Prevalence of dihydropteroate synthase genotypes before and after the introduction of combined antiretroviral therapy and their influence on the outcome of Pneumocystis pneumonia in HIV-1-infected patients.

The objective of this study was to determine whether the prevalence of Pneumocystis jirovecii dihydropteroate synthase (DHPS) gene mutations has changed since the introduction of combined antiretroviral therapy (cART) and whether the mutations are associated with poor outcome in Spanish HIV-1-infected patients with Pneumocystis pneumonia (PcP). We studied 167 PcP episodes in HIV-1-infected patients diagnosed during the pre-cART (1989-1995) and cART (2001-2004) periods. Molecular genotyping of DHPS was successfully performed in 98 patients (43 pre-cART and 55 cART). Seventeen patients (17/98, 17%; 95% confidence interval [CI], 10-25%) had mutations in the DHPS gene: 14 patients (14/43, 33%; 95% CI, 19-49%) from the pre-cART period and 3 patients (3/55, 5.5%; 95% CI, 1.3-16%) from the cART period (P < 0.01). In the multivariate analysis, the pre-cART period, previous PcP prophylaxis with sulfa drugs, and homosexuality as an HIV risk factor were found to be associated with a higher risk of presenting DHPS mutations. Overall, 95% of patients were treated with trimethoprim and sulfamethoxazole (TMP-SMX). In-hospital mortality was similar in patients with (out) mutations (6% versus 11%, P = 0.84). DHPS gene mutations were more common during the pre-cART period and were associated with previous sulfa exposure and homosexuality. However, their presence did not worsen prognosis of PcP. The response to TMP-SMX with therapeutic doses was successful in most cases.

D225G mutation in the hemagglutinin protein found in 3 severe cases of 2009 pandemic influenza A (H1N1) in Spain.

From 27 April to 16 December 2009, we analyzed the hemagglutinin gene sequence of 2009 pandemic influenza A (H1N1) virus in 189 respiratory specimens. We only found the D225G mutation in 3 severe cases. However, it was not found in samples from other cases with or without clinical criteria of severity. The biologic significance of this mutation remains still unclear.

Pneumocystis jirovecii pneumonia in Spanish HIV-infected patients in the combined antiretroviral therapy era: prevalence of dihydropteroate synthase mutations and prognostic factors of mortality.

The incidence of Pneumocystis jirovecii pneumonia (PCP) in HIV-infected patients has decreased thanks to sulfa prophylaxis and combined antiretroviral therapy. The influence of P. jirovecii dihydropteroate synthase (DHPS) gene mutations on survival is controversial and has not been reported in Spain. This prospective multicenter study enrolled 207 HIV-infected patients with PCP from 2000 to 2004. Molecular genotyping was performed on stored specimens. Risk factors for intensive care unit (ICU) admission and mortality were identified using a logistic regression model. Seven patients (3.7%; 95% confidence interval [CI], 1.5-7.5%) had DHPS mutations. Overall mortality was 15% (95% CI, 10-21%), rising to 80% (95% CI, 61-92%) in patients requiring mechanical ventilation. None of the patients with DHPS mutants died, nor did they need ICU admission or mechanical ventilation. PaO(2) <60 mm Hg at admission was a predictor of ICU admission (P = 0.01), and previous antiretroviral therapy predicted non-ICU admission (P = 0.009). PaO(2) <60 mm Hg at admission and ICU admission during the 1st week were predictors of mortality (P = 0.03 and P < 0.001, respectively). The prevalence of DHPS mutants in Spain is low and is not associated with a worse outcome. Severe respiratory failure at admission is the strongest predictor of PCP outcome.

Daptomycin is effective in treatment of experimental endocarditis due to methicillin-resistant and glycopeptide-intermediate Staphylococcus aureus.

