Underascertainment of Respiratory Syncytial Virus Infection in Adults Due to Diagnostic Testing Limitations: A Systematic Literature Review and Meta-analysis.

BACKGROUND: Most observational population-based studies identify respiratory syncytial virus (RSV) by nasal/nasopharyngeal swab reverse transcriptase real-time PCR (RT-PCR) only. We conducted a systematic review and meta-analyses to quantify specimen and diagnostic testing-based underascertainment of adult RSV infection. METHODS: EMBASE, PubMed, and Web of Science were searched (January 2000-December 2021) for studies including adults using/comparing >1 RSV testing approach. We quantified test performance and RSV detection increase associated with using multiple specimen types. RESULTS: Among 8066 references identified, 154 met inclusion. Compared to RT-PCR, other methods were less sensitive: rapid antigen detection test (RADT; pooled sensitivity, 64%), direct fluorescent antibody (DFA; 83%), and viral culture (86%). Compared to singleplex PCR, multiplex PCR's sensitivity was lower (93%). Compared to nasal/nasopharyngeal swab RT-PCR alone, adding another specimen type increased detection: sputum RT-PCR, 52%; 4-fold rise in paired serology, 44%; and oropharyngeal swab RT-PCR, 28%. Sensitivity was lower in estimates limited to only adults (for RADT, DFA, and viral culture), and detection rate increases were largely comparable. CONCLUSIONS: RT-PCR, particularly singleplex testing, is the most sensitive RSV diagnostic test in adults. Adding additional specimen types to nasopharyngeal swab RT-PCR testing increased RSV detection. Synergistic effects of using ≥3 specimen types should be assessed, as this approach may improve the accuracy of adult RSV burden estimates.

Respiratory syncytial virus (RSV) is an important cause of illness and death among older adults. Most studies of how frequent RSV infection is among older adults use only nasal swab testing to identify RSV infection. These nasal swabs are checked for genetic material from the virus, known as polymerase chain reaction (PCR) testing. We examined published studies from January 2000 to December 2021 to estimate how many RSV infections would be missed by using only this approach to RSV testing. We found 154 studies had information to answer our question. Compared to PCR testing of nasal swab alone, adding sputum specimen PCR testing (ie, testing cough mucus or phlegm for RSV genetic material) increased RSV infections found by 52%. Adding blood testing increased RSV infections found by 44%. Adding mouth/throat swab PCR testing, increased RSV infections by 28%. In summary, adding additional specimen types to nasal swab PCR testing increased RSV detection. Impact of using 3 or more specimen types at the same time should be assessed, as this approach may further improve accuracy.

Pediatric Respiratory Syncytial Virus Diagnostic Testing Performance: A Systematic Review and Meta-analysis.

BACKGROUND: Adding additional specimen types (eg, serology or sputum) to nasopharyngeal swab (NPS) reverse transcription polymerase chain reaction (RT-PCR) increases respiratory syncytial virus (RSV) detection among adults. We assessed if a similar increase occurs in children and quantified underascertainment associated with diagnostic testing. METHODS: We searched databases for studies involving RSV detection in persons <18 years using ≥2 specimen types or tests. We assessed study quality using a validated checklist. We pooled detection rates by specimen and diagnostic tests and quantified performance. RESULTS: We included 157 studies. Added testing of additional specimens to NP aspirate (NPA), NPS, and/or nasal swab (NS) RT-PCR resulted in statistically nonsignificant increases in RSV detection. Adding paired serology testing increased RSV detection by 10%, NS by 8%, oropharyngeal swabs by 5%, and NPS by 1%. Compared to RT-PCR, direct fluorescence antibody tests, viral culture, and rapid antigen tests were 87%, 76%, and 74% sensitive, respectively (pooled specificities all ≥98%). Pooled sensitivity of multiplex versus singleplex RT-PCR was 96%. CONCLUSIONS: RT-PCR was the most sensitive pediatric RSV diagnostic test. Adding multiple specimens did not substantially increase RSV detection, but even small proportional increases could result in meaningful changes in burden estimates. The synergistic effect of adding multiple specimens should be evaluated.

