Usefulness of betalactam therapy for community-acquired pneumonia in the era of drug-resistant Streptococcus pneumoniae: a randomized study of amoxicillin-clavulanate and ceftriaxone

Empirical antibiotic therapy of community-acquired pneumonia (CAP) has been complicated by the worldwide emergence of penicillin resistance among Streptococcus pneumoniae. The impact of this resistance on the outcome of patients hospitalized for CAP, empirically treated with betalactams, has not been evaluated in a randomized study. We conducted a prospective, randomized trial to assess the efficacy of amoxicillin-clavulanate (2 g/200 mg/8 hr) and ceftriaxone (1 g/24 hr) in a cohort of patients hospitalized for moderate-to-severe CAP. Three-hundred seventy-eight patients were randomized to receive amoxicillin-clavulanate (184 patients) or ceftriaxone (194 patients). Efficacy was assessed on Day 2, after completion of therapy and at long term follow-up. There were no significant differences in outcomes between treatment groups, both in intention-to-treat and per-protocol analysis. Overall mortality was 10.3% for amoxicillin-clavulanate and 8.8% for ceftriaxone (NS). There were 116 evaluable patients with proven pneumococcal pneumonia. Rates of high-level penicillin resistance (MIC of penicillin ≥2 µg/mL) were similar in the two groups (8.2 and 10.2%). Clinical efficacy at the end of therapy was 90.6% for amoxicillin-clavulanate and 88.9% for ceftriaxone (95% C.I. of the difference: -9.3 to +12.7%). No differences in outcomes were attributable to differences in penicillin susceptibility of pneumococcal strains. Sequential i.v./oral amoxicillin-clavulanate and parenteral ceftriaxone were equally safe and effective for the empirical treatment of acute bacterial pneumonia, including penicillin and cephalosporin-resistant pneumococcal pneumonia. The use of appropriate betalactams in patients with penumococcal pneumonia and in the overall CAP population, is reliable at the current level of resistance

Impact of antibiotic resistance on chemotherapy for pneumococcal infections

Over the past three decades, penicillin-resistant pneumococci have emerged worldwide. In addition, penicillin-resistant strains have also decreased susceptibility to other β-lactams (including cephalosporins) and these strains are often resistant to other antibiotic groups, making the treatment options much more difficult. Nevertheless, the present in vitro definitions of resistance to penicillin and cephalosporins in pneumococci could not be appropriated for all types of pneumococcal infections. Thus, current levels of resistance to penicillin and cephalosporin seem to have little, if any, clinical relevance in nonmeningeal infections (e.g., pneumonia or bacteremia). On the contrary, numerous clinical failures have been reported in patients with pneumococcal meningitis caused by strains with MICs ≥ 0.12 μg/ml, and penicillin should never be used in pneumococcal meningitis except when the strain is known to be fully susceptible to this drug. Today, therapy for pneumococcal meningitis should mainly be selected on the basis of susceptibility to cephalosporins, and most patients may currently be treated with high-dose cefotaxime (±) vancomycin, depending on the levels of resistance in the patient's geographic area. In this review, we present a practical approach, based on current levels of antibiotic resistance, for treating the most prevalent pneumococcal infections. However, it should be emphasized that the most appropriate antibiotic therapy for infections caused by resistant pneumococci remains controversial, and comparative, randomized studies are urgently needed to clarify the best antibiotic therapy for these infections

Pro-adrenomedullin usefulness in the management of children with community-acquired pneumonia, a preliminary prospective observational study

BackgroundIn adult population with community acquired pneumonia high levels of pro-adrenomedullin (pro-ADM) have been shown to be predictors of worse prognosis. The role of this biomarker in pediatric patients had not been analyzed to date. The objective of this study is to know the levels of pro-ADM in children with community acquired pneumonia (CAP) and analyze the relation between these levels and the patients¿ prognosis.FindingsProspective observational study including patients attended in the emergency service (January to October 2009) admitted to hospital with CAP and no complications at admission. The values for pro-ADM were analyzed in relation to: need for oxygen therapy, duration of oxygen therapy, fever and antibiotic therapy, complications, admission to the intensive care unit, and length of hospital stay. Fifty patients were included. Ten presented complications (7 pleural effusion). The median level of pro-ADM was 1.0065¿nmol/L (range 0.3715 to 7.2840¿nmol/L). The patients presenting complications had higher levels of pro-ADM (2.3190 vs. 1.1758¿nmol/L, p¿=¿0.013). Specifically, the presence of pleural effusion was associated with higher levels of pro-ADM (2.9440 vs. 1.1373¿nmol/L, p¿<¿0.001).ConclusionsIn our sample of patients admitted to hospital with CAP, pro-ADM levels are related to the development of complications during hospitalization.

