditional logistic regression, adjusted for age, sex, index year, other potential risk factors and antibiotics. Antibiotic exposure was associated with the development of asthma in patients with AD (aOR = 3.68, 95% CI 2.13–6.36), particularly for patients less than 5 years old (aOR = 4.14, 95% CI 2.24–7.64) (p for trend < 0.001), even though lower cumulative antibiotic defined daily doses (DDDs) were associated with new-onset asthma occurrence. Antibiotic exposure, especially macrolide exposure, is associated with an increased risk of asthma in patients with AD.

Antibiotic exposure windows and the efficacy of immune checkpoint blockers in patients with cancer: a meta-analysis.

Immune checkpoint blockers (ICBs) improve the survival of patients with cancer, but primary or acquired drug resistance is inevitable. Intestinal microorganisms play an important role in immunotherapy and antitumor response, and antibiotic use can cause changes in intestinal microbial abundance and diversity. At present, the effects of antibiotic exposure on the anticancer activity of immunotherapy remain controversial. We performed a meta-analysis of relevant studies retrieved from electronic databases to assess the effects of the time window of antibiotic exposure on the efficacy of immune checkpoint inhibitors (ICIs). In accordance with the definition of antibiotic use in different articles, the time window of antibiotic exposure was divided into three groups, namely, Groups 1 (antibiotic use within 2 months before or after ICI), 2 (antibiotic use before ICI), and 3 (antibiotic use anytime during ICI). After retrieval from the PubMed and the Embase databases, 39 cohorts were included. In group 1, progression-free survival [PFS; hazard ratio (HR) =1.81, 95% confidence interval (CI): 1.40-2.34] and overall survival (OS; HR =1.81, 95% CI: 1.43-2.28) were prolonged in patients without antibiotic use. In group 2, the subgroup analysis showed that antibiotic use had no effect on PFS (HR =0.90, 95% CI: 0.65-1.26) and OS (HR =1.53, 95% CI: 0.89-2.62) when the exposure window defined as 0-3 months. In Group 3, pooled results indicated that PFS (HR =0.78, 95% CI: 0.65-0.93) was prolonged in patients with antibiotic during immunotherapy, and no difference was observed in the OS data (HR =0.98, 95% CI: 0.78-1.24) between the patients with antibiotic and without antibiotic. Antibiotic use in shortly time (within before or after 2 months) around the initiation of immunotherapy was remarkably related to the efficacy of ICIs. A different scenario could be observed that during the long-term treatment of ICIs, the effect of antibiotic exposure seems to be eliminated.

Antibiotic affects the gut microbiota composition and expression of genes related to lipid metabolism and myofiber types in skeletal muscle of piglets

BackgroundEarly-life antibiotic administration is known to affect gut microbiota and host adiposity, but the effects of antibiotic exposure on skeletal muscle properties remain unknown. The present study evaluated the changes in skeletal muscle properties including myofiber characteristics and composition, as well as intramuscular fat (IMF) content in skeletal muscle of piglets when exposed to a tylosin-containing diet.ResultsA total of 18 piglets (28 days of age) were randomly allocated into two groups: control basal diet (Control) and Control + 100 mg tylosin phosphate/kg of feed (Antibiotic). The trial lasted for 39 days. High-throughput amplicon sequencing revealed that no significant difference in initial gut microbiota composition was existed between Control and Antibiotic groups. Antibiotic administration increased body weight and growth rate and decreased feed to gain ratio of pigs (P < 0.05). The carcass lean and fat volumes of pigs were increased by the tylosin administration (P < 0.05). Antibiotic treatment increased myofiber density and the expression of genes related to type I and type IIb myofibers in longissimus muscle (P < 0.05). The IMF content in longissimus muscle was increased by antibiotic exposure (P < 0.05). Antibiotic administration increased expression of genes related to fatty acid uptake and de novo synthesis, and decreased expression of genes related to triglyceride hydrolysis (P < 0.05). Tylosin administration affected taxonomic distribution and beta diversity of the caecal and colonic microbiota of piglets.ConclusionThese results confirm that the growth performance, myofiber composition and muscle lipid metabolism are affected by antibiotic administration, which may be associated with an altered gut microbiota, suggesting that the gut microbiota could be served as a potential target for modulating skeletal muscle properties of host.

Broad-spectrum suppression of bacterial pneumonia by aminoglycoside-propagated Acinetobacter baumannii.

