Community-acquired Respiratory Infections Research Articles

1041. In vitro activity of tebipenem against a recent collection of fastidious organisms recovered from respiratory tract infections

BackgroundTebipenem is under development as an oral treatment option for complicated urinary tract infections and acute pyelonephritis. This study further evaluated the in vitro activity of tebipenem against various fastidious organisms recovered from community-acquired respiratory tract infections (CARTIs).MethodsThe study included a total of 2,476 fastidious organisms: Haemophilus influenzae (692 isolates, including fluoroquinolone-resistant, β-lactamase-positive, and β-lactamase-negative ampicillin-resistant [BLNAR]), Haemophilus parainfluenzae (30 isolates, including β-lactamase-positive and BLNAR), Moraxella catarrhalis (490 isolates), and Streptococcus pneumoniae (1,264 isolates, including penicillin-resistant). The isolates were collected primarily from CARTIs (90.8%) and pneumonia in hospitalized patients (PIHPs, 9.2%). Organisms were tested using reference broth microdilution methods in a central laboratory. ResultsTebipenem had MIC90 values of 0.5 mg/L against H. influenzae and 1 mg/L against H. parainfluenzae isolates. All 18 BLNAR isolates from these two species were inhibited at ≤1 mg/L of tebipenem. The MIC90 values observed for ertapenem and meropenem was 0.25 mg/L for these organisms. Tebipenem displayed good activity against M. catarrhalis (MIC90, 0.03 mg/L). Tebipenem inhibited 100% of S. pneumoniae isolates at ≤1 mg/L. Tebipenem activity (MIC90, 0.12 mg/L) was 8-fold greater than ertapenem (MIC90, 1 mg/L) against S. pneumoniae isolates.ConclusionTebipenem displayed potent activity against fastidious organisms causing respiratory tract infections. Greater than 99.7% of all Haemophilus isolates, including all BLNAR, were inhibited at ≤1 mg/L. All M. catarrhalis isolates were inhibited at ≤0.03 mg/L. Although tebipenem activity correlated with penicillin resistance, all S. pneumoniae isolates were inhibited at ≤1 mg/L. Tebipenem in vitro activity was greater than ertapenem when tested against S. pneumoniae isolates. This data supports the possible development of tebipenem as an oral option for combating CARTIs caused by these organisms.Table Disclosures S J Ryan Arends, PhD, AbbVie (formerly Allergan) (Research Grant or Support)GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Abby L. Klauer, n/a, Cidara Therapeutics, Inc. (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Nicole Cotroneo, Spero Therapeutics (Employee, Shareholder) Ian A. Critchley, Ph.D., Spero Therapeutics (Employee, Shareholder) Rodrigo E. Mendes, PhD, AbbVie (Research Grant or Support)AbbVie (formerly Allergan) (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)ContraFect Corporation (Research Grant or Support)GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support)

1271. In vitro Activities of Ceftaroline and Comparator Agents Against Bacterial Pathogens Frequently Causing Community-Acquired Respiratory Tract Infections in Patients from a Global Population: ATLAS Surveillance Program 2016-2019