Daptomycin is a lipopeptide antibiotic with potent in vitro activity against gram-positive cocci, including Staphylococcus aureus. This study evaluated the in vitro and in vivo efficacies of daptomycin against two clinical isolates: methicillin-resistant S. aureus (MRSA) 277 (vancomycin MIC, 2 microg/ml) and glycopeptide-intermediate S. aureus (GISA) ATCC 700788 (vancomycin MIC, 8 microg/ml). Time-kill experiments demonstrated that daptomycin was bactericidal in vitro against these two strains. The in vivo activity of daptomycin (6 mg/kg of body weight every 24 h) was evaluated by using a rabbit model of infective endocarditis and was compared with the activities of a high-dose (HD) vancomycin regimen (1 g intravenously every 6 h), the recommended dose (RD) of vancomycin regimen (1 g intravenously every 12 h) for 48 h, and no treatment (as a control). Daptomycin was significantly more effective than the vancomycin RD in reducing the density of bacteria in the vegetations for the MRSA strains (0 [interquartile range, 0 to 1.5] versus 2 [interquartile range, 0 to 5.6] log CFU/g vegetation; P = 0.02) and GISA strains (2 [interquartile range, 0 to 2] versus 6.6 [interquartile range, 2.0 to 6.9] log CFU/g vegetation; P < 0.01) studied. In addition, daptomycin sterilized more MRSA vegetations than the vancomycin RD (13/18 [72%] versus 7/20 [35%]; P = 0.02) and sterilized more GISA vegetations than either vancomycin regimen (12/19 [63%] versus 4/20 [20%]; P < 0.01). No statistically significant difference between the vancomycin HD and the vancomycin RD for MRSA treatment was noted. These results support the use of daptomycin for the treatment of aortic valve endocarditis caused by GISA and MRSA.

Human herpesvirus 7 primary infection in kidney transplant recipients.

The aims of the study were to evaluate the incidence and the clinical implications of human herpesvirus (HHV)-7 primary infection in patients undergoing kidney transplantation and the probable interactions between the three beta-herpesviruses (cytomegalovirus [CMV], HHV-6, and HHV-7). Sixty kidney transplant recipients had sequential plasma and whole blood samples collected prior to transplantation and at 7, 14, 21, 28, 45, 60, 75, 90, and 180 days posttransplantation. We used indirect immunofluorescence assays to detect HHV-7 immunoglobulin (Ig) G antibodies in plasma and quantitative real-time polymerase chain reaction to assess CMV, HHV-6 and HHV-7 viral loads. Sixteen out of 60 patients (27%) did not show HHV-7 IgG antibodies prior to transplantation and they were selected for this study. Whereas 3 (18.75%) out of the 16 HHV-7 seronegative patients seroconverted after transplantation, only one patient (6%) had a high HHV-7 viral load from the seventh day posttransplantation in consecutive blood samples during follow-up without clinical manifestations. In our study, the incidence of posttransplant HHV-7 primary infection was low and asymptomatic.

Efficacy of telavancin in the treatment of experimental endocarditis due to glycopeptide-intermediate Staphylococcus aureus.

The efficacy of telavancin, a novel lipoglycopeptide, was evaluated in experimental endocarditis in rabbits using two clinical isolates of glycopeptide-intermediate Staphylococcus aureus: ATCC 700788 and HIP 5836. Infected rabbits were treated for 2 days with telavancin (10 mg/kg of body weight once daily intravenously) or vancomycin (1 g twice daily intravenously), administered with a computer-controlled infusion pump system simulating human serum kinetics. Vegetations were harvested at 16 h postinoculation in the control group and at the end of treatment in the drug-treated group. For ATCC 700788, MICs and minimal bactericidal concentrations (MBCs), respectively, were 1 mg/liter and 4 mg/liter for telavancin and 8 mg/liter and 128 mg/liter for vancomycin. For HIP 5836, MICs and MBCs, respectively, were 4 mg/liter and 8 mg/liter for telavancin and 8 mg/liter and 128 mg/liter for vancomycin. Peak and trough levels were 90 microg/ml and 6 microg/ml, respectively, for telavancin and 46 microg/ml and 6 microg/ml, respectively, for vancomycin. In glycopeptide-intermediate S. aureus ATCC 700788, telavancin sterilized 6 of 16 vegetations (37%), whereas vancomycin sterilized 4 of 20 (20%) (P = 0.29) compared with 0 of 17 in the control group. In HIP 5836 experiments, telavancin and vancomycin sterilized 5 of 16 (31%) and 1 of 15 (7%) vegetations (P = 0.17), respectively, compared with none in the control group. Telavancin reduced vegetation titers by 2.0 and 2.3 logs greater than vancomycin for the ATCC 700788 (4.6 [2.0 to 5.8] versus 6.6 [2.0 to 6.9] log CFU/g vegetation; P = 0.05) and HIP 5836 (4.4 [2.0 to 7.4] versus 6.7 [4.5 to 8.7] log CFU/g vegetation; P = 0.09) strains, respectively; these differences did not reach statistical significance. All isolates from vegetations remained susceptible to telavancin after therapy. The results suggest that telavancin may be an effective treatment for endocarditis caused by glycopeptide-intermediate S. aureus.

The role of viruses in the aetiology of community-acquired pneumonia in adults.