Incidence and diagnosis of ventilator-associated tracheobronchitis in the intensive care unit: an international online survey.

INTRODUCTION: Several aspects of ventilator-associated tracheobronchitis (VAT)-including diagnostic criteria, overlap with ventilator-associated pneumonia (VAP), and appropriate treatment regimens-remain poorly defined. The objectives of this study were to survey reported practices in the clinical and microbiological diagnosis of VAT and to evaluate perceptions of the impact of VAT on patient outcomes. METHODS: We developed a questionnaire consisting of (a) characteristics of the respondent, the ICU, and hospital; (b) current clinical and microbiological diagnostic approach; (c) empirical antibiotic therapy; and (d) the perception of physicians regarding the clinical impact of VAT and its implications. RESULTS: A total of 288 ICUs from 16 different countries answered the survey: 147 (51%) from the Latin American (LA) group and 141 (49%) from Spain, Portugal, and France (SPF group). The majority of respondents (n = 228; 79.2%) reported making the diagnosis of VAT based on clinical and microbiological criteria, and 40 (13.9%) by clinical criteria alone. Approximately half (50.3%) of the respondents agreed that patients should receive antibiotics for the treatment of VAT. Out of all respondents, 269 (93.4%) assume that a VAT episode increases ICU length of stay, and this perception is greater in the LA group (97.3%) than in the SPF group (89.4%, P <0.05). Half of the physicians considered that VAT increases the risk of mortality, and this perception is again greater in the LA group (58.5% versus 41.1%, P <0.05). CONCLUSIONS: Given the possible high incidence of VAT and the perception of its importance as a risk factor for VAP and mortality, a large multicenter international prospective study would be helpful to validate a consensual definition of VAT, determine its incidence, and delineate its impact on subsequent VAP occurrence.

Respiratory Syncytial Virus Sequelae Among Adults in High-Income Countries: A Systematic Literature Review and Meta-analysis.

INTRODUCTION: Respiratory syncytial virus (RSV) can cause severe respiratory infections in adults; however, information on associated sequelae is limited. This systematic literature review aimed to identify sequelae in adults within 1 year following RSV-related hospitalization or resolution of acute infection. METHODS: Studies were identified from Embase, MEDLINE, LILACS, SciELO, and grey literature. Random-effects meta-analyses using restricted maximum likelihood were used to calculate the proportions and relative risks of sequelae in patients with RSV compared with controls (patients with RSV-negative influenza-like illness, influenza, and parainfluenza) per follow-up period, population, and treatment setting, where possible. RESULTS: Twenty-one relevant studies covering the period from 1990 to 2019 were included. Among the general population, the most frequent clinical sequela was sustained function loss (33.5% [95% CI 27.6-39.9]). Decline in lung function and cardiovascular event or congestive heart failure were also identified. Utilization sequelae were readmission (highest at > 6 months after discharge) and placement in a skilled nursing facility. The only subpopulation with data regarding sequelae was transplant patients. Among lung transplant patients, the most frequently reported clinical sequelae were decline in lung function, followed by graft dysfunction and bronchiolitis obliterans syndrome. Pooled relative risks were calculated for the following sequela with controls (primarily influenza-positive patients): cardiovascular event (general population) and pulmonary impairment (hematogenic-transplant patients) both 1.4 (95% CI 1.0-2.0) and for readmission (general population) 1.2 (95% CI 1.1-1.3). CONCLUSIONS: Although less data are available for RSV than for influenza or other lower respiratory tract infections, RSV infection among adults is associated with medically important sequelae, with a prevalence similar to other respiratory pathogens. RSV sequelae should be included in disease burden estimates.

Rates of Lower Respiratory Tract Illness in US Adults by Age and Comorbidity Profile.

