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Jatan B. Sherchan, Tatsuya Tada, Shovita Shrestha, Hiroki Uchida, Tomomi Hishinuma, Shinichiro Morioka, Rajesh K. Shahi, Sarita Bhandari, Roshna T. Twi, Teruo Kirikae, Jeevan B. Sherchand
James Samwel Ngocho, Pius Gerald Horumpende, Marien Isaäk de Jonge, Blandina Theophil Mmbaga
Healthcare-Associated Infections (HAIs) represent one of the leading issues to patient safety as well as a significant economic burden. Similarly, Antimicrobial Use (AMU) and Resistance (AMR) represent a growing threat to global public health and the sustainability of healthcare services.
A Point Prevalence Survey (PPS) following the 2016 ECDC protocol for HAI prevalence and AMU was conducted at Ferrara University Hospital (FUH). Data were collected by a team of trained independent surveyors in 2016 and 2018. Risk factors independently associated with HAI were assessed by a multivariate logistic regression model.
Of the 1102 patients surveyed, 115 (10.4%) had an active HAI and 487 (44.2%) were on at least 1 systemic antimicrobial agent. Factors independently associated with increased HAI risk were a “Rapidly Fatal” McCabe score (expected fatal outcome within 1 year), presence of medical devices (PVC, CVC, indwelling urinary catheter or mechanically assisted ventilation) and a length of hospital stay of at least 1 week. The most frequent types of HAI were pneumonia, bloodstream infections, and urinary tract infections. Antimicrobial resistance to third-generation cephalosporins was observed in about 60% of Enterobacteriaceae.
The survey reports a high prevalence of HAI and AMU in FUH. Repeated PPSs are useful to control HAIs and AMU in large acute-care hospitals, highlighting the main problematic factors and allowing planning for improvement actions.
Community acquired pneumonia (CAP) remains a significant cause of morbidity and in-hospital mortality, and readmission rates are rising for older persons (> 65 years). Optimized treatment and nursing care will benefit patients and the health economy. Hence, there is a need to describe gaps between current clinical practice and recommendations in evidence-based guidelines for diagnostic procedures, medical treatment and nursing interventions for older patients with CAP.
Structured observations, individual ad hoc interviews and audits of patient records were carried out in an emergency department and three medical units. Data were analysed by manifest content analysis and descriptive statistics.
Thirty patients (median age 74 years) admitted with CAP and 86 physicians, nurses, physiotherapists were included. The median length of stay (LOS) was 6.5 days, in-hospital mortality was10 and 40.7% were readmitted within one month. The severity assessment tool (CURB-65) was used in 16.7% of the patients, correct antibiotic treatment prescribed for 13.3% and chest radiography (≤6 weeks post-discharge) prescribed for 22.2%. Fluid therapy, nutrition support and mobilisation plans were found to be developed sporadically, and interventions to be performed unsystematically and sparingly. Positive Expiratory Pressure therapy and oral care were the nursing interventions with lowest adherence, ranging from 18.2 to 55.6%.
Adherence to recommendations was low for several central treatment and nursing care interventions for patients with CAP with possible consequences for patients and the use of resources. Thus, there is an urgent need to identify and remove barriers to adherence to recommendations in the neglected areas in view of the potential to improve patient outcomes.
Akihiro Ito, Isao Ito, Daiki Inoue, Satoshi Marumo, Tetsuya Ueda, Hiroaki Nakagawa, Masato Taki, Atsushi Nakagawa, Shuji Tatsumi, Takashi Nishimura, Tetsuhiro Shiota, Tadashi Ishida
Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality worldwide (Arnold et al., 2013). To improve the prognosis of CAP patients, assessment of its severity is important for selecting appropriate antimicrobial agents and site of treatment, whether as an outpatient or in hospital, including a general ward or intensive care unit (ICU). Either CURB-65 (Lim et al., 2003) or the Pneumonia Severity Index (PSI) (Fine et al., 1997) is often used to assess the severity of pneumonia because they have been validated to correlate well with prognosis.
Lopamudra Ray Saraswati,
Tropical Medicine &International Health, EarlyView.
Coppi, M., Di Pilato, V., Monaco, F., Giani, T., Conaldi, P. G., Rossolini, G. M.
This work reports on the characterization of two ceftazidime-avibactam (CZA)-resistant KPC-producing Klebsiella pneumoniae (KP-14159 and KP-8788) sequentially isolated from infections occurred in a patient never treated with CZA, respectively. WGS characterization using a combined short and long reads sequencing approach revealed that both isolates belonged to the same ST258 strain, had altered outer membrane porins (a truncated OmpK35 and an Asp137Thr138 duplication in the L3 loop of OmpK36), and carried novel pKpQIL plasmid derivatives (pIT-14159 and pIT-8788, respectively) harboring two copies of the Tn4401a KPC-3-encoding transposon. Plasmid pIT-8788 was a cointegrate of pIT-14159 with a ColE replicon (that was also present in KP-14159) apparently evolved in vivo during infection. pIT-8788 was maintained at higher copy number compared with pIT-14159, and upon transfer to E. coli DH10B was able to increase CZA MIC by 32-fold. Present findings provided novel insights about mechanisms of acquired resistance to CZA, underscoring the role that evolution of broadly disseminated pKpQIL plasmid derivatives may have in increasing the blaKPC gene copy number and KPC-3 expression in the bacterial hosts. Although not self-transferable, similar elements, with multiple copies of Tn4401 and maintained at high copy number, could mediate transferable CZA resistance upon mobilization.
Qianda Zou, Shufa Zheng, Xiaochen Wang, Sijia Liu, Jiaqi Bao, Fei Yu, Wei Wu, Xianjun Wang, Bo Shen, Tieli Zhou, Zhigang Zhao, Yiping Wang, Ruchang Chen, Wei Wang, Jianbo Ma, Yongcheng Li, Xiaoyan Wu, Weifeng Shen, Fuyi Xie, Dhanasekaran Vijaykrishna, Yu Chen
Fig. 1 Fig. 2
Hatch, N. D., Ouellette, S. P.
Chlamydia trachomatis is the leading cause of bacterial sexually transmitted infections, and C. pneumoniae causes community-acquired respiratory infections. In vivo, the host immune system will release interferon-gamma (IFN) to combat infection. IFN activates human cells to produce the tryptophan (trp) catabolizing enzyme, IDO. Consequently, there is a reduction in cytosolic trp in IFN-activated host cells. In evolving to obligate intracellular dependence, Chlamydia has significantly reduced its genome size and content as it relies on the host cell for various nutrients. Importantly, C. trachomatis and C. pneumoniae are trp auxotrophs and are starved for this essential nutrient when the human host cell is exposed to IFN. To survive this, chlamydiae enter an alternative developmental state referred to as persistence. Chlamydial persistence is characterized by a halt in the division cycle, aberrant morphology, and, in the case of IFN-induced persistence, trp codon-dependent changes in transcription. We hypothesize that these changes in transcription are dependent on the particular amino acid starvation state. To investigate the chlamydial response mechanisms acting when other amino acids become limiting, we tested the efficacy of prokaryotic specific tRNA synthetase inhibitors, indolmycin and AN3365, to mimic starvation of trp and leucine, respectively. We show that these drugs block chlamydial growth and induce changes in morphology and transcription consistent with persistence. Importantly, growth inhibition was reversed when the compounds were removed from the medium. With these data, we find that indolmycin and AN3365 are valid tools that can be used to mimic the persistent state independently of IFN.
