Community-acquired Respiratory Infections Research Articles

Utility of the respiratory viral panel as an antimicrobial stewardship tool.

The development of rapid diagnostics has revolutionized antimicrobial stewardship with efforts targeting earlier de-escalation or discontinuation of antibiotics. The respiratory viral panel (RVP) is one tool quickly able to detect common viral and bacterial pathogens using polymerase chain reaction technology. Utility may be further enhanced in conjunction with procalcitonin (PCT). However, the optimal use of the RVP to the clinical pharmacist in the treatment of community-acquired respiratory infections remains unclear. The purpose of this guide is to review the available literature regarding the impact of the RVP with and without procalcitonin on antimicrobial stewardship efforts and to provide guidance on how to use each of these tools. In total, 13 studies were included, 5 of which utilized PCT in conjunction with RVP and 8 of which did not use PCT. The majority of studies were retrospective in nature, and the most common outcomes evaluated were antibiotic days of therapy (DOT) and time to antibiotic discontinuation. After review, RVP alone has limited value to antimicrobial stewardship; however, when used in conjunction with procalcitonin, RVP has the potential to reduce antibiotic use and duration.

Characteristics and outcomes among patients with community‐acquired respiratory virus infections during the first year after lung transplantation

The current study describes the spectrum of community-acquired respiratory infections (CARV) during the first year after lung transplantation (LT). Additionally, we elucidate variables associated with CARV, management strategies utilized, and impact on early and late outcomes. This was a retrospective study among patients transplanted between 2012 and 2015 (n=255, mean age 55.6±13.5years, M: F 152:103). The diagnosis of CARV was based on the multiplex PCR on nasopharyngeal swab samples. Baseline characteristics, post-transplant variables, and outcomes were compared among patients with and without CARV. Eighty CARV infections developed among a quarter of the study group (n=62, 24.3%). Rhinovirus/enterovirus was the most commonly isolated CARV (n=24) followed by coronavirus (n=17) and RSV (n=9). A significant proportion of episodes (43.8%) required hospitalization. The use of nasal corticosteroids and left single LT was independently associated with an increased risk of CARV. CARV infections did not impact the lung functions during the first year or the CLAD-free survival at 3years. There is a significant burden of CARV infections during the first year after LT. The use of nasal corticosteroids may increase the risk of CARV infection. CARV infections did not impact outcomes.

Febrile Seizures and Respiratory Viruses Determined by Multiplex Polymerase Chain Reaction Test and Clinical Diagnosis.

Febrile seizure (FS) is a common benign seizure disorder of young children. Although upper respiratory tract infection is the cause of fever in most episodes of FS, studies to identify respiratory viruses using a multiplex polymerase chain reaction (mPCR) test have rarely been performed for children with FS. Medical records of children presenting with FS between January 2015 and December 2019 were retrospectively reviewed. Respiratory viruses identified by a rapid influenza detection test and mPCR test were investigated, and their seasonal distribution and the association between viral identification and seizure characteristics were determined. A total of 607 episodes of FS were analyzed: 81.1% of cases were generalized tonic–clonic seizures, 81.5% occurred within 24 h after fever onset, and 87.3% continued for ≤5 min. Complex FS occurred in 17.5% of FS episodes, and epilepsy was diagnosed in 2.5% of tracked cases. Of the 138 mPCR tests performed in 235 hospitalized episodes of FS, 112 (81.2%) tested positive for respiratory viruses: rhinovirus, enterovirus, adenovirus, and influenza virus were most frequently identified. The identified respiratory viruses showed similar seasonal distributions as were observed in community-acquired respiratory tract infections. The identification of a specific respiratory virus was not significantly associated with seizure characteristics or the development of complex FS. In conclusion, respiratory viruses, showing similar seasonal distributions with community-acquired respiratory tract infections and no significant association with the severity and outcomes of FS, should not be rigorously tested for in children with FS.

COVID-19 in lung transplant recipients: A multicenter study.

This study describes the clinical presentation, treatment, and outcomes of SARS-CoV-2 infection in lung transplant recipients (LTRs). This is a multicenter, retrospective study of all adult LTRs with confirmed SARS-CoV-2 infection from March 4 until April 28, 2020 in six Spanish reference hospitals for lung transplantation. Clinical and radiological data, treatment characteristics, and outcomes were reviewed. Forty-four cases were identified in that period. The median time from transplantation was 4.2 (interquartile range: 1.11-7.3) years. Chest radiography showed acute parenchymal abnormalities in 32 (73%) cases. Hydroxychloroquine was prescribed in 41 (93%), lopinavir/ritonavir (LPV/r) in 14 (32%), and tocilizumab in 19 (43%) patients. There was a strong interaction between tacrolimus and LPV/r in all cases. Thirty-seven (84%) patients required some degree of respiratory support and/or oxygen therapy, and 13 (30%) were admitted to intermediate or intensive critical care units. Seventeen (39%) patients had died and 20 (45%) had been discharged at the time of the last follow-up. Deceased patients had a worse respiratory status and chest X-ray on admission and presented with higher D-dimer, interleukin-6, and lactate dehydrogenase levels. In this multicenter LTR cohort, SARS-CoV-2 presented with high mortality. Additionally, the severity of disease on presentation predicted subsequent mortality.