INTRODUCTION: While it is widely recognized that older adults, adults with chronic medical conditions (CMC), and adults with immunocompromising conditions (IC) are at increased risk of lower respiratory tract illness (LRTI), evidence of the magnitude of increased risk is limited. This study was thus undertaken to characterize rates of hospitalized and ambulatory LRTI among United States (US) adults by age and comorbidity profile. METHODS: A retrospective cohort design and US healthcare claims database (2016-2019) were employed. Study population included adults aged ≥ 18 years and was stratified by age and comorbidity profile (CMC-, CMC+ , IC). LRTI was ascertained overall and by pathogen pathogen (e.g., respiratory syncytial virus [RSV]), and was classified by care setting (hospital, emergency department [ED], physician office/hospital outpatient [PO/HO]). RESULTS: Relative rates (RR) of LRTI generally increased with older age across care settings (vs. 18-49 years), with the most marked increase for hospitalizations: for LRTI-hospitalized, RRs ranged from 3.3 for 50-64 years to 46.6 for ≥ 85 years; for LRTI-ED and LRTI-PO/HO, RRs ranged from 1.0 to 2.7 and from 1.3 to 1.5, respectively. Within age groups, LRTI rates were also consistently higher among CMC+ and IC adults (vs. CMC- adults). Age-specific RRs of LRTI patients hospitalized due to RSV were largely comparable to overall LRTI; age-specific RRs for other care settings, and RRs for CMC+ and IC adults (vs. CMC- adults), were generally higher for LRTI due to RSV. CONCLUSIONS: Incidence of LRTI, including that due to RSV, especially for events requiring acute inpatient care, is markedly higher among older adults and adults of all ages with CMC or IC.

Differences Between RSV A and RSV B Subgroups and Implications for Pharmaceutical Preventive Measures.

INTRODUCTION: Understanding the differences between respiratory syncytial virus (RSV) subgroups A and B provides insights for the development of prevention strategies and public health interventions. We aimed to describe the structural differences of RSV subgroups, their epidemiology, and genomic diversity. The associated immune response and differences in clinical severity were also investigated. METHODS: A literature review from PubMed and Google Scholar (1985-2023) was performed and extended using snowballing from references in captured publications. RESULTS: RSV has two major antigenic subgroups, A and B, defined by the G glycoprotein. The RSV F fusion glycoprotein in the prefusion conformation is a major target of virus neutralizing antibodies and differs in surface exposed regions between RSV A and RSV B. The subgroups co-circulate annually, but there is considerable debate as to whether clinical severity is impacted by the subgroup of the infecting RSV strain. Large variations between the studies reporting RSV subgroup impact on clinical severity were observed. A tendency for higher disease severity may be attributed to RSV A but no consensus could be reached as to whether infection by one of the subgroup caused more severe outcomes. RSV genotype diversity decreased over the last two decades, and ON and BA have become the sole lineages detected for RSV A and RSV B, since 2014. No studies with data obtained after 2014 reported a difference in disease severity between the two subgroups. RSV F is relatively well conserved and highly similar between RSV A and B, but changes in the amino acid sequence have been observed. Some of these changes led to differences in F antigenic sites compared to reference F sequences (e.g., RSV/A Long strain), which are more pronounced in antigenic sites of the prefusion conformation of RSV B. Initial results from the second season after vaccination suggest specific RSV B efficacy wanes more rapidly than RSV A for RSV PreF-based monovalent vaccines. CONCLUSIONS: RSV A and RSV B both contribute substantially to the global RSV burden. Both RSV subgroups cause severe disease and none of the available evidence to date suggests any differences in clinical severity between the subgroups. Therefore, it is important to implement measures effective at preventing disease due to both RSV A and RSV B to ensure impactful public health interventions. Monitoring overtime will be needed to assess the impact of waning antibody levels on subgroup-specific efficacy.

Attributable Cost of Adult Respiratory Syncytial Virus Illness Beyond the Acute Phase.