Antimicrobial resistance is increasing in pathogenic bacteria. Yet, the effect of antibiotic exposure on resistant bacteria has been underexplored and may affect pathogenesis. Here we describe the discovery that propagation of the human pathogen Acinetobacter baumannii in an aminoglycoside antibiotic results in alterations to the bacterium that interact with lung innate immunity resulting in enhanced bacterial clearance. Co-inoculation of mice with A. baumannii grown in the presence and absence of the aminoglycoside, kanamycin, induces enhanced clearance of a non-kanamycin-propagated strain. This finding can be replicated when kanamycin-propagated A. baumannii is killed prior to co-inoculation of mice, indicating the enhanced bacterial clearance results from interactions with innate host defenses in the lung. Infection with kanamycin-propagated A. baumannii alters the kinetics of phagocyte recruitment to the lung and reduces pro- and anti-inflammatory cytokine and chemokine production in the lung and blood. This culminates in reduced histopathologic evidence of lung injury during infection despite enhanced bacterial clearance. Further, the antibacterial response induced by killed aminoglycoside-propagated A. baumannii enhances the clearance of multiple clinically relevant Gram-negative pathogens from the lungs of infected mice. Together, these findings exemplify cooperation between antibiotics and the host immune system that affords protection against multiple antibiotic-resistant bacterial pathogens. Further, these findings highlight the potential for the development of a broad-spectrum therapeutic that exploits a similar mechanism to that described here and acts as an innate immunity modulator.

Neonatal microbiota development and the effect of early life antibiotics are determined by two distinct settler types

The neonatal period, during which the initial gut microbiota is acquired, is a critical phase. The healthy development of the infant’s microbiome can be interrupted by external perturbations, like antibiotics, which are associated with profound effects on the gut microbiome and various disorders later in life. The aim of this study was to investigate the development of intestinal microbiota and the effect of antibiotic exposure during the first three months of life in term infants. Fecal samples were collected from healthy infants and infants who received antibiotics in the first week of life at one week, one month, and three months after birth. Microbial composition was analyzed using IS-pro and compared between antibiotics-treated and untreated infants. In total, 98 infants, divided into four groups based on feeding type and delivery mode, were analyzed. At one week of age, samples clustered into two distinct groups, which were termed “settler types”, based on their Bacteroidetes abundance. Caesarean-born infants belonged to the low-Bacteroidetes settler type, but vaginally-born infants were divided between the two groups. The antibiotics effect was assessed within a subgroup of 45 infants, vaginally-born and exclusively breastfed, to minimize the effect of other confounders. Antibiotics administration resulted in lower Bacteroidetes diversity and/or a delay in Bacteroidetes colonization, which persisted for three months, and in a differential development of the microbiota. Antibiotics resulted in pronounced effects on the Bacteroidetes composition and dynamics. Finally, we hypothesize that stratification of children’s cohorts based on settler types may reveal group effects that might otherwise be masked.

Assessing the effect of high doses of ampicillin on five marine and freshwater phytoplankton species: a biodegradation perspective

Previous studies have identified several effects of antibiotic exposure at doses typically found in natural water (~μg). However, high doses of antibiotics can be found near wastewater treatment plants, and antibiotic concentrations in natural watercourses are likely to increase due to continuous current inputs. Therefore, the systematic evaluation of the susceptibility of phytoplankton species to antibiotics in water should be conducted for an improved risk assessment and the development of biotechnology for antibiotic residue management. The aim of the present study was, therefore, to investigate the response to high concentrations of ampicillin in several microalgae and cyanobacteria species with consideration of potential biodegradation applications for industrial and sanitary wastewaters. Pure laboratory cultures of freshwater (Dictyosphaerium chlorelloides, Chlamydomonas reinhardtii and Microcystis aeruginosa) and marine (Emiliania huxleyi and Prochloron sp.) species were exposed to several doses of ampicillin (6–14 mg L−1). Cell growth and other functions were followed in each species for up to a month. The results revealed that the species susceptibility to ampicillin varied greatly. No effect was observed in the chlorophytes, M. aeruginosa presented high inhibition and microcystin stimulation, upregulation/enhancement occurred in E. huxleyi, and photochemical stress occurred in the marine cyanobacterium Prochloron sp. Moreover, we observed that the ampicillin effect varied over time in susceptible species. Despite the variability of response, all the species presented high rates of antibiotic degradation. From these bioassays, it can be inferred that the effect of ampicillin cannot be generalized to microalgae groups. Additionally, the potential of microalgae to mitigate antibiotic impacts by degradation is a novel aspect yet to be investigated.