BACKGROUND: The role of viruses in community-acquired pneumonia may have been previously underestimated. We aimed to study the incidence and clinical characteristics of community-acquired pneumonia (CAP) due to respiratory viruses in adults adding PCR to routine conventional laboratory tests. METHODS: Consecutive adult patients diagnosed of CAP from January 2003 to March 2004 were included. Conventional tests including cultures of blood, sputum, urine antigen detection of Streptococcus pneumoniae and Legionella pneumophila, and paired serologies were routinely performed. Nasopharyngeal swabs were processed for study of respiratory viruses through antigen detection by indirect immunofluorescence assay, isolation of viruses in cell culture and detection of nucleic acids by two independent multiplex RT-PCR assays. According to the aetiology, patients were categorized in 4 groups: group 1, only virus detected; group 2, only bacteria detected; group 3, viral and bacterial; and group 4, unkown aetiology. RESULTS: Of 340 patients diagnosed with CAP, 198 had nasopharyngeal swabs available and were included in this study. Aetiology was established in 112 (57%) patients: group 1, n=26 (13%); group 2, n=66 (33%); group 3, n=20 (10%). The most common aetiological agent was S. neumoniae (58 patients, 29%), followed by respiratory viruses (46 patients, 23%). Forty-eight respiratory viruses were identified: influenza virus A (n=16), respiratory syncytial virus A (n=5), adenovirus (n=8), parainfluenza viruses (n=5), enteroviruses (n=1), rhinoviruses (n=8) and coronavirus (n=5). There were two patients coinfected by two respiratory viruses. Serology detected 6 viruses, immunofluorescence 8, viral culture 12, and PCR 45. For the viruses that could be diagnosed with conventional methods, the sensitivity and specificity of RT-PCR was 85% and 92%, respectively. The only clinical characteristic that significantly distinguished viral from bacterial aetiology was a lower number of leukocytes (P=0.004). CONCLUSION: PCR revealed that viruses represent a common aetiology of CAP. There is an urgent need to reconsider routine laboratory tests for an adequate diagnosis of respiratory viruses, as clinical characteristics are unable to reliably distinguish viral from bacterial aetiology.

Salicylate decreases production of AmpC type beta-lactamases and increases susceptibility to beta-lactams in a Morganella morganii clinical isolate.

The effect of salicylate, a marRAB inducer, on the resistance to beta-lactams was characterized in an AmpC beta-lactamase hyperproducer Morganella morganii clinical isolate (the M1 strain). Results were compared with those of the effect of salicylate in a wild-type M. morganii strain. Salicylate induced a decreased susceptibility to nalidixic acid, norfloxacin and tetracycline and simultaneously increased the susceptibility to beta-lactams apparently due to the repression of AmpC beta-lactamase synthesis in the M1 strain. Likewise, salicylate only repressed 46 kDa outer membrane protein expression in the wild-type strain, since the clinical isolate M1 did not express it.

[Usefulness of risk indexes for the prediction of surgical site infection in patients undergoing neurosurgical procedures]. / Utilidad de los índices compuestos de riesgo para predecir el desarrollo de infección quirúrgica en neurocirugía.

BACKGROUND AND OBJECTIVE: The use of risk indexes, originally developed in the US for the assessment of SSI risk, is an useful instrument that must be analyzed according to each specific procedure. The addition of other possible SSI risk factors, like the use of perioperative antibiotic prophylaxis, could improve the predictive value of these indexes. The aim of this study was to determine the SSI incidence rate for craniotomy in patients admitted to the Neurosurgical Unit of the Hospital Clinic of Barcelona (Spain), to assess the use of standard NNIS and SENIC indexes, and to assess the possible effect of the addition of a new risk factor (adequate or inadequate use of perioperative antibiotic prophylaxis) to these indexes. PATIENTS AND METHOD: Risk factors for SSI were assessed following common standard definitions and procedures (CDC-NNIS) over a three-year period (1999-2001). NNIS and SENIC risk indexes were calculated. The effect of the addition of a new variable, namely perioperative antibiotic prophylaxis adequate (0 points) or inappropriate/no prophylaxis (1 point) on these indexes (modified indexes NNISa and SENICa) was also assessed. Statistical analysis included both parametric and non-parametric standard tests. RESULTS: The study included a total of 203 patients undergoing a craniotomy procedure (40% of all neurosurgical procedures). The overall SSI incidence rate was 6.8% (14 patients developed SSI). The cut-off point (75 percentile) for the duration of the procedure was 180 minutes instead of the commonly US reported 240 minutes. Patients who develop SSI had a trend towards having shorter operation times. For those patients in the lower risk groups, the SSI incidence rate was: NNIS (0, 1): 6.9%; SENIC (0, 1): 6.2%. If the modified indexes were used, the SSI incidence rate was: NNISa (0, 1): 4.2%; SENICa (0, 1): 4.9%. When NNIS and SENIC indexes, both standard and modified (NNISa and SENICa), were compared, no statistically significant differences between infected and non-infected patients were observed. CONCLUSIONS: When applied to a health system other than the US, SENIC and NNIS indexes could be useful if adapted to each specific situation and procedure. The added value of a new risk factor (perioperative antibiotic prophylaxis) on standard NNIS and SENIC indexes shows a slight improvement in their prediction rate for SSI in patients undergoing craniotomy, mainly in those patients at lower risk for developing superficial SSI.