Background: Estimates of the cost of medically attended lower respiratory tract illness (LRTI) due to respiratory syncytial virus (RSV) in adults, especially beyond the acute phase, is limited. This study was undertaken to estimate the attributable costs of RSV-LRTI among US adults during, and up to 1 year after, the acute phase of illness. Methods: A retrospective observational matched-cohort design and a US healthcare claims repository (2016-2019) were employed. The study population comprised adults aged ≥18 years with RSV-LRTI requiring hospitalization (RSV-H), an emergency department visit (RSV-ED), or physician office/hospital outpatient visit (RSV-PO/HO), as well as matched comparison patients. All-cause healthcare expenditures were tallied during the acute phase of illness (RSV-H: from admission through 30 days postdischarge; ambulatory RSV: during the episode) and long-term phase (end of acute phase to end of following 1-year period). Results: The study population included 4526 matched pairs of RSV-LRTI and comparison patients (RSV-H: n = 970; RSV-ED: n = 590; RSV-PO/HO: n = 2966). Mean acute-phase expenditures were $42 179 for RSV-H (vs $5154 for comparison patients), $4409 for RSV-ED (vs $377), and $922 for RSV-PO/HO (vs $201). By the end of the 1-year follow-up period, mean expenditures-including acute and long-term phases-were $101 532 for RSV-H (vs $36 302), $48 701 for RSV-ED (vs $27 131), and $28 851 for RSV-PO/HO (vs $20 523); overall RSV-LRTI attributable expenditures thus totaled $65 230, $21 570, and $8327, respectively. Conclusions: The cost of RSV-LRTI requiring hospitalization or ambulatory care among US adults is substantial, and the economic impact of RSV-LTRI may extend well beyond the acute phase of illness.

Systematic Literature Review of Risk Factors for Poor Outcomes Among Adults With Respiratory Syncytial Virus Infection in High-Income Countries.

Identification of risk factors for severe respiratory syncytial virus (RSV) disease in adults could facilitate their appropriate vaccine recommendations. We conducted a systematic literature review (last 10 years in PubMed/Embase) to identify quantitative estimates of risk factors for severe RSV infection outcomes in high-income countries. Severe outcomes from RSV infection included hospitalization, excess mortality, lower respiratory tract infection, or a composite measure: severe RSV, which included these outcomes and others, such as mechanical ventilation and extended hospital stay. Among 1494 articles screened, 26 met eligibility criteria. We found strong evidence that the following increased the risk of severe outcomes: age, preexisting comorbid conditions (eg, cardiac, pulmonary, and immunocompromising diseases, as well as diabetes and kidney disease), and living conditions (socioeconomic status and nursing home residence). The frequency of severe outcomes among younger adults with comorbidities was generally similar to that experienced by older adults, suggesting that immunosenescence and chronic conditions are both contributing factors for elevated risk. Trial registration: PROSPERO (CRD42022315239).

Immune Response to COVID-19 and mRNA Vaccination in Immunocompromised Individuals: A Narrative Review.

Immunocompromised individuals are at high risk of poor coronavirus disease 2019 (COVID-19) outcomes and demonstrate a lower immune response to COVID-19 vaccines, including to the novel mRNA vaccines that have been shown to elicit high neutralizing antibody levels. This review synthesized available data on the immune response to COVID-19 and critically assessed mRNA COVID-19 vaccine immunogenicity in this vulnerable subpopulation. Patients with various immunocompromising conditions exhibit diverse responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 severity and mortality, and available vaccines elicit lower immune responses, particularly in solid organ transplant recipients. Strategies to improve vaccine responses in immunocompromised individuals are being implemented in vaccine recommendations, including the use of a third and fourth vaccine dose beyond the two-dose series. Additional doses may enhance vaccine effectiveness and help provide broad coverage against emerging SARS-CoV-2 variants. Continued investigation of vaccines and dosing regimens will help refine approaches to help protect this vulnerable subpopulation from COVID-19.

Antibiotic prescription in intensive care units in Latin America.