Abstract Background Community-acquired bacterial pneumonia (CABP) is a frequent cause of patient morbidity and mortality. Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis are frequent etiologic agents of CABP. Ceftaroline fosamil is a parenteral cephem approved for treatment of patients with CABP caused by S. pneumoniae (including cases with concurrent bacteremia), methicillin-susceptible Staphylococcus aureus (MSSA), H. influenzae, and some species of Enterobacterales. In this study we report the in vitro activity of ceftaroline and comparators against isolates from community-acquired respiratory tract infections (CARTI) collected through a global surveillance program. Methods Clinically relevant, non-duplicate, isolates cultured from respiratory specimens by clinical laboratories in 54 countries in 2016-2019 were collected by the ATLAS Surveillance Program central laboratory (IHMA, Schaumburg, IL, USA). In total, 2,636 isolates of S. pneumoniae, H. influenzae, M. catarrhalis, MSSA, and methicillin-resistant S. aureus (MRSA) were tested. The isolates (n/percent of total) originated from Asia/South Pacific (722/27.4%); Europe (1481/56.2%); Latin America (292/11.1%); Middle East/Africa (57/2.2%); and North America (Canada only) (84/3.2%). Ceftaroline and comparator agent MICs were determined by CLSI M07 broth microdilution methodology. MICs were interpreted using 2021 CLSI M100 MIC breakpoints. Results Ceftaroline and comparator agent in vitro activities are summarized in the table. Greater than 98% of S. pneumoniae and >99% of MSSA were susceptible to ceftaroline, including penicillin-nonsusceptible S. pneumoniae based on a dosage of 600 mg every 12h. Sixty-four (24.4%) MRSA were ceftaroline-susceptible-dose-dependent (MIC 2-4 µg/mL) based on a dosage of 600 mg every 8h administered over 2h, with the majority from (n) China (70), S. Korea (19), Japan (10), and Chile (8). Three isolates, all from China, were resistant to CPT (MIC of 8 µg/mL). 99.2% of H. influenzae were susceptible to ceftaroline. Results Table Conclusion Ceftaroline demonstrated potent in vitro activity against current pathogens associated with CABP from a global collection. Disclosures Meredith Hackel, PhD MPH, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Gregory Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)

155. In Vitro Evaluation of Delafloxacin Activity Against Contemporary US Isolates from Community-Acquired Pneumonia and Community-Acquired Lower Respiratory Tract Infections: Results from the SENTRY Antimicrobial Surveillance Program (2014-2020)

155. <i>In Vitro</i> Evaluation of Delafloxacin Activity Against Contemporary US Isolates from Community-Acquired Pneumonia and Community-Acquired Lower Respiratory Tract Infections: Results from the SENTRY Antimicrobial Surveillance Program (2014-2020)

Cephalosporin in the management of children with acute otitis media

Background: Acute otitis media (AOM) is a community-acquired respiratory tract infection in childhood frequently encountered by primary-care physicians and can cause a significant morbidity. Increasing bacterial resistance has led to concern about the current options for empirical antibiotic treatment and has prompted a search for effective treatments. Objectives: To evaluate the clinical efficacy and safety of cefpodoxime proxetil in the treatment of children with acute otitis media. Patients and methods: A prospective, multicenter study was conducted on 1380 children aged from 1 to 13 years with AOM who were prescribed a 5–10 day course of cefpodoxime proxetil (8 mg/kg/day). Patients were followed-up after 7–14 days from baseline visit. Efficacy was assessed by the percentage of patients with clinical cure, improvement or failure at the follow-up visit. Safety was evaluated by recording the occurrence and severity of any adverse events and by the physicians’ and patients’ assessment of overall tolerability. Results: Clinically, 82.5% of patients were cured, 16.4% were improved and there was failure of therapy in 1.1% of the patients. The overall combined cure and improvement rate of all related signs and symptoms was 98.9%. Adverse events, diarrhea and skin rash, were reported by only 16 patients (1.2%).

Role of cefpodoxime in the treatment of ear infections

Background: Acute otitis media (AOM) is a community-acquired respiratory tract infection in childhood frequently encountered by primary-care physicians and can cause a significant morbidity. Increasing bacterial resistance has led to concern about the current options for empirical antibiotic treatment and has prompted a search for effective treatments. Objectives: To evaluate the clinical efficacy and safety of cefpodoxime proxetil in the treatment of children with acute otitis media. Patients and methods: A prospective, multicenter study was conducted on 1380 children aged from 1 to 13 years with AOM who were prescribed a 5–10 day course of cefpodoxime proxetil (8 mg/kg/day). Patients were followed-up after 7–14 days from baseline visit. Efficacy was assessed by the percentage of patients with clinical cure, improvement or failure at the follow-up visit. Safety was evaluated by recording the occurrence and severity of any adverse events and by the physicians’ and patients’ assessment of overall tolerability. Results: Clinically, 82.5% of patients were cured, 16.4% were improved and there was failure of therapy in 1.1% of the patients. The overall combined cure and improvement rate of all related signs and symptoms was 98.9%. Adverse events, diarrhea and skin rash, were reported by only 16 patients (1.2%).

