DSc (Medicine), Faculty of Health Sciences, University of the Witwatersrand / No abstract present

We are grateful to Centro de Investigacion del Envejecimiento (CIEN) of Universidad San Martin de Porres (USMP) for providing us with the database for the study. To the faculty team of research of the medical school of Universidad de Ciencias Aplicadas (UPC) for their appreciations and comments. Jorge L. Maguiña is a doctoral candidate studying Epidemiological Research at Universidad Peruana Cayetano Heredia under FONDECYT/CIENCIACTIVA scholarship EF033-235-2015 and supported by training grant D43 TW007393 awarded by the Fogarty International Center of the US National Institutes of Health . / El texto completo de este trabajo no está disponible en el Repositorio Académico UPC por restricciones de la casa editorial donde ha sido publicado. / Introduction: Sarcopenia is a geriatric syndrome characterized by loss of muscle mass and strength. The prevalence in people between 60–70 years is about 5–13% and in adults over 80 years, between 11–50% in the USA. Sarcopenia increases the risk of mortality and nosocomial infections. Community-acquired pneumonia is the first infectious-related cause of death in elderly people. However, there is lack of evidence about the association between sarcopenia and pneumonia. The aim of our study was to determine the incidence and risk factors of community-acquired pneumonia in older adults with sarcopenia in a Peruvian hospital. Methods: A retrospective cohort study was conducted in the geriatrics service of Centro Medico Naval “Cirujano Mayor Santiago Tavara”. Sarcopenia was defined by “European Consensus of Sarcopenia” criteria. MultivariatePoisson regression model was conducted to estimate the effect of the independent association between sarcopenia and pneumonia. Results: A total of 1598 subjects were enrolled, 59.0% were male; with a mean age of 78.3 ± 8.6 years. The prevalence of sarcopenia was 15.1% (95% CI: 13.3–16.8) and the incidence of community-acquired pneumonia was 15.14% (95%CI 13.4–16.9). In the multivariate model, we found a higher incidence of pneumonia in sarcopenic compared to non-sarcopenic, RR(a) 3.88 (95% CI: 2.82–5.33). Discussion: Our study showed a higher incidence of community-acquired pneumonia in sarcopenic subject. Results provide information on the importance of detecting this syndrome because it gives us scientific evidence of the interest of a correct comprehensive geriatric assessment in older patients with a high risk of pneumonia. / We are grateful to Centro de Investigacion del Envejecimiento (CIEN) of Universidad San Martin de Porres (USMP) for providing us with the database for the study. To the faculty team of research of the medical school of Universidad de Ciencias Aplicadas (UPC) for their appreciations and comments. Jorge L. Maguiña is a doctoral candidate studying Epidemiological Research at Universidad Peruana Cayetano Heredia under FONDECYT/CIENCIACTIVA scholarship EF033-235-2015 and supported by training grant D43 TW007393 awarded by the Fogarty International Center of the US National Institutes of Health . / Revisión por pares / Revisión por pares

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. Infectious Diseases Society of America considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances. Coccidioidomycosis, also known as San Joaquin Valley fever, is a systemic infection endemic to parts of the southwestern United States and elsewhere in the Western Hemisphere. Residence in and recent travel to these areas are critical elements for the accurate recognition of patients who develop this infection. In this practice guideline, we have organized our recommendations to address actionable questions concerning the entire spectrum of clinical syndromes. These can range from initial pulmonary infection, which eventually resolves whether or not antifungal therapy is administered, to a variety of pulmonary and extrapulmonary complications. Additional recommendations address management of coccidioidomycosis occurring for special at-risk populations. Finally, preemptive management strategies are outlined in certain at-risk populations and after unintentional laboratory exposure.

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. Infectious Diseases Society of America considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances. Coccidioidomycosis, also known as San Joaquin Valley fever, is a systemic infection endemic to parts of the southwestern United States and elsewhere in the Western Hemisphere. Residence in and recent travel to these areas are critical elements for the accurate recognition of patients who develop this infection. In this practice guideline, we have organized our recommendations to address actionable questions concerning the entire spectrum of clinical syndromes. These can range from initial pulmonary infection, which eventually resolves whether or not antifungal therapy is administered, to a variety of pulmonary and extrapulmonary complications. Additional recommendations address management of coccidioidomycosis occurring for special at-risk populations. Finally, preemptive management strategies are outlined in certain at-risk populations and after unintentional laboratory exposure.