The intensive care units (ICUs) are often considered as the epicenters of antibiotic resistance. Therefore, the total antibiotic consumption is approximately ten fold greater in ICU wards than in general hospital wards. The aim of this study was to evaluate the current use of antibiotics in Latin American ICUs. Three cross-sectional (one-day point) prevalence studies were undertaken in 43 Latin American ICUs. Of 1644 patients admitted, 688 received antibiotic treatment on the days of the study (41.8 %) and, 392 cases (57 %) were due to nosocomial-acquired infections. Of all infections, 22 % (151/688) corresponded to septic shock; and 22 % (151/688) to nosocomial pneumonia (50/151 [33 %], ventilator-associated pneumonia). In 485 patients (70.5 %), cultures were performed before starting antibiotic treatment. The most common microorganisms isolated were extended-spectrum ß-lactamase Enterobacteriaceae, (30.5 %), and Pseudomonas aeruginosa (17 %). Carbapenems (imipenem or meropenem) were the antibiotics most frequently prescribed (151/688, 22 %), followed by vancomycin (103/688, 15 %), piperacillin-tazobactam (86/688, 12.5 %) and broad-spectrum cephalosporins (mainly cefepime) (83/688, 12 %). In summary, carbapenems were the most frequent antibiotics prescribed in Latin American ICUs. This practice seems justified for the high rates of ESBL-producing Gram-negatives found in our patients. Beyond this reason, the problem of bacterial resistance in LA requires that physicians improve the use of carbapenems. The high prevalence of carbapenem-resistant A. baumannii and P. aeruginosa in the region, along with the prevalence of carbapenem-resistant Enterobacteriaceae, have increased markedly. A comprehensive evidence-based stewardship program based on local antimicrobial use and resistance problems should be implemented in our clinical settings.

Burden of invasive group B Streptococcus disease in non-pregnant adults: A systematic review and meta-analysis.

BACKGROUND: Streptococcus agalactiae or group B Streptococcus (GBS) has emerged as an important cause of invasive disease in adults, particularly among the elderly and those with underlying comorbidities. Traditionally, it was recognised as an opportunistic pathogen colonising and causing disease in pregnant women, neonates, and young infants. Reasons for the upsurge of invasive GBS (iGBS) among the elderly remain unclear, although it has been related to risk factors such as underlying chronic diseases, immunosenescence, impaired inflammatory response, and spread of virulent clones. Antibiotics are successfully as treatment or prophylaxis against iGBS. Several candidate vaccines against iGBS are under development. OBJECTIVES: To conduct a systematic review of the current literature on invasive GBS in order to determine disease incidence and case fatality ratio (CFR) among non-pregnant adults. Additionally, information on risk factors, clinical presentation, serotype distribution, and antimicrobial resistance was also retrieved. METHODS: Between January and June 2020, electronic searches were conducted in relevant databases: MEDLINE, EMBASE, Global Health, and SCOPUS. Studies were included in the systematic review if they met the inclusion/exclusion criteria. The authors assessed the selected studies for relevance, risk of bias, outcome measures, and heterogeneity. Meta-analyses on incidence and CFR were conducted after evaluating the quality of methods for assessment of exposure and outcomes. RESULTS: Pooled estimates of iGBS incidence in non-pregnant adults 15 years and older were 2.86 cases per 100.000 population (95% CI, 1.68-4.34). Incidence rates in older adults were substantially higher, 9.13 (95%CI, 3.53-17.22) and 19.40 (95%CI, 16.26-22.81) per 100.000 population ≥50 and ≥ 65 years old, respectively. Incidence rates ranged from 0.40 (95% CI, 0.30-0.60) in Africa to 5.90 cases per 100.000 population (95% CI, 4.30-7.70) in North America. The overall CFR was and 9.98% (95% CI, 8.47-11.58). CFR was highest in Africa at 22.09% (95% CI, 12.31-33.57). Serotype V was the most prevalent serotype globally and in North America accounting for 43.48% (n = 12926) and 46,72% (n = 12184) of cases, respectively. Serotype Ia was the second and serotype III was more prevalent in Europe (25.0%) and Asia (29.5%). Comorbidities were frequent among non-pregnant adult iGBS cases. Antimicrobial resistance against different antibiotics (i.e., penicillin, erythromycin) is increasing over time. CONCLUSIONS: This systematic review revealed that iGBS in non-pregnant adults has risen in the last few years and has become a serious public health threat especially in older adults with underlying conditions. Given the current serotype distribution, vaccines including serotypes predominant among non-pregnant adults (i.e., serotypes V, Ia, II, and III) in their formulation are needed to provide breadth of protection. Continued surveillance monitoring potential changes in serotype distribution and antimicrobial resistance patterns are warranted to inform public health interventions.

Assessing risk factors, mortality, and healthcare utilization associated with Clostridioides difficile infection in four Latin American countries.