Utilidad de los índices compuestos de riesgo para predecir el desarrollo de infección quirúrgica en neurocirugía / Usefulness of risk indexes for the prediction of surgical site infection in patients undergoing neurosurgical procedures

FUNDAMENTO Y OBJETIVO: Los accidentes por exposición a material biológico son los más frecuentes en los trabajadores sanitarios. Entre ellos, las lesiones percutáneas producidas por agujas canuladas son las que se asocian a un mayor riesgo de adquisición de infecciones por microorganismos de transmisión sérica. En este trabajo se describen las exposiciones ocupacionales percutáneas y los factores de riesgo asociados a las causadas por agujas canuladas, recogidos en un sistema de vigilancia multicéntrico nacional. PACIENTES Y MÉTODO: Estudio prospectivo y analítico de las exposiciones percutáneas notificadas al sistema EPINETAC (Exposure Prevention Information Network) en España entre 1996 y 2000. Se realiza un estudio descriptivo de las variables relacionadas con el profesional expuesto, la exposición y su mecanismo de producción, y el paciente fuente de la exposición. Se han calculado las incidencias de exposición por cada 100 camas y por categoría laboral. Se ha realizado un análisis multivariable para conocer los factores de riesgo asociados a las exposiciones por agujas canuladas. RESULTADOS: Se ha declarado un total de 16.374 accidentes percutáneos, el 87 por ciento con aguja canulada. La incidencia de exposiciones ha sido de 11,8 exposiciones por cada 100 camas. Las matronas son el colectivo profesional con mayor riesgo (9 exposiciones por cada 100 matronas). Los factores que se asocian más a los accidentes con aguja canulada han sido los siguientes: categoría laboral de matrona (odds ratio [OR] = 7,5; intervalo de confianza [IC] del 95 por ciento, 4,1-13,7) y estudiantes de enfermería (OR = 2,1; IC del 95 por ciento, 1,2-3,7), reencapuchado de la aguja (OR = 28,8; IC del 95 por ciento, 16,5-50,6), trabajar en el área de extracciones (OR = 3,3; IC del 95 por ciento, 1,2-9,5) y en hemodiálisis (OR = 2,5; IC del 95 por ciento, 1,4-4,3). CONCLUSIONES: La incidencia de exposición ocupacional percutánea en España es similar a la descrita en otros países que usan sistemas de vigilancia comparables. El riesgo de exposición con agujas canuladas está directamente relacionado con la categoría laboral, la experiencia profesional, el área de trabajo y la actividad realizada (AU)

Ciclosporiasis: estudio clinicoepidemiológico en viajeros con Cyclospora cayetanensis importada / Cyclosporiasis: a clinical and epidemiological study in travellers with imported Cyclospora cayetanensis infection

FUNDAMENTO: Conocer las características clínicas y epidemiológicas de la enteritis por Cyclospora cayetanenesis. PACIENTES Y MÉTODO: Protocolo clínico, epidemiológico y microbiológico de estudio en viajeros a países de renta baja. RESULTADOS: Se diagnosticó ciclosporiasis a 55 pacientes. El 96 por ciento consultaron por diarrea del viajero (DV). Las características más llamativas de la DV eran la persistencia de la diarrea (más de 2 semanas de evolución), que afectaba a 38 pacientes (69 por ciento), y una pérdida igual o superior a 3 kg de peso en el 38 por ciento de pacientes de la serie. En el 36 por ciento de los casos la DV se inició después del viaje. Aunque cosmopolita, C. cayetanensis se aisló con más frecuencia en viajeros a América Latina, el subcontinente indio y el sudeste asiático. Sólo en 5 viajeros se detectó algún factor de riesgo potencialmente específico: frambuesas en tres casos, leche de búfalo en uno y ceviche en uno. CONCLUSIONES: C. cayetanensis es un enteropatógeno emergente, que se aísla en un 2 a un 4 por ciento de los pacientes afectados de DV y debe formar parte del diagnóstico diferencial en esta enfermedad (AU)