Role of cefpodoxime in the treatment of ear infections

Background: Acute otitis media (AOM) is a community-acquired respiratory tract infection in childhood frequently encountered by primary-care physicians and can cause a significant morbidity. Increasing bacterial resistance has led to concern about the current options for empirical antibiotic treatment and has prompted a search for effective treatments. Objectives: To evaluate the clinical efficacy and safety of cefpodoxime proxetil in the treatment of children with acute otitis media. Patients and methods: A prospective, multicenter study was conducted on 1380 children aged from 1 to 13 years with AOM who were prescribed a 5–10 day course of cefpodoxime proxetil (8 mg/kg/day). Patients were followed-up after 7–14 days from baseline visit. Efficacy was assessed by the percentage of patients with clinical cure, improvement or failure at the follow-up visit. Safety was evaluated by recording the occurrence and severity of any adverse events and by the physicians’ and patients’ assessment of overall tolerability. Results: Clinically, 82.5% of patients were cured, 16.4% were improved and there was failure of therapy in 1.1% of the patients. The overall combined cure and improvement rate of all related signs and symptoms was 98.9%. Adverse events, diarrhea and skin rash, were reported by only 16 patients (1.2%).

IL-17 stimulates neutrophils to release S100A8/A9 to promote lung epithelial cell apoptosis in Mycoplasma pneumoniae–induced pneumonia in children

Mycoplasma pneumoniae-induced pneumonia (MPP) is a common cause of community-acquired respiratory tract infections, increasing risk of morbidity and mortality, in children. However, diagnosing early-stage MPP is difficult owing to the lack of good diagnostic methods. Here, we examined the protein profile of bronchoalveolar lavage fluid (BALF) and found that S100A8/A9 was highly expressed. Enzyme-linked immunosorbent assays used to assess protein levels in serum samples indicated that S100A8/A9 concentrations were also increased in serum obtained from children with MPP, with no change in S100A8/A9 levels in children with viral or bacterial pneumonia. In vitro, S100A8/A9 treatment significantly increased apoptosis in a human alveolar basal epithelial cell line (A549 cells). Bioinformatics analyses indicated that up-regulated S100A8/A9 proteins participated in the interleukin (IL)−17 signaling pathway. The origin of the increased S100A8/A9 was investigated in A549 cells and in neutrophils obtained from children with MPP. Treatment of neutrophils, but not of A549 cells, with IL-17A released S100A8/A9 into the culture medium. In summary, we demonstrated that S100A8/A9, possibly released from neutrophils, is a new potential biomarker for the clinical diagnosis of children MPP and involved in the development of this disease through enhancing apoptosis of alveolar basal epithelial cells.

Retraction Note to: Childhood nosocomial viral acute respiratory tract infections in teaching hospital Anuradhapura, Sri Lanka

We have assessed the risk factors for the occurrence of hospital-acquired (HA) and community-acquired (CA) viral acute respiratory tract infections (ARTIs) in children. Children (1–60 months) who were having ARTI on admission (CA) and develops ARTI following 48 h after admission or 3 days of discharge (HA) were included. Indirect immunofluorescence assay (IFA) was performed and multivariable analyses were done to determine the risk factors for the development of viral CA and HA-ARTI. Total of 818 with ARTIs, 226 (27.6%) RSV cases were detected. Out of 226, 86 (38.0%) HA-RSV cases were detected. CA-viral-ARTI was significantly high (p < 0.05). Compared to CA-RSV-ARTI immunodeficiency, seizures, trisomy-21 and congenital heart disease (CHD) were having 2.3, 3.2, 1.8- and 2.2-times risk for acquiring HA-RSV respectively. The number of deaths was significantly high following HA-RSV. The associated burden was significant following HA-RSV and it was 429.77 disability-adjusted life years. Children who are having immunodeficiency, CHD, seizure episodes and trisomy 21 would lead to the acquisition of nosocomial RSV infections in great. Adherence to meticulous infection control practices will be helpful to minimize the HA-viral ARTIs in great.