Amin-Chowdhury Z, Collins S, Sheppard C, et al.
AbstractBackgroundThe UK is experiencing a rapid increase in invasive pneumococcal disease (IPD) caused by serotypes 8, 12F and 9N; their clinical characteristics and outcomes have not been described.MethodsPublic Health England conducts enhanced national surveillance of IPD. Since 2014, general practitioners were requested to complete a surveillance questionnaire for all confirmed cases. IPD cases due to emerging serotypes were compared with those included in the 13-valent pneumococcal conjugate vaccine (PCV13) and the remaining non-PCV13 serotypes.ResultsThere were 21,592 IPD cases over four epidemiological years (2014/15-2017/18), including 20,108 (93.1%) with serotyped isolates and 17,450 (86.8%) with completed questionnaires. PCV13 serotypes were responsible for 20.1% (n=4,033) cases, while serotype 8 (3,881/20,108, 19.3%), 12F (2,365/20,108, 11.8%), and 9N (1,296/20,108, 6.5%) were together responsible for 37.5% of IPD cases. Invasive pneumonia was the most common presentation (11,424/16,346; 69.9%) and, overall, 64.1% (n=11,033) had an underlying comorbidity. The median age at IPD due to serotypes 8 (59 years; IQR, 45-72) and 12F (56 years; 41-70) was lower than serotype 9N (67 years; 53-80), PCV13 serotypes (68 years; 52-81) and the remaining non-PCV13 serotypes (70 years; 53-82). Serotype 9N IPD cases also had higher comorbidity prevalence (748/1,087, 68.8%) compared to serotype 8 (1,901/3,228, 58.9%) or 12F (1,042/1,994, 52.3%), and higher case fatality rate (212/1,128, 18.8%) compared to 8.7% (291/3,365) or 10.0% (209/2,086), respectively.ConclusionsSerotypes 8 and 12F were more likely to cause IPD in younger, healthier individuals and less likely to be fatal, while serotype 9N affected older adults with comorbidities and had a higher case fatality rate.
Charles W. Stratton,
Journal of Medical Virology, Volume 0, Issue ja, -Not available-.
With the increase of awareness of mycoplasma pneumoniae pneumonia (MPP), we found thrombosis in severe MPP (SMPP) was not rare. The aim of the study was to investigate the clinical characteristics, treatment, and long-term prognosis of MPP-associated thrombosis.
We retrospectively reviewed the medical records of 43 children with MPP-associated thrombosis between January 2013 and June 2019 at Beijing Children’s Hospital. The results of blood coagulation studies, autoimmune antibody, thrombophilia screening, contrast-enhanced lung computed tomography, echocardiography, and blood vessel ultrasonography were analyzed, as were treatment outcomes.
Forty-two patients were diagnosed with SMPP. D-dimer was higher than 5.0 mg/L in 58.1% (25/43) of patients. The mean D-dimer level was 11.1 ± 12.4 mg/L. Anticardiolipin-IgM was positive in 60.0% of patients, β2-glycoprotein-IgM in 64.0%, and lupus anticoagulant in 42.1%. Chest imaging revealed pulmonary consolidation with lobe distribution in all patients (2/3–1 lobe in 10 patients, > 1 lobe in 29 patients). In our experience, thrombosis can occur in a vessel of any part of the body, and it can be initially detected as late as 31 days after disease onset. Thrombosis in the brain and abdomen can occur early, at 5 days after disease onset. Pulmonary vessels were the most commonly involved sites in the current study, and accordingly chest pain was the most common symptom (32.6%), followed by neurological symptoms (14.0%) and abdominal pain (9.3%). Thirty-five percent of patients were asymptomatic with regard to thrombosis. All patients underwent anticoagulant therapy, and thrombus absorption took > 3 months in most patients. All patients were followed until October 2019, at which time 41 were asymptomatic and 2 had mild recurrent cough.
SMPP with pulmonary consolidation (> 2/3 lobe) was the most strongly associated risk factor for thrombosis. Thrombosis-associated symptoms may be subtle, even absent. Elevated D-dimer, specifically > 11.1 mg/L (even > 5.0 mg/L), would assist in the early diagnosis of thrombosis. The long-term prognosis of thrombosis was good after timely administration of anticoagulant therapy.
Acinetobacter baumannii is a gram-negative aerobic bacillus that is commonly causes of hospital-acquired infections. Community-acquired pneumonia caused by Acinetobacter baumannii (CAP-Ab) is rare but fatal if diagnosis and treatment are delayed. Conventional culture of clinical specimens is the main method for clinical diagnosis of A. baumannii infections which may suffer from limited positive rate and is time consuming. Timely and precise diagnosis of CAP-Ab remains challenging.
A 66-year-old man with 24 h history of acute fever and dyspnea was admitted to our hospital. He was diagnosed as severe community acquired pneumonia (CAP), septic shock, respiratory failure and acute kidney injury. Next-generation sequencing (NGS) was performed on the patient’s sputum and blood, which identified numerous A. baumannii nucleotide sequences in the sample of sputum and led to the rapid diagnosis and treatment of community acquired pneumonia caused by A. baumannii. This result was confirmed by subsequent sputum culture.
This case described that the successful application of the next generation sequencing assisting the speedy diagnosis of A. baumannii infection provides a new idea for the timely diagnosis of CAP-Ab and highlights that NGS is a promising tool in rapid etiological diagnosis of acute and severe infectious diseases.
David S. Hui, Esam EI Azhar, Tariq A. Madani, Francine Ntoumi, Richard Kock, Osman Dar, Giuseppe Ippolito, Timothy D. Mchugh, Ziad A. Memish, Christian Drosten, Alimuddin Zumla, Eskild Petersen
The city of Wuhan in China is the focus of global attention due to an outbreak of a febrile respiratory illness due to a novel coronavirus. In December 2019, there was an outbreak of pneumonia of unknown cause in Wuhan, Hubei province in China, with an epidemiological link to the Huanan Seafood Wholesale Market where there was also sale of live animals. Notification of the WHO on 31 Dec 2019 by the Chinese Health Authorities has prompted health authorities in Hong Kong, Macau, and Taiwan to step up border surveillance, and generated concern and fears that it could mark the emergence of a novel and serious threat to public health (WHO, 2020a; Parr, 2020).
Rotondo, C. M., Sychantha, D., Koteva, K., Wright, G. D.
The rise of Gram-negative pathogens expressing metallo-β-lactamases (MBLs) is a growing concern, threatening the efficacy of β-lactam antibiotics, in particular, the carbapenems. There are no inhibitors of MBLs in current clinical use. Aspergillomarasmine A (AMA) is an MBL inhibitor isolated from Aspergillus versicolor with both in vitro and in vivo ability to rescue meropenem activity in MBL-producing bacteria. Here we systematically explored the pairing of AMA with six β-lactam antibiotic partners against nineteen MBLs from each subclass (B1, B2, B3). Cell-based assays with Escherichia coli and Klebsiella pneumoniae showed that bacteria producing NDM-1 and VIM-2 of subclass B1 were the most susceptible to AMA inhibition, whereas bacteria producing CphA2 and AIM-1 of subclasses B2 and B3, respectively, were the least sensitive. Intracellular antibiotic accumulation assays and in vitro enzyme assays demonstrated that the efficacy of AMA/β-lactam combinations did not correlate with outer membrane permeability or drug efflux. We determined that the optimal β-lactam partners for AMA are the carbapenem antibiotics, and the efficacy of AMA is linked to the Zn2+ affinity of specific MBLs.