Methicillin-resistant Staphylococcus aureus (MRSA) is a successful pathogen which was historically found in hospital settings but now is a common cause of infection in communities. The rapid emergence of community-acquired MRSA (CA-MRSA) at the turn of the 21st century has established this bacterium’s presence throughout the globe and MRSA continues to be endemic in certain countries. Asia is the most populous continent in the world and also holds a high burden of MRSA infection. This presents a concern for both public health and the acquisition of antibiotic resistance in this region. This literature review describes how MRSA became a successful pathogen. It provides a systematic review of the recent literature on MRSA in East Asia to identify major MRSA clones by country as determined by their molecular characteristics. Also to identify notable genetic and epidemiological factors associated with these MRSA clones. The results of this survey provided evidence of the importance of using molecular categorization techniques to accurately distinguish MRSA strains that require specific antibiotic treatment methods. It also provided evidence of CA-MRSA clones invading hospital settings and traditional hospital-acquired MRSA (HA-MRSA) clones continuing to develop multi-drug resistance throughout East Asian countries. The results also detected novel MRSA strains across hospitals and reported the spread of major MRSA clones within and between countries. Strengthening existing surveillance systems and collaborative efforts between countries within Asia should be a priority to monitor the evolution and movement MRSA especially in the age of globalization and accessible travel.

Abstract Systematic analyses of infections in critical illness are sparse and mostly restricted to specific infection categories. Thus, a prospective study was carried out in a medical-surgical ICU during 14 months on patients whose ICU stay was longer than 48 h. The prospectively gathered data included detailed patient history, infection survey, severity of illness scores (APACHE II, SOFA), resource use, short-term and long-term outcome and quality of life following hospital discharge. Altogether 335 patients were included, of whom 251 (74.9%) had an infection on admission; 59.3% had a community-acquired infection (CAI) and 40.7% a hospital-acquired infection (HAI), while 84 (25.1%) did not have any infection (NI). APACHE II scores and ICU or hospital mortality rates did not differ between the groups. The median hospital stay was longer in the HAI than in the CAI or NI groups. Eighty (23.9%) of the 335 patients developed an ICU-acquired infection (48 per 1000 patient days): ventilator-associated pneumonia (VAP) in 33.8% of the cases, central catheter-related (CRI) or primary bloodstream infections in 6.3% and urinary tract infections in 1.3%, while the corresponding device-related incidences per 1000 days were 18.8, 2.2 and 0.5, respectively. ICU-acquired infection was an independent risk factor for hospital mortality. It doubled the risk for hospital mortality in patients with an infection on admission and caused a threefold the risk in patients without an infection on admission and an almost fourfold increase in the use of nursing resources. Of the 272 hospital survivors, 83 (30.5%) died after discharge during the median follow-up of 17 weeks. Infection status on admission or during the ICU stay did not affect long-term mortality. ICU-acquired infection did not have an impact on patients' quality of life. The current general level of health compared to the status before ICU admission did not differ between the groups, either. Only 36% of those employed resumed their previous jobs. Three-fourths of patients had an infection on admission, while nearly one fourth acquired an ICU infection. The high VAP rate suggests a need for re-evaluation of preventive measures, whereas the low CRI indicates more successful prevention. ICU-acquired infection was a significant risk factor for hospital mortality, but did not affect patients' long-term survival or quality of life.

Objective: The main objective of this study was to detect the presence of 14 respiratory viruses and atypical bacteria (Mycoplasma pneumoniae, Chlamydia pneumoniae), via polymerase chain reaction in patients under 18 years old hospitalized due to community-acquired pneumonia (CAP) from Lima, Peru. Results: Atypical pathogens were detected in 40% (58/146); viral etiologies in 36% (52/146) and coinfections in 19% (27/146). The most common etiological agent was M. pneumoniae (n = 47), followed by C. pneumoniae (n = 11). The most frequent respiratory viruses detected were: respiratory syncytial virus A (n = 35), influenza virus C (n = 21) and parainfluenza virus (n = 10). Viral-bacterial and bacterium-bacterium coinfections were found in 27 cases. In our study population, atypical bacteria (40%) were detected as frequently as respiratory viruses (36%). The presence of M. pneumoniae and C. pneumoniae should not be underestimated as they can be commonly isolated in Peruvian children with CAP.