Advances in the Microbiology of Stenotrophomonas maltophilia.

Stenotrophomonas maltophilia is an opportunistic pathogen of significant concern to susceptible patient populations. This pathogen can cause nosocomial and community-acquired respiratory and bloodstream infections and various other infections in humans. Sources include water, plant rhizospheres, animals, and foods. Studies of the genetic heterogeneity of S. maltophilia strains have identified several new genogroups and suggested adaptation of this pathogen to its habitats. The mechanisms used by S. maltophilia during pathogenesis continue to be uncovered and explored. S. maltophilia virulence factors include use of motility, biofilm formation, iron acquisition mechanisms, outer membrane components, protein secretion systems, extracellular enzymes, and antimicrobial resistance mechanisms. S. maltophilia is intrinsically drug resistant to an array of different antibiotics and uses a broad arsenal to protect itself against antimicrobials. Surveillance studies have recorded increases in drug resistance for S. maltophilia, prompting new strategies to be developed against this opportunist. The interactions of this environmental bacterium with other microorganisms are being elucidated. S. maltophilia and its products have applications in biotechnology, including agriculture, biocontrol, and bioremediation.

Community-Acquired Respiratory Viruses Post–Lung Transplant

Survival in lung transplant recipients (LTRs) lags behind heart, liver, and kidney transplant, in part due to the direct and indirect effects of infection. LTRs have increased susceptibility to infection due to the combination of a graft continually exposed to the outside world, multiple mechanisms for impaired mucus clearance, and immunosuppression. Community-acquired respiratory viral infections (CARVs) are common in LTRs. Picornaviruses have roughly 40% cumulative incidence followed by respiratory syncytial virus and coronaviruses. Although single-center retrospective and prospective series implicate CARV in rejection and mortality, conclusive evidence for and well-defined mechanistic links to long-term outcome are lacking. Treatment of viral infections can be challenging except for influenza. Future studies are needed to develop better treatments and clarify the links between CARV and long-term outcomes.

Community-acquired lower respiratory tract infections in an adult population with HIV infection in a Nigerian tertiary hospital

Objective: Lower respiratory tract infections (LRTI) are 25-fold more common in people with HIV than in the general population. This study aimed to determine the prevalence of community-acquired LRTI and its associated factors in an adult population of people living with HIV (PLWH) in a Nigerian tertiary Hospital.Methodology: This was a prospective study done at the HIV clinic of Ladoke Akintola University of Technology (LAUTECH) Teaching Hospital Osogbo, Nigeria. It involved 130 randomly selected adult participants with a confirmed HIV-positive serology. The participants were followed up for a period of one year while looking out for symptoms and signs suggestive of LRTI.Results: The participants had a mean age of 41.9±10.02 years and a male to female ratio of 0.4:1. Seventeen (13.9%) of the participants developed LRTI during the study period and this was significantly associated with CD4 count and cigarette smoking history.Conclusion: LRTI is common among PLWH in Osogbo, and it occurs more commonly in those with low CD4 Tcell count and those with a history of cigarette smoking.&#x0D; Keywords: Lower respiratory tract infection, HIV, pneumonia.

Incidence, risk factors, and viral etiology of community-acquired acute lower respiratory tract infection among older adults in rural north India.