Etiologic Features of Respiratory Tract Infections Seen in Children with Primary Nephrotic Syndrome: A Cross-Sectional Retrospective Study

Background: Respiratory tract infections (RTI) are common complications of primary nephrotic syndrome (PNS) and influence the outcomes of PNS. The pathogenic spectrum and their susceptibility to antibiotics in RTI change over time, which increases the difficulty of treatment. Objectives: To improve the curative effect of RTI in children with PNS, we conducted a cross-sectional retrospective study in 2740 children with PNS to study the etiologic features of RTI seen in PNS children. Methods: Totally 2740 children with PNS hospitalized during 2010 - 2014 were enrolled in this study. Respiratory specimens were collected for the detection of pathogens using current laboratory diagnostic tests. The cases were divided into community-acquired respiratory tract infection (CARTI) and hospital-acquired respiratory tract infection (HARTI) as well as upper respiratory tract infection (URTI) and lower respiratory tract infection (LRTI) to analyse the etiologic features. Results: Among 2162 cases of PNS with RTI, 2095 cases were CARTI (96.90%), and 67 cases were HARTI (3.10%). The most common pathogen in CARTI was Coxsackie virus, followed by Mycoplasma pneumoniae, respiratory syncytial virus, and Streptococcus pneumoniae, while the most common pathogen in HARTI also was Coxsackie virus, followed by respiratory syncytial virus, Mycoplasma pneumoniae, and Streptococcus pneumoniae. There was significant difference in the positive rates of Pseudomonas aeruginosa and Candida albicans between CARTI and HARTI. The distribution of pathogens differed between URTI and LRTI in children with PNS. The positive rates of most pathogens were lower in URTI than LRTI. Generally, the isolation rate of extended-spectrum β-lactamase (ESBL) producing bacteria was relatively low. In CARTI, the sensitive rates of Gram-negative ESBL producing bacteria to carbapenems, amoxicillin/clavulanate potassium, ampicillin/sulbactam, and ciprofloxacin were more than 90.00%, while Gram-positive ESBL producing bacteria were sensitive to glycopeptides, linezolid, macrodantin, mupirocin-HL, and amoxicillin/clavulanate potassium. Conclusions: In children with PNS, the etiology differed between CARTI and HARTI as well as URTI and LRTI. Therefore, it is necessary to differentiate these features for empirical therapy. If the pathogen is bacterial, amoxicillin/clavulanate potassium could be the first choice before sputum culture results are available.

Effects of 13-valent pneumococcal conjugate vaccination of adults on lower respiratory tract infections and antibiotic use in primary care: secondary analysis of a double-blind randomized placebo-controlled study

ObjectivesThe efficacy of 13-valent pneumococcal conjugate vaccine (PCV13) in adults to prevent community-acquired pneumonia (CAP) and lower respiratory tract infections (LRTI) not requiring hospitalization is unknown. We determined the effect of PCV13 on CAP, LRTI and antibiotic use in the primary care setting. MethodsCommunity-dwelling immunocompetent adults over 65 years of age were randomized to PCV13 or placebo as part of the double-blind Community-Acquired Pneumonia immunization Trial in Adults (CAPiTA). CAP and LRTI episodes and antibiotic prescription data were extracted from general practitioner information systems of 40 426 individuals. Vaccine efficacy (VE) of PCV13 was determined using Poisson regression with robust standard errors, comparing CAP and non-CAP LRTI episodes, LRTI-specific and total antibiotic prescriptions. ResultsIn all, 20 195 participants received PCV13 and 20 231 received placebo. A total of 1564 and 1659 CAP episodes occurred in the PCV13 and placebo group, respectively; VE 5.5% (95% CI –2.6% to 13.0%). Non-CAP LRTI episodes occurred 7535 and 7817 times in the PCV13 and placebo groups, respectively; VE 3.4% (95% CI –2.0% to 8.5%). A total of 8835 and 9245 LRTI-related antibiotic courses were prescribed in the PCV13 and placebo arms, respectively; VE 4.2% (95% CI –1.0% to 9.1%). Antibiotic courses for any indication were prescribed 43 386 and 43 309 times, respectively; VE –0.4% (–4.9% to 3.9%). ConclusionsPCV13 vaccination in the elderly is unlikely to cause a relevant reduction in the incidence of CAP, LRTI, LRTI-related antibiotic use or total antibiotic use in primary care.