El tracte dels pacients amb pneumonia adquirida en la comunitat (PNAC) que no responen al tractament antibiòtic inicial constitueix un repte per al clínic. Aquest estudi va investigar la utilitat dels canvis en els nivells de la proteïna C reactiva (PCR) per tal de discriminar entre el fracàs terapèuticc vertader i la resposta lenta al tractament. MÈTODES Aquest estudi multicèntric prospectiu observacionasl va investigar el comportament dels nivells de PCR en plasma els dies 1 i 4 en pacients adults hospitalitzats diagnosticats de PNAC. Es determinaren els nivells de PCR en sang els dies 1 i 4. En acabar el procés, els pacients que no respongueren (que no havien assolit l’estabilitat el dia 4), foren classificats en: a) fracàs terapèutic vertader, quan la teràpia antibiòtica s’hagué de canviar i/o es realitzaren procediments terapèutics invasius, o b) resposta lenta al tractament quan s’obtingué l’estabilitat clínica sense canvis respecte al tractament antibiòtic empíric inicial. RESULTATS Al dia 4, 78 (27,4%) de 285 pacients no assoliren l’estabilitat clínica. D’aquests, 56 (71,8%) pacients es curaren sense canvi en el tractament antibiòtic inicial (mortalitat del 0,0%), i en 22 (28,2%) pacients, el tractament inicial s’hagué de modificar (mortalitat 40,9%). Al dia 4, els nivells de PCR davallaren en 52 (92,9%) pacients amb resposta lenta al tractament i només en 7 (31,8%) pacients amb fracàs terapèutic vertader (p < 0,001). Un model desenvolupat que inclogué els valors de PCR i els de la freqüència respiratòria al dia 4, identificà els pacients amb fracàs terapèutic vertader. L’àrea sota la corba ROC obtinguda amb aquest model fou de 0,87 (IC 95% , 0,780 a 0,966). CONCLUSIÓ Els canvis dels valors de PCR són útils per a discriminar entre el fracàs terapèutic vertader i la resposta lenta al tractament, i poden ajudar el clínic a prendre decisions en el tracte dels pacients amb PNAC que no milloren. / INTRODUCCION El manejo de los pacientes con neumonía adquirida en la comunidad (NAC) que no responden al tratamiento antibiótico inicial constituye un reto para el clínico. Este estudio investigó la utilidad de los cambios en los niveles de la proteína C reactiva (PCR) para discriminar entre fracaso terapéutico verdadero y respuesta lenta al tratamiento. METODOS Este estudio multicéntrico prospectivo observacional, investigó el comportamiento de los niveles de PCR en plasma en los días 1 y 4 en pacientes adultos hospitalizados con diagnóstico de NAC . Se determinaron los niveles de PCR en sangre los días 1 y 4. Al finalizar el proceso, los pacientes no respondedores (que no habían alcanzado la estabilidad para el día 4) fueron clasificados en a) fracaso terapéutico verdadero, cuando la terapia antibiótica tuvo que ser cambiada y/o se realizaron procedimientos terapéuticos invasivos; o b) respuesta lenta al tratamiento cuando se alcanzó la estabilidad clínica sin cambios respecto al tratamiento antibiótico empírico inicial. RESULTADOS Al día 4, 78 (27,4%) de 285 pacientes no alcanzaron la estabilidad clínica. De estos, 56 (71,8%) pacientes se curaron sin cambio del tratamiento antibiótico inicial (mortalidad de 0,0%); y en 22 (28,2%) pacientes el tratamiento antibiótico inicial tuvo que ser modificado (mortalidad 40,9%). Al día 4, los niveles de PCR descendieron en 52 (92,9%) pacientes con respuesta lenta al tratamiento y solo en 7 (31,8%) pacientes con fracaso terapéutico verdadero (p<0.001). Un modelo desarrollado que incluyó los valores de PCR y los de la frecuencia respiratoria al día 4, identificó a los pacientes con fracaso terapéutico verdadero. El área bajo la curva ROC obtenida con este modelo fue de 0,87 (IC 95%, 0,780 a 0,966). CONCLUSION Los cambios de los valores de PCR son útiles para discriminar entre el fracaso terapéutico verdadero y la respuesta lenta al tratamiento; y pueden ayudar al clínico a tomar decisiones en el manejo de los pacientes con NAC que no mejoran. / BACKGROUND The management of patients with community-acquired pneumonia (CAP) who fail to improve constitutes a challenge for clinicians. This study investigated the usefulness of C-reactive protein (CRP) changes in discriminating true treatment failure from slow response to treatment. METHODS This prospective multicenter observational study investigated the behavior of plasma CRP levels on days 1 and 4 in hospitalized patients with CAP.We identified non-responding patients as those who had not reached clinical stability by day 4. Among them, true treatment failure and slow response situations were defined when initial therapy had to be changed or not after day 4 by attending clinicians, respectively. RESULTS By day 4, 78 (27.4%) out of 285 patients had not reached clinical stability. Among them, 56 (71.8%) patients were cured without changes in initial therapy (mortality 0.0%), and in 22 (28.2%) patients, the initial empirical therapy needed to be changed (mortality 40.9%). By day 4, CRP levels fell in 52 (92.9%) slow responding and only in 7 (31.8%) late treatment failure patients (p<0.001). A model developed including CRP behavior and respiratory rate at day 4 identified treatment failure patients with an area under the Receiver Operating Characteristic curve of 0.87 (CI 95%, 0.78–0.96). CONCLUSION Changes in CRP levels are useful to discriminate between true treatment failure and slow response to treatment and can help clinicians in management decisions when CAP patients fail to improve