Monica Basso, Daniela Zago, Irene Pozzetto, Ettore De Canale, Renzo Scaggiante, Maria Angela Biasolo, Marta Peracchi, Francesco Onelia, Elisa Baldasso, Giorgio Palù, Saverio Giuseppe Parisi
Gao, Chang; Wang, Yeming; Gu, Xiaoying; Shen, Xinghua; Zhou, Daming; Zhou, Shujun; Huang, Jian-an; Cao, Bin; Guo, Qiang; for the Community-Acquired Pneumonia–China Network
To evaluate the prevalence of cardiac injury and its association with mortality in hospitalized patients infected with avian influenza A (H7N9) virus.
Retrospective cohort study.
A total of 133 hospitals in 17 provinces, autonomous regions, and municipalities of mainland China that admitted influenza A (H7N9) virus–infected patients between January 22, 2015, and June 16, 2017.
A total of 321 patients with influenza A (H7N9) virus infection were included in the final analysis.
Measurements and Main Results:
Demographics and clinical characteristics were collected from medical records. Cardiac injury was defined according to cardiac biomarkers, electrocardiography, or echocardiography. Among the 321 patients, 203 (63.2%) showed evidence of cardiac injury. Compared with the uninjured group, the cardiac injury group had lower PaO2/FIO2 (median, 102.0 vs 148.4 mm Hg; p < 0.001), higher Acute Physiology and Chronic Health Evaluation II score (median, 17.0 vs 11.0; p < 0.001), longer stay in the ICU (10.0 vs 9.0 d; p = 0.029), and higher proportion of in-hospital death (64.0% vs 20.3%; p < 0.001). The proportion of virus clearance until discharge or death was lower in the cardiac injury group than in the uninjured group (58.6% vs 86.4%; p < 0.001). Multivariable-adjusted Cox proportional hazards regression analysis showed that cardiac injury was associated with higher mortality (hazards ratio, 2.06; 95% CI, 1.31–3.24) during hospitalization.
Cardiac injury is a frequent condition among hospitalized patients infected with influenza A (H7N9) virus, and it is associated with higher risk of mortality.
Drs. Gao, Wang, and Gu contributed equally to this work.
Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http:/journals.lww.com/ccmjournal).
Supported, in part, by grants from National Science and Technology Major Project (2017ZX10204401004 and 2017ZX10103004); Emergency Special Project of the Ministry of Science and Technology (10600100000015001206); National Key Research and Development Program of China (2018YFC1200102); CAMS Innovation Fund for Medical Sciences (CIFMS 2018-I2M-1-003); National Science Grant for Distinguished Young Scholars (81425001/H0104); Jiangsu Province’s Key Provincial Talents Program (ZDRCA2016046); and Key Health Talents in Gusu (GSWS2019009).
The authors have disclosed that they do not have any potential conflicts of interest.
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Copyright © by 2020 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Streptococcus pneumoniae carriage is often asymptomatic but can cause invasive pneumococcal disease. Pneumococcal carriage is a prerequisite for disease, with children as main reservoir and transmitters. Childhood carriage can therefore be used to determine which serotypes circulate in the population and which may cause disease in the non-vaccinated population. In 2006, a pneumococcal conjugate vaccine (PCV7) was introduced into the Norwegian Childhood Immunisation Programme, which was replaced by the more valent PCV13 in 2011. We investigated changes in pneumococcal carriage prevalence 4 years after switching to PCV13 compared to three previous surveys, and analysed factors associated with carriage in children.
We conducted a cross-sectional study in Norway, autumn 2015, among children attending day-care centres. We collected questionnaire data and nasopharyngeal swabs to identify pneumococcal serotypes. We compared the carriage prevalence in 2015 with surveys conducted in the same setting performed before widespread vaccination (2006; n = 610), 2 years after PCV7 introduction (2008; n = 600), and 2 years after switching to PCV13 (2013; n = 874). Using multilevel logistic regression we determined the association between pneumococcal carriage and previously associated factors.
In 2015, 896 children participated, with age ranging from 8 to 80 months. The overall carriage prevalence was 48/100 children [95%CI 44–53] in 2015, 38% [29–46] lower than in 2006 pre-PCV7, and 23% [12–32] lower than in 2013, 2 years after switching to PCV13. The PCV13 carriage prevalence was 2.8/100 children [1.9–4.2] in 2015. Increasing age (p
Daniel Helldén, Kevin Baker, Tedila Habte, Esey Batisso, Nicola Orsini, Karin Källander and Tobias Alfvén
Pneumonia is one of the leading causes of death in children under 5 years worldwide. In resource-limited settings, WHO recommendations state that pneumonia can be presumptively diagnosed through the presence of cough and/or difficult breathing and a respiratory rate (RR) that is higher than age-specific cutoffs. As a new diagnostic aid the children’s automated respiration monitor (ChARM) can automatically measure and classify RR in children under 5 years, but the effect of its chest attachment on the RR has not been studied. The aim of this study was to understand if misclassification of the true RR occurred by ChARM attachment. Two hundred eighty-seven children at a health center in South Ethiopia were screened for eligibility, with 188 children aged 2–59 months enrolled in the study. The RR was measured manually before and 1, 3, and 5 minutes after ChARM attachment. The proportion of children with fast or normal RR classification at baseline and the change between RR classifications over time were analyzed. Eight (4.9%; 95% CI 2.1, 9.4) of 163 children changed RR classification from normal to fast between the baseline RR count and the 1 minute RR count. Results from this study suggest that ChARM has a minor influence on the RR of children immediately after attachment, in most cases without clinical importance.
Young-Hwan Ahn, Hyungcheol Park and Sun-Seog Kweon
In addition to the complications of leprosy, people affected by leprosy (PALs) can suffer from chronic diseases. We evaluated the recent pattern of deaths among Korean PALs and compared it with that in the general population. We analyzed the death certificate data of 1,359 PALs from 2010 through 2013. The all-cause and cause-specific standardized mortality ratio (SMR) and standardized mortality with 95% CI were calculated. Malignancy had the highest standardized mortality, with 130.9 deaths per 100,000 persons, followed by cardiovascular diseases (CVDs; 85.5 deaths) and respiratory diseases (38.2 deaths). Of malignancies, liver cancer caused the greatest number of cancer deaths (40.0 deaths). The all-cause mortality of PALs was significantly lower than that in the general population, corresponding to an SMR of 0.84 (95% CI 0.79–0.88). Deaths from malignancy and CVDs were significantly lower, corresponding to SMRs (95% CIs) of 0.88 (0.79–0.98) and 0.75 (0.67–0.84), respectively. The death rates for lung and stomach cancers were lower, whereas mortality due to liver cancer was higher, with an SMR of 1.79 (95% CI 1.43–2.22). Except for liver cancer and infection, the causes of mortality of PALs tend to be lower than that in the general population. The most common underlying cause of death in PALs was stroke, followed by ischemic heart disease, liver cancer, and pneumonia.