Microbiological Diagnostic Performance of Metagenomic Next-generation Sequencing When Applied to Clinical Practice.

Metagenomic next-generation sequencing (mNGS) was suggested to potentially replace traditional microbiological methodology because of its comprehensiveness. However, clinical experience with application of the test is relatively limited. From April 2017 to December 2017, 511 specimens were collected, and their retrospective diagnoses were classified into infectious disease (347 [67.9%]), noninfectious disease (119 [23.3%]), and unknown cases (45 [8.8%]). The diagnostic performance of pathogens was compared between mNGS and culture. The effect of antibiotic exposure on detection rate was also assessed. The sensitivity and specificity of mNGS for diagnosing infectious disease were 50.7% and 85.7%, respectively, and these values outperformed those of culture, especially for Mycobacterium tuberculosis (odds ratio [OR], 4 [95% confidence interval {CI}, 1.7-10.8]; P < .01), viruses (mNGS only; P < .01), anaerobes (OR, ∞ [95% CI, 1.71-∞]; P < .01) and fungi (OR, 4.0 [95% CI, 1.6-10.3]; P < .01). Importantly, for mNGS-positive cases where the conventional method was inconclusive, 43 (61%) cases led to diagnosis modification, and 41 (58%) cases were not covered by empirical antibiotics. For cases where viruses were identified, broad-spectrum antibiotics were commonly administered (14/27), and 10 of 27 of these cases were suspected to be inappropriate. Interestingly, the sensitivity of mNGS was superior to that of culture (52.5% vs 34.2%; P < .01) in cases with, but not without, antibiotic exposure. mNGS could yield a higher sensitivity for pathogen identification and is less affected by prior antibiotic exposure, thereby emerging as a promising technology for detecting infectious diseases.

Antibiotics associated with acquisition of carbapenem-resistant Pseudomonas aeruginosa in ICUs: a multicentre nested case-case-control study.

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) strains are involved in severe infections, mostly in ICUs. Exposure to antibiotics other than carbapenems may be associated with isolation of CRPA; therefore, we aimed to identify those antibiotics using the case-case-control study design. A case-case-control study was conducted in 2015 in a prospective multicentre cohort that included 1808 adults hospitalized in 2009 in 10 French ICUs. Patients were screened for P. aeruginosa at admission to the ICU and then weekly. Cases were patients with CRPA and patients with carbapenem-susceptible P. aeruginosa (CSPA) isolation. Controls were patients without P. aeruginosa isolation, matched with each case according to centre, length of stay and hospitalization period. Effects of antibiotic exposure were explored, after adjusting for prior treatment with carbapenems and confounding factors comprising colonization pressure with two logistic regression models. The two models were compared to identify specific risk factors for CRPA isolation. Fifty-nine CRPA, 83 CSPA and 142 controls were compared. In adjusted multivariable analyses, exposure to carbapenems and to antibiotics belonging to the group of β-lactams inactive against P. aeruginosa were independent risk factors for CRPA isolation (OR, 1.205; 95% CI, 1.079-1.346 and OR, 1.101; 95% CI, 1.010-1.201, respectively). Conversely, exposure to β-lactams active against P. aeruginosa was an independent protective factor for CSPA isolation (OR, 0.868; 95% CI, 0.772-0.976). Besides carbapenem exposure, exposure to β-lactams inactive against P. aeruginosa was a specific risk factor for CRPA isolation. Clinicians should counterweigh the potential benefits of administering these antibiotics against the increased risk of CRPA infection.

Chlortetracycline and florfenicol induce expression of genes associated with pathogenicity in multidrug-resistant Salmonella enterica serovar Typhimurium

BackgroundMultidrug-resistant (MDR) Salmonella enterica serovar Typhimurium (S. Typhimurium) is a serious public health threat as infections caused by these strains are more difficult and expensive to treat. Livestock serve as a reservoir for MDR Salmonella, and the antibiotics chlortetracycline and florfenicol are frequently administrated to food-producing animals to treat and prevent various diseases. Therefore, we evaluated the response of MDR S. Typhimurium after exposure to these two antibiotics.ResultsWe exposed four MDR S. Typhimurium isolates to sub-inhibitory concentrations of chlortetracycline (16 and 32 µg/ml) or florfenicol (16 µg/ml) for 30 min during early-log phase. Differentially expressed genes following antibiotic treatment were identified using RNA-seq, and genes associated with attachment and those located within the Salmonella pathogenicity islands were significantly up-regulated following exposure to either antibiotic. The effect of antibiotic exposure on cellular invasion and motility was also assessed. Swimming and swarming motility were decreased due to antibiotic exposure. However, we observed chlortetracycline enhanced cellular invasion in two strains and florfenicol enhanced invasion in a third isolate.ConclusionsChlortetracycline and florfenicol exposure during early-log growth altered the expression of nearly half of the genes in the S. Typhimurium genome, including a large number of genes associated with virulence and pathogenesis; this transcriptional alteration was not due to the SOS response. The results suggest that exposure to either of these two antibiotics may lead to the expression of virulence genes that are typically only transcribed in vivo, as well as only during late-log or stationary phase in vitro.