BACKGROUND: Clostridioides difficile infection (CDI) is the most common cause of healthcare-associated infections in Western countries. Risk factors, mortality, and healthcare utilization for CDI in Latin America are poorly understood. This study assessed risk factors and burden associated with nosocomial CDI in four Latin American countries. METHODS: This retrospective, case-control study used databases and medical records from 8 hospitals in Argentina, Brazil, Chile, and Mexico to identify nosocomial CDI cases from 2014 - 2017. Cases were patients aged ≥18 years with diarrhea and a positive CDI test ≥72 h after hospital admission. Two controls (without diarrhea; length of hospital stay [LOS] ≥3 days; admitted ±14 days from case patient; shared same ward) were matched to each case. CDI-associated risk factors were assessed by univariate and multivariable analyses. CDI burden (LOS, in-hospital mortality) was compared between cases and controls. RESULTS: The study included 481 cases and 962 controls. Mean age and sex were similar between cases and controls, but mean Charlson comorbidity index (4.3 vs 3.6; p < 0.001) and recent hospital admission (35.3% vs 18.8%; p < 0.001) were higher among cases. By multivariable analyses, CDI risk was associated with prior hospital admission within 3 months (odds ratio [OR], 2.08; 95% CI: 1.45, 2.97), recent antibiotic use (ie, carbapenem; OR, 2.85; 95% CI: 1.75, 4.64), acid suppressive therapy use (OR, 1.71; 95% CI: 1.14, 2.58), and medical conditions (ie, renal disease; OR, 1.48; 95% CI: 1.19, 1.85). In-hospital mortality rate (18.7% vs 6.9%; p < 0.001) and mean overall LOS (33.5 vs 18.8 days; p < 0.001) were higher and longer, respectively, in cases versus controls. CONCLUSION: Antibiotic exposure, preexisting medical conditions, and recent hospital admission were major risk factors for CDI in Argentina, Brazil, Chile, and Mexico. CDI was associated with increased in-hospital risk of death and longer LOS. These findings are consistent with published literature in Western countries.

Evaluation of COVID-19 vaccine breakthrough infections among immunocompromised patients fully vaccinated with BNT162b2.

OBJECTIVE: To evaluate COVID-19 vaccine breakthrough infections among immunocompromised (IC) individuals. METHODS: Individuals vaccinated with BNT162b2 were selected from the US HealthVerity database (10 December 2020 to 8  July 2021). COVID-19 vaccine breakthrough infections were examined in fully vaccinated (≥14 days after 2nd dose) IC individuals (IC cohort), 12 mutually exclusive IC condition groups, and a non-IC cohort. IC conditions were identified using an algorithm based on diagnosis codes and immunosuppressive (IS) medication usage. RESULTS: Of 1,277,747 individuals ≥16 years of age who received 2 BNT162b2 doses, 225,796 (17.7%) were identified as IC (median age: 58 years; 56.3% female). The most prevalent IC conditions were solid malignancy (32.0%), kidney disease (19.5%), and rheumatologic/inflammatory conditions (16.7%). Among the fully vaccinated IC and non-IC cohorts, a total of 978 breakthrough infections were observed during the study period; 124 (12.7%) resulted in hospitalization and 2 (0.2%) were inpatient deaths. IC individuals accounted for 38.2% (N = 374) of all breakthrough infections, 59.7% (N = 74) of all hospitalizations, and 100% (N = 2) of inpatient deaths. The proportion with breakthrough infections was 3 times higher in the IC cohort compared to the non-IC cohort (N = 374 [0.18%] vs. N = 604 [0.06%]; unadjusted incidence rates were 0.89 and 0.34 per 100 person-years, respectively. Organ transplant recipients had the highest incidence rate; those with >1 IC condition, antimetabolite usage, primary immunodeficiencies, and hematologic malignancies also had higher incidence rates compared to the overall IC cohort. Incidence rates in older (≥65 years old) IC individuals were generally higher versus younger IC individuals (<65). LIMITATIONS: This retrospective analysis relied on coding accuracy and had limited capture of COVID-19 vaccine receipt. CONCLUSIONS: COVID-19 vaccine breakthrough infections are rare but are more common and severe in IC individuals. The findings from this large study support the FDA authorization and CDC recommendations to offer a 3rd vaccine dose to increase protection among IC individuals.