BackgroundThere are limited data on incidence, risk factors and etiology of acute lower respiratory tract infection (LRTI) among older adults in low- and middle-income countries.MethodsWe established a cohort of community dwelling older adults ≥60 years and conducted weekly follow-up for acute respiratory infections (ARI) during 2015-2017. Nurses assessed ARI cases for LRTI, collecting combined nasal/throat swabs from all LRTI cases and an equal number of age- and sex-matched asymptomatic neighbourhood controls. Swabs were tested for influenza viruses, respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and parainfluenza viruses (PIV) using polymerase chain reaction. LRTI and virus-specific LRTI incidence was calculated per 1000 person-years. We estimated adjusted incidence rate ratios (IRR) for risk factors using Poisson regression and calculated etiologic fractions (EF) using adjusted odds ratios for detection of viral pathogens in LRTI cases vs controls.ResultsWe followed 1403 older adults for 2441 person-years. LRTI and LRTI-associated hospitalization incidences were 248.3 (95% confidence interval (CI) = 229.3-268.8) and 12.7 (95% CI = 8.9-18.1) per 1000 person-years. Persons with pre-existing chronic bronchitis as compared to those without (incidence rate ratio (IRR) = 4.7, 95% CI = 3.9-5.6); aged 65-74 years (IRR = 1.6, 95% CI = 1.3-2.0) and ≥75 years (IRR = 1.8, 95% CI = 1.4-2.4) as compared to 60-64 years; and persons in poorest wealth quintile (IRR = 1.4, 95% CI = 1.1-1.8); as compared to those in wealthiest quintile were at higher risk for LRTI. Virus was detected in 10.1% of LRTI cases, most commonly influenza (3.8%) and RSV (3.0%). EF for RSV and influenza virus was 83.9% and 83.6%, respectively.ConclusionIn this rural cohort of older adults, the incidence of LRTI was substantial. Chronic bronchitis was an important risk factor; influenza virus and RSV were major viral pathogens.

Comparison of common acute respiratory infection case definitions for identification of hospitalized influenza cases at a population-based surveillance site in Egypt.

BackgroundMultiple case definitions are used to identify hospitalized patients with community-acquired acute respiratory infections (ARI). We evaluated several commonly used hospitalized ARI case definitions to identify influenza cases.MethodsThe study included all patients from a population-based surveillance site in Damanhour, Egypt hospitalized for a broad set of criteria consistent with community acquired ARIs. Naso- and oropharyngeal (NP/OP) swabs were tested for influenza using RT-PCR. Sensitivity, specificity and PPV for influenza identification was compared between the 2014 WHO Severe Acute Respiratory Infection (SARI) definition (fever ≥38°C and cough with onset within 10 days), the 2011 WHO SARI definition (fever ≥38°C and cough with onset within 7 days), the 2006 PAHO SARI definition, the International Emerging Infections Program (IEIP) pneumonia case definition, and the International Management of Childhood Illness (IMCI) case definitions for moderate and severe pneumonia.ResultsFrom June 2009-December 2012, 5768 NP/OP swabs were obtained from 6113 hospitalized ARI patients; 799 (13.9%) were influenza positive. The 2014 WHO SARI case definition captured the greatest number of ARI patients, influenza positive patients and ARI deaths compared to the other case definitions examined. Sensitivity for influenza detection was highest for the 2014 WHO SARI definition with 88.6%, compared to the 2011 WHO SARI (78.2%) the 2006 PAHO SARI (15.8%) the IEIP pneumonia (61.0%) and the IMCI moderate and severe pneumonia (33.8% and 38.9%) case definitions (IMCI applies to <5 only).ConclusionsOur results support use of the 2014 WHO SARI definition for identifying influenza positive hospitalized SARI cases as it captures the highest proportion of ARI deaths and influenza positive cases. Routine use of this case definition for hospital-based surveillance will provide a solid, globally comparable foundation on which to build needed response efforts for novel pandemic viruses.

Evaluation of a novel immunochromatographic assay using silver amplification technology for detection of Mycoplasma pneumoniae from throat swab samples in pediatric patients

Abstract Objectives Mycoplasma pneumoniae is one of the common causative pathogens of community-acquired respiratory tract infections mainly in children and young adults. Rapid and accurate diagnostic techniques for identifying the causative pathogen would be useful for initiating treatment with an appropriate antibiotic. The purpose of the present study was to evaluate the sensitivity and specificity of a novel immunochromatographic assay using silver amplification technology using FUJI DRI-CHEM IMMUNO AG2 and FUJI DRI-CHEM IMMUNO AG cartridge Myco (FUJIFILM Co., Tokyo, Japan) for detection of M. pneumoniae. Methods Throat swab samples were collected from 170 pediatric patients who were diagnosed with bronchitis or pneumonia. The silver amplification immunochromatographic (SAI) assay was performed using these samples and the results were compared with those of real-time PCR. The time required for the SAI assay is approximately 20 min (5 min for sample preparation and 15 min for waiting time after starting the assay). Results The sensitivity and specificity of the SAI assay for detection of M. pneumoniae were 85.2 and 99.1%, respectively, and the assay showed positive and negative predictive values of 98.1 and 92.3%, respectively, compared with the results of real-time PCR. The diagnostic accuracy was 94.1%. Conclusions FUJI DRI-CHEM IMMUNO AG2 and FUJI DRI-CHEM IMMUNO AG cartridge Myco are appropriate for clinical use. The optimal timing of this assay is five days or more after the onset of M. pneumoniae infection. However, PCR or other molecular methods are superior, especially with regard to sensitivity and negative predictive value.