Célia Scherelle Boumbanda Koyo, Sandrine Lydie Oyegue-Liabagui, Oleg Mediannikov, Sébastien Cortaredona, Lady Charlene Kouna, Didier Raoult, Jean Bernard Lekana-Douki and Florence Fenollar
The epidemiology of febrile illness etiologies is under-explored in resource-poor settings. Establishing a local repertory of microorganisms circulating in blood of febrile and afebrile people is important for physicians. Blood was collected from 428 febrile and 88 afebrile children in Makokou (Gabon) and analyzed using polymerase chain reaction. Plasmodium spp. were the pathogens, which were most detected in febrile children (69.6%; 298/428) and in afebrile children (31.8%; 28/88) (P < 0.0001). Plasmodium falciparum was the most prevalent species in both febrile and afebrile children (66.8% and 27.3%, respectively). No differences were observed between febrile and afebrile children for Plasmodium malariae and Plasmodium ovale (8.2% versus 10.2% and 3.3% versus 3.4%, respectively). Triple infection with P. falciparum, P. malariae, and P. ovale was also detected in 1% of febrile children (4/428). Filariasis due to Mansonella perstans was detected in 10 febrile patients (2.3%), whereas Loa loa was detected in both febrile and afebrile children (1.4% and 2.3%, respectively). Bacterial DNA was detected in only 4.4% (19/428) of febrile children, including 13 (68.4%) who were coinfected with at least one Plasmodium species. These were Haemophilus influenzae (1.6%, 7/428), Streptococcus pneumoniae and Staphylococcus aureus (1.2%, 5/428), and Rickettsia felis (0.9%, 4/428). Coxiella burnetii, Bartonella spp., Borrelia spp., Tropheryma whipplei, Anaplasma spp., Leptospira spp., Streptococcus pyogenes, and Salmonella spp. were not detected. This study also highlights the over-prescription and the overuse of antibiotics and antimalarials. Overall, malaria remains a major health problem in Makokou. Malaria control measures must be reconsidered in this region.
K. Zhou et al.
Vena A, Giacobbe D, Mussini C, et al.
O'Donnell, K. L., Knopick, P. L., Larsen, R., Sarkar, S., Nilles, M. L., Bradley, D. S.
Yersinia pestis is the causative agent of bubonic, pneumonic, and septicemic plague. We demonstrate that TLR2-/- mice are resistant to septicemic infection by the KIM5 strain of Y. pestis KIM5 but not infection by the CO92 (pgm) strain. This resistance is dependent on TLR2, route of infection, and the isoform of YopJ. Elevated bacterial burden was found in the spleens of CO92 pgm infected animals by 24 h post infection and in the livers by 4 d. The YopJ isoform present directly contributed to cytotoxicity and inflammatory cytokine production of bone marrow derived macrophages from TLR2-/- mice. Immune cell trafficking is altered in CO92 pgm infections with an increased neutrophil infiltration to the spleen 5 d post infection. Immune cell infiltration to the liver was greater and earlier in the livers of KIM5 infected TLR2-/- mice. The functionality of the immune cells was assessed by the ability to develop reactive oxygen and nitrogen species. Our data suggests an inhibition of granulocytes to form these species in CO92 pgm infected TLR2-/- mice. These findings suggest that resistance to KIM5 in TLR2-/- mice is dependent on early immune cell trafficking and functionality.
Keith, J., Dong, Q., Sorbara, M. T., Becattini, S., Sia, J. K., Gjonbalaj, M., Seok, R., Leiner, I., Littmann, E., Pamer, E. G.
Antibiotic treatment of patients undergoing complex medical treatments can deplete commensal bacterial strains from the intestinal microbiota, thereby reducing colonization resistance against a wide range of antibiotic-resistant pathogens. Loss of colonization resistance can lead to marked expansion of Vancomycin-resistant Enterococcus faecium (VRE), Klebsiella pneumoniae (Kp) and Escherichia coli (Ec) in the intestinal lumen, predisposing patients to bloodstream invasion and sepsis. The impact of intestinal domination by these antibiotic-resistant pathogens on mucosal immune defenses and epithelial and mucin-mediated barrier integrity is unclear. We used a mouse model to study the impact of intestinal domination by antibiotic-resistant bacterial species and strains on the colonic mucosa. Intestinal colonization of Kp, Pm and E. cloacae promoted greater recruitment of neutrophils to the colonic mucosa. To test the hypothesis that the residual microbiota influence the severity of colitis caused by infection with Clostridioides difficile, we co-infected mice that were colonized with ampicillin-resistant bacteria with a virulent strain of C. difficile and monitored colonization and pathogenesis. Despite the compositional differences in the gut microbiota, the severity of C. difficile infection and mortality did not vary significantly between mice colonized with different ampicillin-resistant bacterial species. Our results suggest that the virulence mechanisms enabling C. difficile infection (CDI) and epithelial destruction outweigh the relatively minor impact of less virulent, antibiotic-resistant intestinal bacteria on the outcome of CDI.
Carvalhaes, C. G., Shortridge, D., Sader, H. S., Castanheira, M.
Meropenem-vaborbactam is approved to treat hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP), in Europe. Meropenem-vaborbactam activity was evaluated against 3,193 Pseudomonas aeruginosa and 4,790 Enterobacterales causing pneumonia in hospitalized patients (PHP), including VAP, in U.S. Susceptibility testing was performed by broth microdilution method and all carbapenem-resistant isolates were submitted to whole genome sequencing. Meropenem-vaborbactam exhibited almost complete activity against Enterobacterales (>99.9% susceptible), including CRE, and was also very active against P. aeruginosa isolates (89.5% susceptible).
A well described case of the emergence of drug resistance in Streptococcus pneumoniae meningitis during therapy with ceftriaxone monotherapy with a low bactericidal concentration in the cerebrospinal fluid. Adherence to international guidelines could possibly prevented the emergence of this resistant isolate and the adverse outcome.
Idowu, T., Zhanel, G. G., Schweizer, F.
Ceftolozane/Tazobactam is a potent β-lactam/β-lactamase inhibitor combination approved for the treatment of complicated intra-abdominal and complicated urinary tract infections and, more recently, the treatment of hospital-acquired and ventilator-associated bacterial pneumonia. Although the activities of ceftolozane are not enhanced by tazobactam against Pseudomonas aeruginosa, it remains the most potent antipseudomonal agent approved to date. Emerging data worldwide has however reported case reports of microbiological failure in patients with serious bacterial infections caused by multi-drug resistant (MDR) P. aeruginosa as a result of ceftolozane resistance development on therapy. The objective of this study is therefore to compare the efficacy of a tobramycin homodimer + ceftolozane versus ceftolozane/tazobactam alone against MDR and extensively-drug resistant (XDR) P. aeruginosa. Tobramycin homodimer, a synthetic dimer of two monomeric units of tobramycin, was developed to abrogate the ribosomal properties of tobramycin with a view to mitigating aminoglycoside-related toxicity and resistance. Herein, we report that tobramycin homodimer, a non-ribosomal aminoglycoside derivative, potentiates the activities of ceftolozane versus MDR/XDR P. aeruginosa in vitro and delays the emergence of resistance to ceftolozane/tazobactam in wild-type PAO1. This combination is also more potent than a standard ceftazidime/avibactam combination against these isolates. Conversely, a tobramycin monomer with intrinsic ribosomal properties does not potentiate ceftolozane under similar conditions. Susceptibility and checkerboard studies were assessed using serial 2-fold dilution assays, following CLSI guidelines. This strategy provides an avenue to further preserve the clinical utility of ceftolozane and enhances its spectrum of activity against one of the most difficult-to-treat pathogens in hospitals.