Rapid Diagnosis of Respiratory Tract Infections Using a Point-of-Care Platform Incorporating a Clinical Decision Support Algorithm.

Respiratory Tract Infections (RTIs) are among the top reasons for visiting a General Practitioner (GP) and the main cause of unnecessary antibiotic prescriptions. Reducing inappropriate use is essential to decrease antibiotic resistance and adverse events. The goal of the Eurostars project "Respiotic" is to develop a new point-of-care (POC) platform based on the centrifugal microfluidic LabDisk that will detect the main responsible viruses and bacteria for community-acquired RTIs, including associated resistances and host biomarkers. The diagnostic platform will use a Polymerase Chain Reaction (PCR) and an immunoassay cartridge on the same instrument and provide the combined analysis within less than 1 h. An electronic clinical algorithm will co-assess the test results and act as a decision support tool for the GPs' patient management and prescriptions.

ALL-045: Community-Acquired Viral Infections in Hospitalized Egyptian Children with Malignancy

Context Children with cancer comprise an important immunocompromised population who are more vulnerable and at high-risk to a variety of infectious pathogens, including respiratory viruses that are widespread in the community. Objective Studying the role of these viruses is important especially in countries with high population density, increasing chances of community-acquired infections. This prospective study aimed to assess the annual prevalence of community-acquired respiratory viral infections among children with cancer presenting with clinical picture suggestive of lower respiratory tract infections (LRTIs), and evaluate its risk factors and prognosis. Design Patients who presented either to the out-patient clinic or to the emergency department, had clinical evidence and/or radiological criteria suggestive of LRTIs, and were fulfilling the criteria of community-acquired infection were recruited, subjected to clinical assessment, investigated through hematology panel, blood culture, chest X-ray, CT chest, and PCR for influenza A and B, parainfluenza (PIV) types 1 and 3 viruses, and respiratory syncytial virus (RSV), and prospectively followed up for the clinical outcome. Results Over a year, 90 eligible children were recruited; 48 patients had ALL, 9 had AML, and 33 had solid tumors; 54.4% of them were in the induction phase. Annual prevalence of viral infections was 37.7%, with a seasonal peak from April to May. The most frequently detected virus was influenza virus [type A (47%), type B (12%)] followed by parainfluenza virus [PIV1 (26%), PIV3 (15%)], and none had RSV. Bacteria were identified in 26 patients, fungi in four, mixed infections (bacterial/viral and bacterial/fungal) in 13, and 36 cases had unidentified etiology. The majority of patients with influenza and parainfluenza infections had haematological malignancy, presented with fever, and had mild self-limited respiratory illness. Five patients with mixed viral and bacterial infection had severe symptoms, necessitating ICU admission. Six patients died from infection-related sequelae; two had mixed PIV and staphylococcal infections. Conclusions Community-acquired influenza and parainfluenza infections are common in pediatrics children with malignancy, either as isolated or mixed viral/bacterial infections. Clinical suspicion is essential as radiological manifestations are non-specific and mandate rapid diagnosis and management to improve patients' outcome.

Epidemiology and persistence of rhinovirus in pediatric lung transplantation.

Infection with rhinovirus (HRV) occurs following pediatric lung transplantation. Prospective studies documenting frequencies, persistence, and progression of HRV in this at-risk population are lacking. In the Clinical Trials in Organ Transplant in Children prospective observational study, we followed 61 lung transplant recipients for 2years. We quantified molecular subtypes of HRV in serially collected nasopharyngeal (NP) and bronchoalveolar lavage (BAL) samples and correlated them with clinical characteristics. We identified 135 community-acquired respiratory infections (CARV) from 397 BAL and 480 NP samples. We detected 93 HRV events in 42 (68.8%) patients, 22 of which (23.4%) were symptomatic. HRV events were contiguous with different genotypes identified in 23 cases, but symptoms were not preferentially associated with any particular species. Nine (9.7%) HRV events persisted over multiple successive samples for a median of 36days (range 18-408days). Three persistent HRV were symptomatic. When we serially measured forced expiratory volume in one second (FEV1) in 23 subjects with events, we did not observe significant decreases in lung function over 12months post-HRV. In conjunction with our previous reports, our prospectively collected data indicate that molecularly heterogeneous HRV infections occur commonly following pediatric lung transplantation, but these infections do not negatively impact clinical outcomes.

Community-acquired viral respiratory infections amongst hospitalized inpatients during a COVID-19 outbreak in Singapore: co-infection and clinical outcomes.