Maxing Shigan Decoction Mitigates Mycoplasma pneumonia-Induced Pyroptosis in A549 Cells via the NLRP3 Inflammasome.

BackgroundMycoplasma pneumoniae is a predominant cause of community-acquired respiratory infections. We recently discovered the clinical efficacy of Maxing shigan decoction (MXSG) in M. pneumoniae infection and designed a study to explore the mechanism of action.MethodsSerum IL-1β, IL-18, and TNF-α, and transcript expression of the NLR Family, Pyrin Domain Containing Protein 3 (NLRP3) were measured in the peripheral blood mononuclear cells (PBMCs) of 30 children with M. pneumoniae infection and 30 healthy donors. An in vitro model of M. pneumoniae infection in A549 cell culture was used to explore the curative effects and mechanisms of MXSG. Pyroptosis was measured by flow cytometry with activated caspase-1 and propidium iodide staining. IL-1β, IL-18, and TNF-α, and NLRP3 transcript expression were measured by qRT-PCR. Protein expression of NLRP3, Caspase-1, pro-caspase-1, IL-1β, pro-IL-1β, and GSDMD-N was determined by Western blotting. Experimental confirmation was performed in NLRP3-overexpressing A549 cells and in the presence of an NLRP3 inhibitor, INF39.ResultsM. pneumoniae infection-induced IL-1β, IL-18, TNF-α, and mRNA expression of NLRP3 in PBMCs and promoted pyroptosis in A549 cells. It also induced IL-1β, IL-18, TNF-α, and up-regulated NLRP3, ro-IL-1β, Caspase-1, Pro-Caspase-1, and GSDMD-N in culture. Similar to the NLRP3 inhibitor INF39, MXSG (0.1, 0.2, and 0.4 mg/mL) suppressed pyroptosis induced by M. pneumoniae infection and decreased IL-1β (P < 0.001), IL-18, TNF-α in culture. MXSG down-regulated NLRP3, pro-IL-1β, Caspase-1, pro-Caspase-1, and GSDMD-N in infected cultures and mitigated NLRP3 overexpression-induced pyroptosis.ConclusionMXSG mitigates M. pneumoniae-induced pyroptosis in A549 cells via the NLRP3 inflammasome.

The impact of COVID-19 lockdown on infectious diseases epidemiology: The experience of a tertiary Italian Pediatric Emergency Department.

IntroductionThe aim of this study was to describe the rate and types of community-acquired respiratory infections observed in a pediatric ED during the SARS-CoV-2 related lockdown in Italy and to compare data with the same period of previous year.MethodsA retrospective analysis of medical charts of patients arrived at the ED of Gaslini Children's Hospital from 10th March 2020 to 30th April 2019 and the same frame of 2020 were performed. We compared two groups by demographics, duration of fever before ED admission, triage code, number of patients hospitalized after ED evaluation. We calculated proportion and incidence rate for airborne infections, fever, and urinary tract infections (UTI), appendicitis, and gastroenteritis for control.Results1362 children arrived at the ED during the lockdown compared to 5628 in the same period of 2019 (−75,8%). No difference was noticed (27.7% vs 28.4%) in the total amount of infectious episodes. A significant reduction in rate of incidence and proportion were observed for upper respiratory tract infections (21,4% vs 28%), otitis (2,6% vs 16,2%), streptococcal infections (0,5% vs 5,2%) and bronchiolitis (2,1% vs 5,7%). Conversely, FUO (27,8 vs 11,1%), infectious mononucleosis (2,6% vs 0,4%), UTI (7,4% vs 2,9%) and appendicitis (6,8% vs 1,1%) significantly increased. Median time from the onset of fever and arrival in ED was significantly lower in 2020 group.ConclusionOur results demonstrated a reduction in community-acquired respiratory infections during the lockdown for COVID-19. The increase in rate of FUO and febrile conditions, together with the short time from fever onset and ED visit could be related to the fear for a SARS-CoV-2 infection.