Abbott, I. J., van Gorp, E., Wijma, R. A., Meletiadis, J., Roberts, J. A., Mouton, J. W., Peleg, A. Y.
Oral fosfomycin trometamol is licensed as a single oral dose for the treatment of uncomplicated urinary tract infections, with activity against multidrug resistant uropathogens. The impact of interindividual variability in urinary concentrations on antimicrobial efficacy, and any benefit of giving multiple doses, is uncertain. We therefore performed pharmacodynamic profiling of oral fosfomycin, using a dynamic bladder infection in vitro model, to assess high and low urinary exposures following a single oral dose, and three repeat doses given every 72 h, 48 h and 24 h against 16 clinical isolates with varied MICs of fosfomycin (8 Escherichia coli, 4 Enterobacter cloacae, 4 Klebsiella pneumoniae). Baseline fosfomycin high-level resistant (HLR) subpopulations were detected prior to drug exposure in half of the isolates (2 E. coli, 2 E. cloacae, 4 K. pneumoniae; proportion 1x10-5 – 5x10-4% of total population). Fosfomycin exposures were accurately reproduced compared to mathematical modelling (linear regression slope 1.1, R2 0.99) and bias of 3.8 ± 5.7%. All 5/5 isolates with MICs ≤ 1 μg/mL had no HLR and were killed, whereas 8/11 isolates with higher MICs re-grew regardless of exposure to high or low urinary concentrations. A disk diffusion zone < 24 mm was a better predictor for baseline HLR and regrowth. Administering 3-doses with average exposures provided very limited additional kill. These results suggest that baseline heteroresistance is important for treatment response, while increased drug exposure and administering multiple doses may not be better than standard single dose fosfomycin therapy.
Papenburg J, Alghounaim M.
Human metapneumoviruscommunity-acquired pneumoniadiagnosishospitalizationadultschildren
Ciarlo E, Heinonen T, Théroude C, et al.
AbstractBackgroundThe innate immune system recalls a challenge to adapt to a secondary challenge, a phenomenon called trained immunity. Training involves cellular metabolic, epigenetic and functional reprogramming, but how broadly trained immunity protects from infections is unknown. For the first time, we addressed whether trained immunity provides protection in a large panel of preclinical models of infections.MethodsMice were trained and subjected to systemic infections, peritonitis, enteritis and pneumonia induced by Staphylococcus aureus, Listeria monocytogenes, Escherichia coli, Citrobacter rodentium and Pseudomonas aeruginosa. Bacteria, cytokines, leukocytes and hematopoietic precursors were quantified in blood, bone marrow and organs. The role of monocytes/macrophages, granulocytes and IL-1 signaling was investigated using depletion or blocking approaches.ResultsInduction of trained immunity protected mice in all preclinical models, including when training and infection were initiated in distant organs. Trained immunity increased bone marrow hematopoietic progenitors, blood Ly6Chigh inflammatory monocytes and granulocytes, and sustained blood antimicrobial responses. Monocytes/macrophages and IL-1 signaling were required to protect trained mice from listeriosis. Trained mice were efficiently protected from peritonitis and listeriosis for up to 5 weeks.ConclusionsTrained immunity confers broad-spectrum protection against lethal bacterial infections. These observations support the development of trained immunity-based strategies to improve host defenses.
Varicella-zoster virus (VZV) causes herpes zoster. Pneumocystis jirovecii (PJ) also causes pneumonia in immunocompromised hosts. Although both cause opportunistic infections, it is rare to have a co-infection in a non-human immunodeficiency virus carrier.
An 84-year-old woman with hemolytic anemia referred because of acute respiratory failure. She had received prednisolone without PJ pneumonia prevention. She developed dyspnea and desaturation while eating, and thus was treated based on a presumptive diagnosis of aspiration pneumonia. Physical examination revealed a vesicular rash on the left side of her neck suggesting herpes zoster infection. Polymerase chain reaction of her sputum for PJ and VZV was positive, which confirmed a diagnosis of pneumonia due to PJ and VZV co-infection. Despite acyclovir and sulfamethoxazole and trimethoprim administration, she died on hospital day 19.
Clinicians should suspect PJP when patients on systemic corticosteroids develop pneumonia and they have not received prophylactic treatment for PJP in non-HIV carriers. When such patients have a VZV rash, clinicians should aggressively seek signs of opportunistic infections. Our case hereby highlights the importance of recognizing the possibility of a VZV and PJ co-infection.
Human Immunodeficiency Virus (HIV) infection has become a global concern. Determining the factors leading to death among HIV patients helps controlling Acquired Immune Deficiency Syndrome (AIDS) epidemic. Up to now, little is known about mortality and its determinants among people living with HIV in the Middle East and North Africa (MENA) region, including Iran. The purpose of this study was to assess the risk factors of AIDS-Related Mortality (ARM) and Non-AIDS-Related Mortality (NARM) among people with HIV in Iran.
This 20-year retrospective study was conducted on 1160 people with HIV whose data were collected from 1997 to 2017. The association of the study outcomes (ARM and NARM) with various study variables, including demographic status at the time of diagnosis and clinical indexes during the follow-up were examined to define the predictors of mortality among the patients. Regarding, Cox proportional hazard and competing risk models were fitted and Adjusted Hazard Ratios (AHR), Sub-distribution Hazard Ratio (SHR) and the 95% Confidence Intervals (CI) were reported.
during the follow-up period, 391 individuals (33.7%) died with 86,375 person-years of follow-up. Of the total deaths, 251 (64.2%) and 140 (35.8%) were ARM and NARM, respectively. Rates of the mortality caused by AIDS and non-AIDS were 3.2 and 4.5 per 1000 person-months, respectively. Responding to combined Antiretroviral Treatment (cART) 6 months after initiation, receiving Pneumocystis Pneumonia (PCP) prophylaxis, and higher CD4 count at diagnosis, reduced the hazard of ARM and NARM. However, older age, late HIV diagnosis, and last HIV clinical stages increased the hazard of AIDS related to mortality. Additionally, male gender, older age, incarceration history, and last HIV clinical stages increased the non-AIDS mortality.
Mortality caused by AIDS and non-AIDS remains high among people with HIV in Iran, particularly among males and those with late diagnosis. It seems that applying effective strategies to identify infected individuals at earlier stage of the infection, and targeting individuals with higher risk of mortality can decrease the mortality rate among HIV infected people.
This study investigated predominant microorganisms causing community-onset bacteraemia at the medical emergency department (ED) of a tertiary-care university hospital in Germany from 2013 to 2018 and their antimicrobial susceptibility patterns.