During the ongoing COVID-19 outbreak, co-circulation of other common respiratory viruses can potentially result in co-infections; however, reported rates of co-infections for SARS-CoV-2 vary. We sought to evaluate the prevalence and etiology of all community acquired viral respiratory infections requiring hospitalization during an ongoing COVID-19 outbreak, with a focus on co-infection rates and clinical outcomes. Over a 10-week period, all admissions to our institution, the largest tertiary hospital in Singapore, were screened for respiratory symptoms, and COVID-19 as well as a panel of common respiratory viral pathogens were systematically tested for. Information was collated on clinical outcomes, including requirement for mechanical ventilation and in hospital mortality. One-fifth (19.3%, 736/3807) of hospitalized inpatients with respiratory symptoms had a PCR-proven viral respiratory infection; of which 58.5% (431/736) tested positive for SARS-CoV-2 and 42.2% (311/736) tested positive for other common respiratory viruses. The rate of co-infection with SARS-CoV-2 was 1.4% (6/431); all patients with co-infection had mild disease and stayed in communal settings. The in-hospital mortality rate and proportion of COVID-19 patients requiring invasive ventilation was low, at around 1% of patients; these rates were lower than patients with other community-acquired respiratory viruses admitted over the same period (p < 0.01). Even amidst an ongoing COVID-19 outbreak, common respiratory viruses still accounted for a substantial proportion of hospitalizations. Coinfections with SARS-CoV-2 were rare, with no observed increase in morbidity or mortality.

Pharmacokinetics and pharmacodynamics of levofloxacin in bronchial mucosa and lung tissue of patients undergoing pulmonary operation.

Levofloxacin is a major antimicrobial agent that is used for the treatment of community-acquired lower respiratory tract infections (LRTIs). The present study was designed to investigate the pharmacokinetics (PK) and pharmacodynamics (PD) of levofloxacin in bronchial mucosa and lung tissue. A total of 32 patients undergoing pulmonary surgery were randomly assigned to one of four groups (8 subjects/group). All patients received a single dose of 500 mg levofloxacin orally prior to the operation. Blood, lung tissue and bronchial mucosa samples were collected prior to treatment and at 1.5, 4, 8, 12 and 24 h following treatment. The drug concentration was determined and PK and PD profiles were calculated using MATLAB software. The peak concentration of levofloxacin was 7.0±1.2 µg/g in lung tissues and 9.4±2.1 µg/g in bronchial mucosa. The corresponding area under the curve between 0 and 24 h (AUC0-24) was 85.7±8.5 and 137.3±19.4 µg h/g. The mean permeability of levofloxacin (ratio of concentration in tissue to that in plasma) was 2.4 in lung tissue and 4.4 in the bronchial mucosa. The PK profiles of levofloxacin in the plasma, lung and bronchial mucosa were described using an integrated one-compartment model. The probability of fAUC0-24/minimal inhibitory concentration (MIC) target attainment of levofloxacin against Streptococcus pneumoniae in the lung and bronchial mucosa was maintained at 100% when MIC ≤1 mg/l, while the cumulative fraction of fAUC0-24/MIC in the corresponding tissues was 94.4 and 98.1%, respectively. The present study demonstrated the high permeability of levofloxacin in the lung and bronchial mucosa of patients undergoing pulmonary surgery. In conclusion, treatment using 500 mg levofloxacin exhibits good clinical and microbiological efficacy for use in LRTIs that are caused by S. pneumoniae. This trial was registered retrospectively in the Chinese Clinical Trial Registry on January 13, 2020 (registration no. ChiCTR2000029096).

In Vitro and Intracellular Activities of Omadacycline against Legionella pneumophila.

Omadacycline is an aminomethylcycline antibiotic with in vitro activity against pathogens causing community-acquired bacterial pneumonia (CABP). This study investigated the activity of omadacycline against Legionella pneumophila strains isolated between 1995 and 2014 from nosocomial or community-acquired respiratory infections. Omadacycline exhibited extracellular activity similar to comparator antibiotics; intracellular penetrance was found by day 3 of omadacycline exposure. These results support the utility of omadacycline as an effective antibiotic for the treatment of CABP caused by L. pneumophila.

Results from the Survey of Antibiotic Resistance (SOAR) 2016-18 in Vietnam, Cambodia, Singapore and the Philippines: data based on CLSI, EUCAST (dose-specific) and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints.