Community-acquired and hospital-acquired respiratory tract infection and bloodstream infection in patients hospitalized with COVID-19 pneumonia

ObjectivesSARS-CoV-2 may cause acute lung injury, and secondary infections are thus relevant complications in patients with COVID-19 pneumonia. However, detailed information on community- and hospital-acquired infections among patients with COVID-19 pneumonia is scarce.MethodsWe identified 220 SARS-CoV-2-positive patients hospitalized at the University Hospital Basel, Switzerland (between 25 February and 31 May 2020). We excluded patients who declined the general consent (n = 12), patients without clinical evidence of pneumonia (n = 29), and patients hospitalized for < 24 h (n = 17). We evaluated the frequency of community- and hospital-acquired infections using respiratory and blood culture materials with antigen, culture-based, and molecular diagnostics. For ICU patients, all clinical and microbial findings were re-evaluated interdisciplinary (intensive care, infectious disease, and clinical microbiology), and agreement reached to classify patients with infections.ResultsIn the final cohort of 162 hospitalized patients (median age 64.4 years (IQR, 50.4–74.2); 61.1% male), 41 (25.3%) patients were admitted to the intensive care unit, 34/41 (82.9%) required mechanical ventilation, and 17 (10.5%) of all hospitalized patients died. In total, 31 infections were diagnosed including five viral co-infections, 24 bacterial infections, and three fungal infections (ventilator-associated pneumonia, n = 5; tracheobronchitis, n = 13; pneumonia, n = 1; and bloodstream infection, n = 6). Median time to respiratory tract infection was 12.5 days (IQR, 8–18) and time to bloodstream infection 14 days (IQR, 6–30). Hospital-acquired bacterial and fungal infections were more frequent among ICU patients than other patients (36.6% vs. 1.7%). Antibiotic or antifungal treatment was administered in 71 (43.8%) patients.ConclusionsCommunity-acquired viral and bacterial infections were rare among COVID-19 pneumonia patients. By contrast, hospital-acquired bacterial or fungal infections were frequently complicating the course among ICU patients.

СУЧАСНІ МЕТОДИ ЕТІОЛОГІЧНОЇ ДІАГНОСТИКИ ГОСТРИХ НЕГОСПІТАЛЬНИХ ІНФЕКЦІЙ НИЖНІХ ДИХАЛЬНИХ ШЛЯХІВ

MODERN METHODS OF ETIOLOGICAL DIAGNOSING OF ACUTE COMMUNITY-ACQUIRED LOWER RESPIRATORY TRACT INFECTIONS O. L. Bororova, Y. O. Dziublyk, V.A. Iachnyk Abstract The review presents the possibilities presented by various methods of etiological diagnostics used in pulmonology. The main method of diagnosing acute community-aquired lower respiratory tract infections is the microbiological approach which includes microscopy of patient’s material with Gram staining, cultures on nutrient media, isolation of culture, identification and determination of susceptibility of a microorganism to antibiotics. But unfortunately the etiologocal factor cannot be detected in about half of patients. Recently, the popularity of molecular methods of etiological diagnosis has grown. They are characterized by greater sensitivity to microbiological methods and allow to get results faster. Molecular diagnostic tests are divided into four categories depending on the mechanism based on them: immunoassay, hybridization methods, amplification and sequencing methods. Among the tests based on the principles of immunoassay, noteworthy are rapid tests, which are most consistent with the idea of an ideal diagnostic tool in the field of laboratory medicine. They are fast, simple, cheap, highly sensitive and highly specific. However, as the appearance of specific antibodies in the body takes some time, the results of tests based on immunoassay remain positive for several weeks after the delayed episode of acute community-acquired lower respiratory tract infection, so they have diagnostic value only in the presence of clinical manifestations of the disease. The genetic approach allows the detection of infectious agents in the early stages of the disease, when serological and immunological methods are ineffective. Tests based on nucleic acid amplification, including PCR, have also become increasingly common recently. These methods should be used for the diagnosis of atypical pathogens and respiratory viruses, because their cultivation in culture is difficult. Sequencing and mass spectrometry methods are being actively developed, but there are limitations that prevent their use in everyday clinical practice. So the combination of microbiological approach with molecular diagnostic methods is the most optimal for the identification of the causative agent of acute community-acquired lower respiratory tract infections and the use of targeted etiotropic treatment. Key words: acute community-acquired lower respiratory tract infections, etiological diagnosis, microbiological, serological, immunological, molecular genetic methods, ICA, PCR, sequencing, mass spectrometry. Ukr. Pulmonol. J. 2021;29(3):58–65