Antimicrobial resistance patterns in patients with positive blood cultures presenting to an internal medicine ED were retrospectively analysed.
Blood cultures were obtained at 5191 of 66,879 ED encounters, with 1013 (19.5%) positive results, and true positive results at 740 encounters (diagnostic yield, 14.3%). The most frequently isolated relevant microorganisms were Enterobacterales (n = 439, 59.3%), Staphylococcus aureus (n = 92, 12.4%), Streptococcus pneumoniae (n = 34, 4.6%), Pseudomonas aeruginosa (n = 32, 4.3%), Streptococcus pyogenes (n = 16, 2.2%), Enterococcus faecalis (n = 18, 2.4%), and Enterococcus faecium (n = 12, 1.6%). Antimicrobial susceptibility testing revealed a high proportion of resistance against ampicillin-sulbactam in Enterobacterales (42.2%). The rate of methicillin-resistant Staphylococcus aureus was low (0.4%).
Piperacillin-tazobactam therapy provided coverage for 83.2% of all relevant pathogens using conventional breakpoints. Application of the new European Committee on Antimicrobial Susceptibility Testing (EUCAST) recommendations increased the percentage of susceptible isolates to high-dose piperacillin-tazobactam to 92.8% (p
To investigate the clinical features of septic pulmonary embolism (SPE) cases and prognostic factors for in-hospital mortality in China.
A retrospective analysis was conducted of SPE patients hospitalized between January 2007 and June 2018 in the Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University.
A total of 98 patients with SPE were identified. All patients had bilateral multiple peripheral nodules on chest computed tomography. The most common pathogen found in blood culture was Staphylococcus aureus (10/33, 30.3%). Transthoracic echocardiography was performed in 39 patients and 20 showed vegetations. Bronchoscopy was performed in 24 patients. Bronchoalveolar lavage fluid (BALF) was obtained from 15 patients (62.5%) and showed predominantly polymorphonuclear cell infiltration (52%, range of 48%~ 63%). Four patients received transbronchial lung biopsy, and histopathological examinations revealed suppurative pneumonia and organizing pneumonia. The in-hospital mortality rate was 19.4%. Age (odds ratio [OR] 1.100; 95% confidence interval [CI] 1.035–1.169), hypotension (OR 7.260; 95% CI 1.126–46.804) and ineffective or delay of empirical antimicrobial therapy (OR 7.341; 95% CI 1.145–47.045) were found to be independent risk factors for in-hospital mortality, whereas drainage treatment was found to be a protective factor (OR 0.33; 95% CI 0.002–0.677).
SPE cases presented with nonspecific clinical manifestations and radiologic features. Blood cultures and bronchoscopy are important measures for early diagnosis and differential diagnosis. There is relationship between primary infection sites and the type of pathogen. Maintaining normal blood pressure and providing timely and appropriate initial antimicrobial therapy for effective control of the infection could improve prognosis.
Dawood F, , Garg S, et al.
AbstractBackgroundPregnant women are at increased risk of seasonal influenza hospitalizations, but data about the epidemiology of severe influenza among pregnant women remain largely limited to pandemics.MethodsTo describe the epidemiology of hospitalizations for acute respiratory infection or febrile illness (ARFI) and influenza-associated ARFI among pregnant women, administrative and electronic health record data were analyzed from retrospective cohorts of pregnant women hospitalized with ARFI who had testing for influenza viruses by RT-PCR in Australia, Canada, Israel and the United States during 2010-2016.ResultsOf 18,048 ARFI-coded hospitalizations, 1,064 (6%) included RT-PCR testing for influenza viruses, of which 614 (58%) were influenza-positive. Of 614 influenza-positive ARFI hospitalizations, 35% were in women with low socioeconomic status, 20% with underlying conditions, and 67% in their third trimesters. The median length of influenza-positive hospitalizations was 2 days (IQR 1-4), 18% (95% confidence interval (CI) 15-21%) resulted in delivery, 10% (95% CI 8-12%) included a pneumonia diagnosis, 5% (95% CI 3-6%) required intensive care, 2% (95% CI 1-3%) included a sepsis diagnosis, and
Community-onset pneumonia (COP) is a combined concept of community acquired pneumonia and the previous classification of healthcare-associated pneumonia. Although ceftriaxone (CRO) is one of the treatment choices for COP, it is unclear whether 1 or 2 g CRO daily has better efficacy. We compared the effectiveness of 1 g with 2 g of CRO for COP treatment. We hypothesized that 1 g CRO would show non-inferiority over 2 g CRO.
This study was an analysis of prospectively registered data of the patients with COP from four Japanese hospitals (the Adult Pneumonia Study Group-Japan: APSG-J). We included subjects who were initially treated solely with 1 or 2 g of CRO. The propensity score was estimated from the 33 pre-treatment variables, including age, sex, weight, pre-existing comorbidities, prescribed drugs, risk factors for aspiration pneumonia, vital signs, laboratory data, and a finding from chest xrays. The primary endpoint was the cure rate, for which a non-inferiority analysis was performed with a margin of 0.05. In addition, we performed three sensitivity analyses; using data limited to the group in which CRO solely was used until the completion of treatment, using data limited to inpatient cases, and performing a generalized linear mixed-effect logistic regression analysis to assess the primary outcome after adjusting for random hospital effects.
Of the 3817 adult subjects with pneumonia who were registered in the APSG-J study, 290 and 216 were initially treated solely with 1 or 2 g of CRO, respectively. Propensity score matching was used to extract 175 subjects in each group. The cure rate was 94.6 and 93.1% in the 1 and 2 g CRO groups, respectively (risk difference 1.5%; 95% confidence interval − 3.1 to 6.0; p = 0.009 for non-inferiority). The results of the sensitivity analyses were consistent with the primary result.
The propensity score-matched analysis of multicenter cohort data from Japan revealed that the cure rate for COP patients treated with 1 g daily CRO was non-inferior to that of patients treated with 2 g daily CRO.
Alamarat, Z. I., Babic, J., Tran, T. T., Wootton, S. H., Dinh, A. Q., Miller, W. R., Hanson, B., Wanger, A., Gary, J. L., Arias, C. A., Perez, N.
We report a 15 year-old Nigerian adolescent male with chronic osteomyelitis caused by extensively drug-resistant (XDR) Pseudomonas aeruginosa ST773 carrying blaNDM-1 and an extended spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae. The patient developed neurological side effects in the form of circumoral paresthesia with polymyxin B and asymptomatic elevation of transaminases with aztreonam (used in combination with ceftazidime/avibactam). Cefiderocol treatment for 14 weeks plus bone implant resulted in apparent cure and avoided amputation.
Sharara S, Amoah J, Pana Z, et al.