Acquisition and clearance of multidrug resistant Acinetobacter baumannii on healthy young adults concurrently burned in a dust explosion in Taiwan: the implication for antimicrobial stewardship

BackgroundInformation is limited about the effect of restricted carbapenem use on clearance of multi-drug resistant Acinetobacter baumannii (MDRAB). We sought to determine the time effect of antibiotic exposure on multi-drug resistant Acinetobacter baumannii (MDRAB) acquisition and clearance.MethodsWe conducted a retrospective observational study at the intensive care units of a tertiary medical center. Forty-two of a cohort of previously healthy young adults who were concurrently burned by a dust explosion was included. Cases consisted of those from whom MDRAB was isolated during hospitalization. Controls consisted of patients from whom MDRAB was not isolated in the same period. Use of antimicrobial agents was compared based on days of therapy per 1,000 patient-days (DOT/1,000PD). A 2-state Markov multi-state model was used to estimate the risk of acquisition and clearance of MDRAB.ResultsMDRAB was discovered in 9/42 (21.4%) individuals. The cases had significantly higher use of carbapenem (652 DOT/1,000PD vs. 385 DOT/1,000PD, P < 0.001) before MDRAB isolation. For the cases, clearance of MDRAB was associated with lower use of carbapenem (469 DOT/1,000PD vs. 708 DOT/1,000PD, P = 0.003) and higher use of non-carbapenem beta-lactam (612 DOT/1,000PD vs. 246 DOT/1,000PD, P <0.001). In multi-state model, each additional DOT of carbapenem increased the hazard of acquiring MDRAB (hazard ratio (HR), 1.08; 95% confidence interval (CI) 1.01–1.16) and each additional DOT of non-carbapenem beta-lactam increased the protection of clearing MDRAB (HR, 1.25; 95% CI 1.07–1.46).ConclusionsBoth acquisition and clearance of MDRAB were related to antibiotic exposure in a homogeneous population. Our findings suggest that early discontinuation of carbapenem could be an effective measure in antibiotic stewardship for the control of MDRAB spreading.

The Effect of Antibiotic Exposure and Specimen Volume on the Detection of Bacterial Pathogens in Children With Pneumonia.

Background.Antibiotic exposure and specimen volume are known to affect pathogen detection by culture. Here we assess their effects on bacterial pathogen detection by both culture and polymerase chain reaction (PCR) in children.Methods.PERCH (Pneumonia Etiology Research for Child Health) is a case-control study of pneumonia in children aged 1–59 months investigating pathogens in blood, nasopharyngeal/oropharyngeal (NP/OP) swabs, and induced sputum by culture and PCR. Antibiotic exposure was ascertained by serum bioassay, and for cases, by a record of antibiotic treatment prior to specimen collection. Inoculated blood culture bottles were weighed to estimate volume.Results.Antibiotic exposure ranged by specimen type from 43.5% to 81.7% in 4223 cases and was detected in 2.3% of 4863 controls. Antibiotics were associated with a 45% reduction in blood culture yield and approximately 20% reduction in yield from induced sputum culture. Reduction in yield of Streptococcus pneumoniae from NP culture was approximately 30% in cases and approximately 32% in controls. Several bacteria had significant but marginal reductions (by 5%–7%) in detection by PCR in NP/OP swabs from both cases and controls, with the exception of S. pneumoniae in exposed controls, which was detected 25% less frequently compared to nonexposed controls. Bacterial detection in induced sputum by PCR decreased 7% for exposed compared to nonexposed cases. For every additional 1 mL of blood culture specimen collected, microbial yield increased 0.51% (95% confidence interval, 0.47%–0.54%), from 2% when volume was ≤1 mL to approximately 6% for ≥3 mL.Conclusions.Antibiotic exposure and blood culture volume affect detection of bacterial pathogens in children with pneumonia and should be accounted for in studies of etiology and in clinical management.