To determine antibiotic susceptibility of Streptococcus pneumoniae and Haemophilus influenzae isolates collected from community-acquired respiratory tract infections (CA-RTIs) in 2016-18 in four Asian countries. MICs were determined by CLSI broth microdilution and susceptibility was assessed using CLSI, EUCAST (dose-specific) and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. In total, 260 S. pneumoniae and 258 H. influenzae isolates were tested. Pneumococci from Vietnam (n = 161) were the least susceptible, with rates of susceptibility >90% for fluoroquinolones by CLSI breakpoints, ∼60% for amoxicillin, amoxicillin/clavulanic acid and ceftriaxone but <14% for most other agents. Pneumococcal isolates from Cambodia (n = 48) and Singapore (n = 34) showed susceptibilities ranging from ∼30% for trimethoprim/sulfamethoxazole and oral penicillin to 100% for fluoroquinolones. Among isolates of H. influenzae from Cambodia (n = 30), the Philippines (n = 59) and Singapore (n = 80), rates of susceptibility using CLSI breakpoints were >90% for amoxicillin/clavulanic acid, cephalosporins [except cefaclor in Singapore (77.5%)], macrolides and fluoroquinolones; for isolates from Vietnam (n = 89) the rates of susceptibility were >85% only for amoxicillin/clavulanic acid (95.5%), ceftriaxone (100%) and macrolides (87.6%-89.9%). Susceptibility to other antibiotics ranged from 7.9% (trimethoprim/sulfamethoxazole) to 57.3%-59.6% (fluoroquinolones) and 70.8% (cefixime). The application of different EUCAST breakpoints for low and higher doses for some of the antibiotics (amoxicillin, amoxicillin/clavulanic acid, ampicillin, penicillin, ceftriaxone, clarithromycin, erythromycin, levofloxacin and trimethoprim/sulfamethoxazole) allowed, for the first time in a SOAR study, the effect of raising the dosage on susceptibility to be quantified. A limitation of the study was the small sample sizes and only one or two sites participating per country; however, since susceptibility data are scarce in some of the participating countries any information concerning antibiotic susceptibility is of value. Antibiotic susceptibility varied across countries and species, with isolates from Vietnam demonstrating the lowest susceptibility. Knowledge of resistance patterns can be helpful for clinicians when choosing empirical therapy options for CA-RTIs.

Results from the Survey of Antibiotic Resistance (SOAR) 2015–17 in Latin America (Argentina, Chile and Costa Rica): data based on CLSI, EUCAST (dose-specific) and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints

To determine antibiotic susceptibility of Streptococcus pneumoniae and Haemophilus influenzae isolates from community-acquired respiratory tract infections (CA-RTIs) collected in 2015-17 from Argentina, Chile and Costa Rica. MICs were determined by CLSI broth microdilution and susceptibility was assessed using CLSI, EUCAST (dose-specific) and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. A total of 170 S. pneumoniae and 218 H. influenzae isolates were collected at five centres in Argentina, Chile and Costa Rica in 2015-17. Small S. pneumoniae isolate numbers from Costa Rica (n = 2) meant that these could only be included in the penicillin susceptibility analysis; they were excluded from further country analyses. Around one-third of pneumococcal isolates from Argentina and two-thirds from Chile were non-susceptible to penicillin by CLSI oral or EUCAST low-dose IV breakpoints, but most (≥89%) were susceptible by CLSI IV or EUCAST high-dose breakpoints. Amongst pneumococci from Argentina, about 80% or more were susceptible to most other antibiotics except cefaclor (all breakpoints), cefixime (PK/PD breakpoints), cefuroxime (EUCAST breakpoints) and trimethoprim/sulfamethoxazole (CLSI and PK/PD breakpoints). S. pneumoniae isolates from Chile showed significantly lower susceptibility (P < 0.05) using CLSI breakpoints compared with those from Argentina for many of the antibiotics tested. Among isolates of H. influenzae from Latin America, more than 90% were susceptible to amoxicillin/clavulanic acid (high dose), cefixime, cefpodoxime, ceftriaxone and fluoroquinolones, irrespective of the breakpoints used. The application of different EUCAST breakpoints for low and higher doses for some of the antibiotics (amoxicillin, amoxicillin/clavulanic acid, ampicillin, penicillin, ceftriaxone, clarithromycin, erythromycin, levofloxacin and trimethoprim/sulfamethoxazole) allowed, for the first time in a SOAR study, the effect of raising the dosage on susceptibility to be quantified. Antibiotic susceptibility of H. influenzae isolates was generally high in the Latin American countries studied; however, susceptibility profiles varied for S. pneumoniae by country and depending on the breakpoints used, especially for cefaclor. These factors are important in decision making for empirical therapy of bacterial infections.

Results from the Survey of Antibiotic Resistance (SOAR) 2015-17 in the Middle East (Kuwait, Lebanon and Saudi Arabia): data based on CLSI, EUCAST (dose-specific) and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints.