Staphylococcus aureus is one of the most important pathogens both in community- or hospital-acquired infections. The first part of this study analyzed the similarity of molecular types of S. aureus isolates cultured from nares and blood in patients with S. aureus bacteremia (SAB) by pulse-fielded gel electrophoresis (PFGE) of digested chromosomal DNA by Sma I at Kaohsiung Veterans General Hospital from August 1, 2000 through July 31, 2001. The results showed that the PFGE types of 78 (82.1%) paired nare and blood isolates of the 95 SAB patients having nasal carriage of S. aureus were clonally identical; identical in 89.7% patients of nosocomial group and 62.9% in community-acquired group. This provides the powerful evidence in close relationship between nasal carriage of S. aureus and acquisition of it in bacteremia. The data also showed that the rate of methicillin resistance occurred in SAB patients with nasal carriage in isolates of nosocomial SAB was 85.3%, and 31.3% in community-acquired group. The second part of this study analyzed the distribution of PFGE types of 163 nosocomial SAB isolates. The most predominant type was type A and composed 51.5% (84 strains) of 163 nosocomial SAB isolates. They were further divided into 7 subtypes. The second prevailing type was type B, 6.1%(10 strains). The evidence that an endemic stain (type A) occurred in >50% of nosocomial bacteremic isolates demonstrates horizontal dissemination of a single endemic strain of S. aureus in the SAB patients was common in the hospital. These results provide support for strategies to endorse more intensive procedures in infection control and to prevent systemic S. aureus infections by eliminating S. aureus nasal carriage.

Staphylococcus aureus is a bacterial pathogen that is believed to be the most common agent of human infectious disease, causing conditions ranging from common skin lesions to life-threatening illnesses. S. aureus has also shown a remarkable ability to develop resistance to antimicrobial treatment, making infections difficult to treat. In the post-genomic era, proteomic studies analyzing the protein complement of a genome in a particular organism at any given time, have gained real significance. This result is largely due to dynamic changes in protein expression profiles which can lead wide alterations in physiology and behavior. For proteomics, it is necessary to maximize protein concentration and to devise a method that can be easily employed and provide reproducible results. Most proteomic studies of S. aureus involve 2D gel electrophoresis (2-DE); however, 2-DE has many drawbacks. Proteins that are too large, hydrophobic, acidic, or basic are poorly resolved. Multi-dimensional protein identification (MudPIT) allows complex protein samples to be analyzed in solution. As yet, there has not been a study involving solely 2D liquid chromatography followed by mass spectrometric analysis in S. aureus ; therefore we sought to catalogue the intracellular proteome and secretome of a commonly used and well-studied lab strain, SH1000. This was conducted during post-exponential and stationary phases of growth so as to understand its adaptation over time by utilizing differential protein synthesis. We found cytoplasmic proteins involved in glycolysis to be highly expressed in post-exponential phase while proteins involved in tricarboxylic acid cycle to be prevalent in stationary phase. We also found production of agr-regulated secreted toxins and proteases to be upregulated in stationary phase. In addition to this we employed proteomic approaches to quantitatively profile the secretomes of leading clinical isolates of S. aureus, as such a study is currently lacking. These included the two most common hospital-associated S. aureus strains (USA100 and USA200), and the two most common community-associated S. aureus strains (USA300 and USA400). We found agr-regulated proteins are generally upregulated in CA-MRSA strains USA300 and USA400 and surface-associated proteins to be upregulated in HA-MRSA strains USA100 and USA200. This finding concurs with literature regarding transcriptomic studies showing a hyperactive agr in CA-MRSA strains compared to HA-MRSA strains.