AbstractBackgroundLimited data exist regarding the efficacy of piperacillin-tazobactam (TZP) for the management of non-bacteremic pyelonephritis caused by ESBL-producing organisms.MethodsWe conducted a multicenter observational study comparing clinical outcomes in adults hospitalized with ESBL-producing pyelonephritis receiving TZP versus carbapenems using an inverse probability of treatment weighted propensity score analysis. Patients were eligible for inclusion if all of the following criteria were met: (1) urine cultures growing Escherichia coli, Klebsiella pneumoniae, K. oxytoca, or Proteus mirabilis at ≥50,000 CFU/mL, (2) identification of an ESBL gene by uropathogen; (3) pyuria (≥10 WBC/hpf); and (4) dysuria and fever plus at least one of the following symptoms: emesis, rigors, hypotension, or flank pain.Results186 patients were included in the propensity-score weighted cohort; 45 (24%) received TZP and 141 (76%) received a carbapenem. 27% of patients were admitted to the ICU, 47% were immunocompromised, and 46% of patients had underlying urologic abnormalities. There were no differences between the two groups in the proportion of patients (20% vs. 25%) with recurrent cystitis or pyelonephritis with the same ESBL-producing organism within 30 days (OR 0.75; 95% CI 0.31-1.81, p=0.52). There were no differences in resolution of clinical symptoms by day 7 or 30-day mortality. One (2%) patient in the TZP arm and 11 (8%) patients in the carbapenem arm had incident carbapenem-resistant organisms isolated within 60 days (p=0.09).ConclusionTZP may be a reasonable alternative to carbapenems for the management of ESBL-producing pyelonephritis and may mitigate the risk of emergence of carbapenem-resistant organisms, compared with carbapenem therapy.
Lopamudra Ray Saraswati,
Punit Kumar Mishra,
Tropical Medicine &International Health, Volume 0, Issue ja, -Not available-.
Klebsiella species are among the most common causes of bloodstream infection (BSI). However, few studies have evaluated their epidemiology in non-selected populations. The objective was to define the incidence of, risk factors for, and outcomes from Klebsiella species BSI among residents of the western interior of British Columbia, Canada.
Population-based surveillance was conducted between April 1, 2010 and March 31, 2017.
151 episodes were identified for an incidence of 12.1 per 100,000 population per year; the incidences of K. pneumoniae and K. oxytoca were 9.1 and 2.9 per 100,000 per year, respectively. Overall 24 (16%) were hospital-onset, 90 (60%) were healthcare-associated, and 37 (25%) were community-associated. The median patient age was 71.4 (interquartile range, 58.8–80.9) years and 88 (58%) cases were males. Episodes were uncommon among patients aged < 40 years old and no cases were observed among those aged < 10 years. A number of co-morbid medical illnesses were identified as significant risks and included (incidence rate ratio; 95% confidence interval) cerebrovascular accident (5.9; 3.3–9.9), renal disease 4.3; 2.5–7.0), cancer (3.8; 2.6–5.5), congestive heart failure (3.5; 1.6–6.6), dementia (2.9; 1.5–5.2), diabetes mellitus (2.6; 1.7–3.9), and chronic obstructive pulmonary disease (2.3; 1.5–3.5). Of the 141 (93%) patients admitted to hospital, the median hospital length stay was 8 days (interquartile range, 4–17). The in-hospital and 30-day all cause case-fatality rates were 24/141 (17%) and 27/151 (18%), respectively.
Klebsiella species BSI is associated with a significant burden of illness particularly among those with chronic co-morbid illnesses.
Daniel A Sweeney, Andre C Kalil
Pneumonia is the most common and serious hospital-acquired infection worldwide, and ventilator-associated pneumonia (VAP) comprises 40% of these cases.1 Management of VAP caused by difficult-to-treat organisms remains problematic. The Infectious Diseases Society of America and American Thoracic Society (IDSA/ATS) guidelines1 for hospital-acquired pneumonia and VAP suggest that VAP due to Gram-negative bacilli that are susceptible to only aminoglycosides or polymyxins should be treated with both inhaled and intravenous antibiotics.
Michael S Niederman, Jeff Alder, Matteo Bassetti, Francis Boateng, Bin Cao, Kevin Corkery, Rajiv Dhand, Keith S Kaye, Robert Lawatscheck, Patrick McLeroth, David P Nicolau, Chen Wang, G Christopher Wood, Richard G Wunderink, Jean Chastre
Our findings do not support use of inhaled amikacin adjunctive to standard-of-care intravenous therapy in mechanically ventilated patients with Gram-negative pneumonia.
Blot M, Chavanet P, Piroth L.
To the Editor—We read with interest the article titled “Procalcitonin to distinguish viral from bacterial pneumonia: a systematic review and meta-analysis” . The frequent lack of a microbiological diagnosis in pneumonia impairs pathogen-directed antimicrobial therapy. New tools to distinguish viral from bacterial pneumonia are urgently needed to implement antibiotic stewardship. Kamat et al showed that serum procalcitonin (PCT) levels are neither sufficiently specific nor sensitive to distinguish bacterial from viral pneumonia . However, several caveats and limitations must be pointed out.
Kamat I, Ramachandran V, Eswaran H, et al.
To the Editor—As Blot et al  correctly reference, there is a paucity of data that reports the sensitivity and/or specificity for procalcitonin in the diagnosis of community-acquired pneumonia. Similarly, Peacock and Rafique  indicated that further refinement of the procalcitonin assay is needed, indicating that 2 cut points with an indeterminate range would be more helpful to the clinician than a single cut point. Our study, however, was a meta-analysis, and our capacity to perform statistical analyses was dependent upon the data that were reported. We simply did not have sufficient data to use 2 cut-off points and indicate an indeterminate range, and we acknowledge the limitations of conventional, noninvasive, microbiological diagnostic methods.
Peacock W, Rafique Z.
To the Editor—Dr Kamat et al  performed a nice evaluation of the existing procalcitonin literature, showing that receiver operator characteristic curve-derived cut points for the prediction of bacterial pneumonia are neither sensitive nor specific. While a common strategy, a single, dichotomous cut point does not embody human physiology; hence, it is an unfair measure of procalcitonin’s utility in clinical decision-making.
McCurdy, S., Keedy, K., Lawrence, L., Nenninger, A., Sheets, A., Quintas, M., Cammarata, S.
Delafloxacin is a novel fluoroquinolone with activity against Gram-positive, Gram-negative and atypical pathogens, including fluoroquinolone non-susceptible MRSA. The microbiological results of a phase 3 clinical trial in community acquired pneumonia comparing delafloxacin [300 mg IV with option to switch to 450 mg orally every 12h to moxifloxacin 400 mg IV with option to switch to 400 mg orally QD] were determined. Patients from 4 continents, predominately Europe but also South America, and Asia, were enrolled. The microbiological intent-to-treat (MITT) population included 520 patients and 60.5% of these patients had a bacterial pathogen identified. Multiple diagnostic methods were employed including culture, serology, PCR, and urinary antigen. Based on baseline MIC90 values, delafloxacin exhibited at least 16-fold greater activity than moxifloxacin for Gram-positive and fastidious Gram-negative pathogens. Delafloxacin retained activity against resistant phenotypes found in S. pneumoniae (penicillin-, macrolide-, multiple-drug resistant), Haemophilus species (β-lactamase producing, macrolide-non-susceptible) and S. aureus (MRSA, fluoroquinolone-non-susceptible MSSA). The microbiological success rates were: 92.7% for S. pneumoniae (87.5% for PRSP), 92.6% for S. aureus (100% for MRSA), 100% for E. coli, 82.4% for K. pneumoniae, 100% for K. oxytoca, 100% for M. catarrhalis, 91.7% for H. influenzae, 88.6% for H. parainfluenzae, 96.7% for M. pneumoniae, 93.1% for L. pneumophila, and 100% for C. pneumoniae. There was little correlation between MIC and outcome with a high proportion of favorable outcomes observed across all delafloxacin baseline MIC values. Delafloxacin may be considered a treatment option as monotherapy for CAP in adults, where broad spectrum coverage including MRSA activity is desirable.