Long-term azithromycin therapy in patients with severe chronic obstructive pulmonary disease and repeated pulmonary exacerbations

L’objectiu es determinar si el tractament amb azitromicina a llarg termini redueix la freqüència d’exacerbacions respiratòries en pacients amb malaltia pulmonar obstructiva crònica (MPOC) greu. Estudi retrospectiu observacional que avalua els beneficis clínics del tractament amb azitromicina a llarg termini (500 mg per via oral tres vegades per setmana) durant 12 mesos en pacients amb MPOC greu amb un mínim de 4 exacerbacions agudes (EAMPOC) per any o colonitzats per Pseudomonas aeruginosa. Es comparen amb els 12 mesos previs a l’introducció de l’azitromicina: nombre de EAMPOC, hospitalitzacions i dies d'estada hospitalària. L’azitromicina a llarg termini s’associa a una reducció significativa de EAMPOC, hospitalitzacions i dies d’estada hospitalària en pacients amb EPOC greu independentment de la colonització basal.

Replacement therapy for iron deficiency improves exercise capacity and quality of life in patients with cyanotic congenital heart disease and/or the Eisenmenger syndrome

La teràpia suplementària de ferro millora la capacitat d’exercici i la qualitat de vida en malalts amb una cardiopatia congènita cianòtica i/ o síndrome d’Eisenmenger El dèficit de ferro és una troballa comú en la cardiopatia congènita cianòtica, i pot ser la causa d’una reducció en la capacitat d’exercici. Actualment, està indicada la reposició dels dipòsits de ferro en aquest grup de malalts, éssent les evidències científiques escasses. En el present treball investiguem la seguretat i eficàcia del tractament amb ferro en malalts amb una cardiopatia congènita cianòtica. Per tal motiu, vint-i-cinc malalts amb una cardiopatia congenita cianòtica i dèficit de ferro van ser inclosos de forma prospectiva entre Agost del 2008 i Gener del 2009. El tractament utilitzat fou fumarat ferròs oral, fins a una dosi màxima de 200 mg tres vegades al dia. En l’anàlisi basal i als tres mesos de seguiment es va utilitzar el test de qualitat de vida “CAMPHOR”, el test de la marxa dels 6 minuts i la prova d’esforç amb consum d’oxigen. L’edat mitja fou 39.9+/-10.9 anys, 80% dones. Catorze malalts tenien la síndrome d’Eisenmenger, sis una malaltia cianòtica complexa i cinc circulació de Fontan. Cap d’ells va haver d'interrompre el tractament degut a efectes adversos. Després de tres mesos de tractament, l’hemoglobina (19.0+/-2.9g/dL a 20.4+/-2.7g/dL, p&0.001), ferritina (13.3+/-4.7mug/L a 54.1+/-24.2mug/L, p&0.001) i saturació de transferrina (17.8+/-9.6% a 34.8+/-23.4%, p&0.001) van augmentar significativament. També hi va haver una millora significativa en la puntuació del test de qualitat de vida (20.7+/-10.9 a 16.2+/-10.4, p=0.001) i el test de la marxa (371.7+/-84.7m a 402.8.0+/-74.9m, p=0.001). No es van evidenciar canvis significatius en els valors de consum d’oxigen (40.7+/-9.2% a 43.8+/-12.4%, p=0.15). En definitiva, la teràpia suplementària amb ferro en els malats amb una cardiopatia congènita cianòtica i dèficit de ferro és segura i millora la qualitat de vida i la capacitat funcional. En aquest grup de malalts, per tant, és aconsellable identificar el dèficit de ferro i restaurar-ne els seus dipòsits.