Левофлоксацин в лечении внебольничных инфекций нижних дыхательных путей: взгляд через четверть века

This review is devoted to the 25th anniversary of the beginning of the widespread use of the prototype of “respiratory” fluoroquinolones levofloxacin in clinical practice. The article presents the evidence of clinical and microbiological efficacy, as well as good tolerability of levofloxacin obtained during numerous clinical studies, as well as evidence of long-term successful use of the antibiotic in real clinical practice, which determines its unique place in modern schemes of antibacterial therapy of adult patients with community-acquired lower respiratory tract infections.

1463. Activity of Delafloxacin against Multi-Drug-Resistant Fastidious Respiratory Pathogens from European Medical Centers (2014-2019)

BackgroundDelafloxacin (DLX) is an anionic fluoroquinolone (FQ) that has been approved in the United States and in Europe for the treatment of acute bacterial skin and skin structure infections and was recently approved in the US for treatment of community-acquired bacterial pneumonia (CABP). In the present study, in vitro susceptibility (S) results for DLX and comparator agents were determined for CABP pathogens including Streptococcus pneumoniae (SPN), Haemophilus influenzae (HI), H. parainfluenzae (HP) and Moraxella catarrhalis (MC) clinical isolates from European hospitals participating in the SENTRY Program during 2014-2019.MethodsA total of 2,835 SPN, 1,484 HI, 959 MC, and 20 HP isolates were collected from community-acquired respiratory tract infections (CARTI) during 2014-2019 from European hospitals. Sites included only 1 isolate/patient/infection episode. Isolate identifications were confirmed at JMI Laboratories. Susceptibility testing was performed according to CLSI broth microdilution methodology, and EUCAST (2020) breakpoints were applied where applicable. Other antimicrobials tested included levofloxacin (LEV) and moxifloxacin (MOX; not tested in 2015). Multidrug-resistant (MDR) SPN isolates were categorized as being nonsusceptible (NS) to amoxicillin-clavulanate, erythromycin (ERY), and tetracycline; other SPN phenotypes were ERY-NS, or penicillin (PEN)-NS. β-lactamase (BL) presence was determined for HI, HP, and MC.ResultsThe activities of the 3 FQs are shown in the table. The most active agent against SPN was DLX, with the lowest MIC50/90 values of 0.015/0.03 mg/L. DLX activities were the same when tested against the MDR or PEN-NS for SPN phenotypes. ERY-NS isolates had DLX MIC50/90 results of 0.015/0.03 mg/L. DLX was the most active FQ against HI, HP, and MC. BL presence did not affect FQ MIC values for HI or MC; only 1 HP isolate was BL-positive.ConclusionDLX demonstrated potent in vitro antibacterial activity against SPN, HI, HP, and MC. DLX was active against MDR SPN that were NS to the agents commonly used as treatments for CABP. These data support the utility of DLX in CABP including when caused by antibiotic resistant strains.Table 1 DisclosuresJennifer M. Streit, BS, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support) Robert K. Flamm, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)