Tigecycline in the treatment of ventilator-associated pneumonia: experience from the Latin American Tigecycline Use Registry.

OBJECTIVE: The aim of this study was to evaluate the clinical success rate of the patients with ventilator-associated pneumonia (VAP) treated with tigecycline. METHODS: Data from patients with established criteria of VAP were collected using a web-based reporting system from 16 February, 2006 to June 23, 2009. One hundred and seventeen patients coming from 10 ICUs from Argentina were studied. RESULTS: Overall, attending physician reported clinical success in 74 patients (63%; 95%CI 54.08-72.41%). Global mortality proportion was 33% (39/117 patients). Patients with APACHE II score at admission > or = 15 showed a clinical success rate significantly lower and a mortality rate significantly higher than those with APACHE II score at admission less than 15 (52.6% [30/57] vs 73.3% [44/60]; p 0.0332, and 45.6% [26/57]vs 21.7% [13/60]; p 0.0108). The etiology of VAP was established in 60 patients (51%). Acinetobacter spp. (59%; in 84% of cases carbapenems-resistant), and methicillin-resistant Staphylococcus aureus (22%) were the most common microorganisms isolated. Eleven patients (1.5%) had VAP with bacteremia (respiratory sample and blood cultures positive for the same pathogens). CONCLUSIONS: As initial evidence, our results suggest that tigecycline may be an acceptable alternative for therapy in patients with VAP. Nevertheless, only controlled clinical trials will provide the evidence to support approval for new indications.

[Updated acute community-acquired pneumonia in adults: Guidelines for initial antimicrobial therapy based on local evidence from the South American Working Group (ConsenSur II)]. / Neumonía aguda adquirida en la comunidad en adultos: Actualización de los lineamientos para el tratamiento antimicrobiano inicial basado en la evidencia local del Grupo de Trabajo de Sudamérica (ConsenSur II).

Community-acquired pneumonia (CAP) in adults is probably one of the infections affecting ambulatory patients for which the highest diversity of guidelines has been written worldwide. Most of them agree in that antimicrobial therapy should be initially tailored according to either the severity of the infection or the presence of comorbidities and the etiologic pathogen. Nevertheless, a great variability may be noted among the different countries in the selection of the primary choice in the antimicrobial agents, even for the cases considered as at a low-risk class. This fact may be due to the many microbial causes of CAP and specialties involved, as well as the different health-care systems effecting on the availability or cost of antibiotics. However, many countries or regions adopt some of the guidelines or design their own recommendations regardless of the local data, probably because of the scarcity of such data. This is the reason why we have developed a guideline for the initial treatment of CAP by 2002 upon the basis of several local evidences in South América (ConsenSur I). However, several issues deserve to be currently rediscussed as follows: certain clinical scores other than the Physiological Severity índex (PSI) have become more popular in clinical practice (i.e. CURB-65, CRB-65); some pathogens have emerged in the región, such as community-acquired methicillin resistant Staphylococcus aureus (CA-MRSA) and Legionella spp; new evidences on the performance of the rapid test for the etiologic diagnosis in CAP have been reported (eg. urinary Legionella andpneumococcus antigens); new therapeutic considerations needs to be approached (i.e. dosage reformulation, duration of treatment, emergence of novel antibiotics and clinical impact of combined therapy). Like in the first versión of the ConsenSur (ConsenSur I), the various current guidelines have helped to organize and stratify the present proposal, ConsenSur II.

Surgical site infection in elective clean and clean-contaminated surgeries in developing countries.