To determine antibiotic susceptibility of Streptococcus pneumoniae and Haemophilus influenzae isolates from community-acquired respiratory tract infections (CA-RTIs) collected in 2015-17 from Kuwait, Lebanon and Saudi Arabia. MICs were determined by CLSI broth microdilution and susceptibility was assessed using CLSI, EUCAST (dose-specific) and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. A total of 139 S. pneumoniae isolates were collected from four centres in Kuwait, Lebanon and Saudi Arabia in 2015-17 and 55 H. influenzae isolates were collected and analysed from Saudi Arabia over the same time period. Pneumococci from all three countries were commonly non-susceptible to penicillin based on CLSI oral or low-dose IV penicillin using EUCAST breakpoints (39% in Kuwait to 57.1% in Lebanon) but by CLSI IV and EUCAST high-dose breakpoints most isolates were susceptible (∼90% in Kuwait and Saudi Arabia, and 100% in Lebanon). Isolates from Lebanon were highly susceptible to most other antibiotics (>90%) except cefaclor, oral cefuroxime and cefpodoxime (EUCAST breakpoints only). Overall, susceptibility was significantly lower in Kuwait and Saudi Arabia than Lebanon. Although all H. influenzae isolates (Saudi Arabia only) were β-lactamase negative, 3.6% and 12.7% were ampicillin resistant by CLSI and EUCAST breakpoints, respectively. Otherwise susceptibility was high in H. influenzae. The application of different EUCAST breakpoints for low and higher doses for some of the antibiotics (amoxicillin, amoxicillin/clavulanic acid, ampicillin, penicillin, ceftriaxone, clarithromycin, erythromycin, levofloxacin and trimethoprim/sulfamethoxazole) allowed, for the first time in a SOAR study, the effect of raising the dosage on susceptibility to be quantified. Relatively low antibiotic susceptibility was observed in S. pneumoniae from Kuwait and Saudi Arabia in contrast to Lebanon, where rates of susceptibility were generally higher. Isolates of H. influenzae from Saudi Arabia were susceptible to most antibiotics. These factors are important in decision making for empirical therapy of CA-RTIs.

Results from the Survey of Antibiotic Resistance (SOAR) 2016-17 in Ukraine: data based on CLSI, EUCAST (dose-specific) and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints.

To determine antibiotic susceptibility of Streptococcus pneumoniae and Haemophilus influenzae isolates from community-acquired respiratory tract infections (CA-RTIs) collected in 2016-17 from Ukraine. MICs were determined by CLSI broth microdilution and susceptibility was assessed using CLSI, EUCAST (dose-specific) and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. A total of 177 viable clinical isolates, including 78 S. pneumoniae and 99 H. influenzae, were collected. Overall, ∼98% of S. pneumoniae isolates were susceptible to penicillin by CLSI IV or EUCAST high-dose breakpoints and 73.1% were susceptible by CLSI oral or EUCAST low-dose IV breakpoints. Susceptibility rates of 76.9%-100% were observed for most antibiotics by all breakpoints except trimethoprim/sulfamethoxazole (41%-69.2%) and cefaclor, which showed the greatest difference between breakpoints: 0% by EUCAST, 28.2% by PK/PD and 73.1% by CLSI. All S. pneumoniae isolates were susceptible to amoxicillin/clavulanic acid by CLSI and PK/PD breakpoints. H. influenzae isolates were almost all β-lactamase negative (90.9%). One isolate was β-lactamase negative and ampicillin resistant (BLNAR) by CLSI and four isolates were BLNAR by EUCAST criteria. Susceptibility of isolates was high (≥90.9%) by CLSI breakpoints for all antibiotics tested except trimethoprim/sulfamethoxazole (61.6%). Susceptibility using EUCAST breakpoints was similar for ampicillin (90.9%) and amoxicillin/clavulanic acid (95%) but was low for cefuroxime (oral), where only 10.1% of isolates were susceptible. All S. pneumoniae and H. influenzae isolates were susceptible to the fluoroquinolones by all breakpoints. Susceptibility to ceftriaxone was also 100% for H. influenzae and ≥91% for S. pneumoniae isolates by all breakpoints. The application of different EUCAST breakpoints for low and higher doses for some of the antibiotics (amoxicillin, amoxicillin/clavulanic acid, ampicillin, penicillin, ceftriaxone, clarithromycin, erythromycin, levofloxacin and trimethoprim/sulfamethoxazole) allowed, for the first time in a SOAR study, the effect of raising the dosage on susceptibility to be quantified. Antibiotic susceptibility in these respiratory tract pathogens was generally high in Ukraine. These data are important for empirical therapy choices in the treatment of CA-RTIs.

Results from the Survey of Antibiotic Resistance (SOAR) 2015-17 in Turkey: data based on CLSI, EUCAST (dose-specific) and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints.