Vu, T. T. T., Nguyen, N. T. Q., Tran, V. G., Gras, E., Mao, Y., Jung, D. H., Tkaczyk, C., Sellman, B. R., Diep, B. A.
Staphylococcus aureus is a major human pathogen, causing a wide range of infections by producing an arsenal of cytotoxins. We found that passive immunization with either a monoclonal antibody (mAb) neutralizing alpha-hemolysin or a broadly cross-reactive mAb that neutralize Panton-Valentine leukocidin, leukocidin ED and gamma-hemolysins HlgAB/HlgCB only conferred partial protection, whereas the combination of those two mAbs conferred significant protection in a rabbit model of necrotizing pneumonia caused by the USA300 MRSA epidemic clone.
Morrissey, I., Hawser, S., Lob, S. H., Karlowsky, J. A., Bassetti, M., Corey, G. R., Olesky, M., Newman, J., Fyfe, C.
Eravacycline is a novel, fully-synthetic fluorocycline antibiotic being developed for the treatment of serious infections, including those caused by resistant Gram-positive pathogens. Herein, we evaluated the in vitro activities of eravacycline and comparator antimicrobial agents against a recent global collection of frequently encountered clinical isolates of Gram-positive bacteria. The CLSI broth microdilution method was used to determine in vitro MIC data for isolates of Enterococcus spp. (n=2,807), Staphylococcus spp. (n=4,331), and Streptococcus spp. (n=3,373) isolated primarily from respiratory, intra-abdominal, urinary, and skin specimens by clinical laboratories in 37 countries on three continents from 2013 to 2017. Susceptibilities were interpreted using both CLSI and EUCAST breakpoints. There were no substantive differences (>1 doubling increase or decrease) in eravacycline MIC90 values for different species/organism groups over time or by region. Eravacycline showed MIC50 and MIC90 results of 0.06 and 0.12 μg/ml when tested against Staphylococcus aureus, regardless of methicillin susceptibility. Staphylococcus epidermidis and Staphylococcus haemolyticus demonstrated equal MIC90 values for eravacycline (0.5 μg/ml). The eravacycline MIC90s for Enterococcus faecalis and Enterococcus faecium were 0.06 μg/ml, and were within one doubling-dilution regardless of vancomycin susceptibility profile. Eravacycline exhibited MIC90 results of ≤0.06 μg/ml when tested against Streptococcus pneumoniae, β-hemolytic, and viridans group streptococci isolates. In this surveillance study eravacycline demonstrated potent in vitro activity against frequently isolated clinical isolates of Gram-positive bacteria (Enterococcus, Staphylococcus, and Streptococcus spp.), including isolates collected over a 5-year period (2013-2017), underscoring its potential benefit in treatment of infections caused by common Gram-positive pathogens.
Zimmerman, S. M., Lafontaine, A.-A. J., Herrera, C. M., Mclean, A. B., Trent, M. S.
The threat of diminished antibiotic discovery has global healthcare in crisis. In the United States, it is estimated each year that over 2 million bacterial infections are resistant to first-line antibiotic treatments and cost in excess of 20 billion dollars. Many of these cases result from infection with the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter sp.), which are multidrug-resistant bacteria that often cause community- and hospital-acquired infections in both healthy and immunocompromised patients. Physicians have turned to last-resort antibiotics like polymyxins to tackle these pathogens, and as a consequence, polymyxin-resistance has emerged and is spreading. Barring the discovery of new antibiotics, another route to successfully mitigate polymyxin-resistance is to identify compounds that can complement the existing arsenal of antibiotics. We recently designed and performed a large-scale robotic screen to identify 43 bioactive compounds that act synergistically with polymyxin B to inhibit growth of polymyxin-resistant Escherichia coli. Of these 43 compounds, 5 lead compounds were identified and characterized using various Gram-negative bacterial organisms to better assess their synergistic activity with polymyxin. Several of these compounds reduce polymyxin to a minimal inhibitory concentration (MIC) < 2 μg/mL against polymyxin-resistant and polymyxin-heteroresistant Gram-negative pathogens. Likewise, 4 of these compounds exhibit antimicrobial activity against Gram-positive bacteria, one of which rapidly eradicated methicillin-resistant Staphylococcus aureus (MRSA). We present multiple first-generation compounds that warrant further investigation and optimization, as they can act both synergistically with polymyxin and also as lone antimicrobials for combating ESKAPE pathogens.
Specialespecifikt kursus om immundefekt og feber af ukendt årsag
28.01.2020 - 29.01.2020
International Congress on Infectious Diseases (ICID) 2020
Kuala Lumpur, Malaysia
20.02.2020 - 23.02.2020
Dansk Selskab for Intern Medicin (DSIM) årsmøde og overrækkelse af Hagedorn prisen 2020
Novo Nordisk Fonden, Tuborg Havnevej 19, 2900 Hellerup
Conference on Retroviruses and Opportunistic Infections (CROI) 2020
Boston, Massachusetts, USA
8.03.2020 - 11.03.2020
Når CROI går i fisk - med transmissioner fra CROI 2020
10.03.2020 - 11.03.2020
Retningslinjer til sundhedsprofessionelle vedr. håndtering af infektion med zikavirus (2019)
Antiviral behandling af hiv smittede personer (2019)
Lumbalpunktur af patienter i blodfortyndende behandling (2019)
Widening the lens to ensure children who are HIV exposed are alive, HIV-free and thriving
24.01.2020Clinical Infectious Diseases Advance Access
Mortality, HIV transmission and growth in children exposed to HIV in rural Zimbabwe
24.01.2020Clinical Infectious Diseases Advance Access
RSV Antivirals: Problems and Progress
24.01.2020The Journal of Infectious Diseases Advance Access
Efficacy and safety of ceftolozane/tazobactam as therapeutic option for complicated skin and soft tissue infections by MDR/XDR Pseudomonas aeruginosa in patients with impaired renal function: a case series from a single-center experience
24.01.2020Latest Results for Infection
How to Choose Target Facilities in a Region to Implement Carbapenem-Resistant Enterobacteriaceae (CRE) Control Measures
23.01.2020Clinical Infectious Diseases Advance Access
Hvad tænker Professor Jens Lundgren om"Dolutegravir plus Two Different Prodrugs of Tenofovir to Treat HIV."?
Hvad synes Professor Troels Lillebæk om"The global prevalence of latent tuberculosis: a systematic review and meta-analysis."?
Hvad synes Professor Lars Østergaard om"Efficacy of antibiotic treatment in patients with chronic low back pain and Modic changes (the AIM study): double blind, randomised, placebo controlled, multicentre trial."?
Hvad tænker Professor Thomas Benfield om"Oral versus Intravenous Antibiotics for Bone and Joint Infection."?
Hvad synes Professor Niels Obel om"Early, Goal-Directed Therapy for Septic Shock - A Patient-Level Meta-Analysis."?
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