BACKGROUND: Surgical site infection (SSI) is both the most frequently studied healthcare-associated infection and the most common healthcare-associated infection in the developing world. A systematic review and meta-analysis was conducted to evaluate the relative size of this burden and to estimate the prevalence of SSI in clean and clean-contaminated surgeries in a large sample of countries in the developing world. METHODS: A systematic search of the MEDLINE/PubMed, Scopus, and LILACS databases was conducted to identify studies providing the prevalence of SSI in elective clean and clean-contaminated surgeries in 39 countries or regions around the world. Data of interest were limited to publications from January 2000 to December 2017. Studies with information on the number of cases of SSI and number of total elective clean and clean-contaminated surgeries during the same period were included in this evaluation. Studies lacking clear definition of the total number of exposed patients were excluded. RESULTS: Based on the combined data from the 99 articles evaluated in this analysis, the overall prevalence of SSI in elective clean and clean-contaminated surgeries was estimated to be 6% (95% confidence interval (CI) 5-7%). This increased to 15% (95% CI 6-27%) when considering only those reports with post-discharge surveillance data. The overall prevalence of SSI in Africa/Middle East, Latin America, Asia, and China was 10% (95% CI 6-15%), 7% (95% CI 5-10%), 4% (95% CI 4-5%), and 4% (95% CI 2-6%), respectively. Significant variability in the data was confirmed by both the funnel plot and the Egger test (p=0.008). CONCLUSIONS: Although the data are variable, it is clear that the incidence of SSI in the developing world is higher than that in the developed world.

Clostridium difficile-associated Diarrhea in Developing Countries: A Systematic Review and Meta-Analysis.

INTRODUCTION: The prevalence of Clostridium difficile infection is rapidly increasing worldwide, but prevalence is difficult to estimate in developing countries where awareness, diagnostic resources, and surveillance protocols are limited. As diarrhea is the hallmark symptom, we conducted a systematic review and meta-analysis to determine the prevalence and incidence of C. difficile infection in patients in these regions who presented with diarrhea. METHODS: We conducted a systematic literature search of MEDLINE/PubMed, Scopus, and Latin-American and Caribbean Health Sciences Literature databases to identify and analyze data from recent studies providing prevalence or incidence rates of C. difficile-associated diarrhea in developing countries within four regions: Africa-Middle East, developing Asia, Latin America, and China. Our objectives were to determine the current prevalence and incidence density rates of first episodes of C. difficile-associated diarrhea in developing countries. RESULTS: Within the regions included in our analysis, prevalence of C. difficile infection in patients with diarrhea was 15% (95% CI 13-17%) (including community and hospitalized patients), with no significant difference across regions. The incidence of C. difficile infection in 17 studies including this information was 8.5 per 10,000 patient-days (95% CI 5.83-12.46). Prevalence was significantly higher in hospitalized patients versus community patients (p  = 0.0227). CONCLUSION: Our prevalence estimate of 15% is concerning; however, low awareness and inconsistent diagnostic and surveillance protocols suggest this is markedly underestimated. Enhanced awareness and management of C. difficile infection in patients with diarrhea, along with improvements in infection control and surveillance practices, should be implemented to reduce prevalence of C. difficile-associated diarrhea in developing countries. FUNDING: Pfizer Inc.

[Initial use of tigecycline in Argentina]. / Uso inicial de tigeciclina en Argentina.

Tigecycline is a new class of antibiotics active against emerging nosocomial pathogens as methicillin-resistant Staphylococcus aureus, extended spectrum (3-lactamases-producing enterobacteria and multidrug-resistant Acinetobacter sp. It was approved for the treatment of complicated intra-abdominal infections and complicated skin and skin structure infections, but its pharmacological and microbiological profile is attractive to physicians for using it in other pathologies caused by resistant pathogens. The aim of this study was to evaluate in which indications tigecycline was used in Argentinian usual clinical settings during the first months after its launch. We analyzed tigecycline prescriptions in 69 patients with severe infections in 15 institutions. Fifteen patients (21%) received tigecycline for approved indications, and 54 (79%) for off label indications (56%) with scientific support and 23%> with limited or without any scientific support). The most frequent off label use was ventilator associated pneumonia (VAP) (36 patients). The etiology of the infections was established in 61%> of the patients. In all cases the isolated bacteria were multi-drug resistant (MDR) Acinetobacter s/?.-carbapenems included. Our study shows that the off label use of tigecycline is frequent, specially in VAP. One of the reasons could be that for MDR-Acinetobacter sp. -VAP, there are few therapeutic options (for instance: colistin). Physicians must evaluate the benefits/risks to use this antibiotic for indications that lack rigorous scientific support.