To determine antibiotic susceptibility of Streptococcus pneumoniae and Haemophilus influenzae isolates from community-acquired respiratory tract infections (CA-RTIs) collected in 2015-17 from Turkey. MICs were determined by CLSI broth microdilution and susceptibility was assessed using CLSI, EUCAST (dose-specific) and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. A total of 179 S. pneumoniae and 239 H. influenzae isolates were collected. Few (27.9%) pneumococci were penicillin susceptible by CLSI oral or EUCAST low-dose breakpoints, but by EUCAST high-dose or CLSI IV breakpoints 84.4% were susceptible. The most active antibiotics (excluding penicillin IV) by CLSI breakpoints were fluoroquinolones (98.9% of isolates susceptible), ceftriaxone (83.2%), amoxicillin (78.8%) and amoxicillin/clavulanic acid (78.8%). Pneumococcal susceptibility to amoxicillin and amoxicillin/clavulanic acid was lower using EUCAST low-dose breakpoints (49.7%), although susceptibility increased when using EUCAST high-dose (57.0%-58.1%) and PK/PD (78.8%-87.7%) breakpoints. Twenty-three H. influenzae isolates were β-lactamase positive, with 11 characterized as β-lactamase negative and ampicillin resistant following EUCAST criteria and 5 by CLSI criteria. Generally antibiotic susceptibility was high using CLSI breakpoints: ≥92.9% for all antibiotics except ampicillin (87% by CLSI and EUCAST breakpoints) and trimethoprim/sulfamethoxazole (67.4% and 72% by CLSI and EUCAST breakpoints, respectively). Susceptibility using EUCAST breakpoints (where these are published) was similar, except for cefuroxime (oral) with 3.8% of isolates susceptible. PK/PD breakpoints indicated low susceptibility to macrolides (5.9%-10%) and cefaclor (13%). The application of different EUCAST breakpoints for low and higher doses for some of the antibiotics (amoxicillin, amoxicillin/clavulanic acid, ampicillin, penicillin, ceftriaxone, clarithromycin, erythromycin, levofloxacin and trimethoprim/sulfamethoxazole) allowed, for the first time in a SOAR study, the effect of raising the dosage on susceptibility to be quantified. Antibiotic susceptibility of S. pneumoniae was generally low, which is in keeping with evidence of inappropriate and high antibiotic use in Turkey. H. influenzae susceptibility was high. These data are important for empirical therapy of CA-RTIs.

Results from the Survey of Antibiotic Resistance (SOAR) 2015-17 in Pakistan: data based on CLSI, EUCAST (dose-specific) and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints.

To determine antibiotic susceptibility of community-acquired respiratory tract infection (CA-RTI) isolates of Streptococcus pneumoniae and Haemophilus influenzae collected in 2015-17 from Pakistan. MICs were determined by CLSI broth microdilution and susceptibility was assessed using CLSI, EUCAST (dose-specific) and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. A total of 94 S. pneumoniae and 122 H. influenzae isolates were collected. Susceptibility to penicillin was noted in 23.4% of the S. pneumoniae isolates by CLSI oral/EUCAST low-dose IV breakpoints, although by CLSI IV and EUCAST high-dose breakpoints all isolates were characterized as susceptible. Susceptibility to trimethoprim/sulfamethoxazole (10.6%), macrolides (33%) and cefaclor (28.7%) was low but higher susceptibility was observed to ceftriaxone (100%), amoxicillin and amoxicillin/clavulanic acid (98.9%), cefuroxime (oral, 97.9%), cefpodoxime (96.8%), fluoroquinolones (93.6%-96.8%) and cefdinir (76.6%) by CLSI breakpoints. However, using EUCAST breakpoints, susceptibility to cefpodoxime (70.2%) and cefuroxime (oral, 61.7%) was reduced. H. influenzae isolates were almost all β-lactamase negative (96.7%). Using CLSI breakpoints, ≥93.4% of isolates were susceptible to all antibiotics tested except fluoroquinolones (75.4%-77.1%) and trimethoprim/sulfamethoxazole (41%). The proportion of isolates susceptible using EUCAST breakpoints was similar or identical for penicillins, trimethoprim/sulfamethoxazole and the cephalosporins that have EUCAST breakpoints; the proportion of isolates susceptible using EUCAST breakpoints was similar or identical to that using CSLI breakpoints except for cefuroxime (oral), where only 1.6% of isolates were considered susceptible. Susceptibility of H. influenzae to fluoroquinolones was also lower by EUCAST breakpoints (33.6%-34.4%). The application of different EUCAST breakpoints for low and higher doses for some of the antibiotics (amoxicillin, amoxicillin/clavulanic acid, ampicillin, penicillin, ceftriaxone, clarithromycin, erythromycin, levofloxacin and trimethoprim/sulfamethoxazole) allowed, for the first time in a SOAR study, the effect of raising the dosage on susceptibility to be quantified. Antibiotic susceptibility in these important respiratory tract pathogens varied in Pakistan based on different breakpoints. These data are important for empirical therapy choices in the treatment of CA-RTIs.

Results from the Survey of Antibiotic Resistance (SOAR) 2015-18 in Tunisia, Kenya and Morocco: data based on CLSI, EUCAST (dose-specific) and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints.

To determine antibiotic susceptibility of community-acquired respiratory tract infection (CA-RTI) isolates of Streptococcus pneumoniae and Haemophilus influenzae collected in 2015-18 from Tunisia, Kenya and Morocco. MICs were determined by CLSI broth microdilution and susceptibility was assessed using CLSI, EUCAST (dose-specific) and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. S. pneumoniae isolates from Tunisia (n = 79), Kenya (n = 44) and Morocco (n = 19) and H. influenzae isolates (n = 74) from Tunisia only were collected and analysed. Low antibiotic susceptibility was observed in S. pneumoniae from Tunisia, with >90% susceptible only to the fluoroquinolones (all breakpoints), penicillin (CLSI IV and EUCAST high-dose) and ceftriaxone (CLSI, EUCAST high-dose and PK/PD breakpoints). In addition, isolate susceptibility in Kenya was >90% to amoxicillin and amoxicillin/clavulanic acid (CLSI and PK/PD breakpoints). Antibiotic activity was highest in Morocco, where ≥89.5% of pneumococci were susceptible to most antibiotics, excluding trimethoprim/sulfamethoxazole (68.4% by CLSI or PK/PD and 79%-84.2% by EUCAST), macrolides (79%-84.2% by all breakpoints) and cefaclor (0% by EUCAST and 52.6% by PK/PD). The majority (≥86.5%) of H. influenzae isolates from Tunisia were susceptible to most antibiotics by all available breakpoints, except ampicillin and amoxicillin (almost one-third were β-lactamase positive), trimethoprim/sulfamethoxazole (51.4%-56.8%), cefaclor (1.4% by PK/PD), cefuroxime (4.1% by EUCAST), macrolides (1.4%-2.7% by PK/PD) and cefdinir (66.2% by PK/PD). The application of different EUCAST breakpoints for low and higher doses for some of the antibiotics (amoxicillin, amoxicillin/clavulanic acid, ampicillin, penicillin, ceftriaxone, clarithromycin, erythromycin, levofloxacin and trimethoprim/sulfamethoxazole) allowed, for the first time in a SOAR study, the effect of raising the dosage on susceptibility to be quantified. Low antibiotic susceptibility was observed in S. pneumoniae from Tunisia, but susceptibility was higher in isolates from Kenya and highest in those from Morocco. H. influenzae from Tunisia were highly susceptible to most antibiotics. These factors are important in decision making for empirical therapy of CA-RTIs.

Diagnostic Utility of Serology and Polymerase Chain Reaction for Detection of Mycoplasma pneumoniae and Chlamydophila pneumoniae in Paediatric Community-acquired Lower Respiratory Tract Infections

AbstractPurpose:Mycoplasma pneumoniae (M. pneumoniae) and Chlamydophila pneumoniae (C. pneumoniae) play a significant role in children of all ages with lower respiratory tract infections (LRTIs). This study was conducted to detect M. pneumoniae and C. pneumoniae in children with community-acquired LRTIs employing serology, polymerase chain reaction (PCR) and nested PCR analysis. Material and Methods: This study included 75 children with acute LRTIs for detection of M. pneumoniae and C. pneumoniae. Blood was obtained for M. pneumoniae and C. pneumoniae antibodies and nasopharyngeal aspirates for M. pneumoniae PCR and C. pneumoniae nested PCR. Results:M. pneumoniae infection was positive in 9 (64.21%) children aged 2–6 months and in 5 (35.79%) aged 7 months–12 years, and this difference was statistically significant (P = 0.002). C. pneumoniae infection was comparable within the age group and statistically insignificant (P = 0.43). Clinical and radiological profiles of M. pneumoniae- and C. pneumoniae-positive and negative patients were numerically comparable. Serology and PCR together detected M. pneumoniae infection in 14 (18.6%) children. The sensitivity, specificity and positive and negative predictive values of serology were 77.78%, 92.42%, 58.33% and 96.83%, respectively. C. pneumoniae infection was positive in 11 (14.6%) children by serology and nested PCR with 50% sensitivity, 87.67% specificity, 10% positive predictive value and 98.46% negative predictive value. Conclusions: Our study confirms that M. pneumoniae and C. pneumoniae play a significant role in community-acquired LRTIs and a combination of serology and nested PCR is useful for its diagnosis.