Predictors of mortality and clinical characteristics among carbapenem-resistant or carbapenemase-producing Enterobacteriaceae bloodstream infections in Spanish children.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) are an emerging problem in the paediatric population worldwide with high mortality rates in bloodstream infection (BSI). OBJECTIVES: To evaluate predictors of 30 day mortality in CRE BSI in a paediatric cohort. METHODS: A retrospective observational single-centre study (December 2005-August 2018) was conducted. Cases of CRE BSI in children 0 to 16 years were included. Microbiological identification (MALDI Biotyper) and antimicrobial susceptibility testing (Vitek2® and MicroScan panel NBC44) according to EUCAST breakpoints were performed. PCR OXVIKP® was used to confirm carbapenemase genes (OXA-48, VIM, KPC, NDM). Demographic characteristics, underlying diseases, source of bacteraemia, antimicrobial therapy and outcomes were collected from medical records. Survival analysis to establish predictors of 30 day mortality was performed. RESULTS: Thirty-eight cases were included; 76.3% were hospital-acquired infections and 23.7% related to healthcare. All patients had at least one underlying comorbidity and 52.6% were recipients of an organ transplant. VIM carbapenemase was the predominant mechanism (92.1%). Previous CRE colonization or infection rate was 52.6%. Intestinal tract (26.3%) and vascular catheter (21.1%) were the most common sources of infection. Crude mortality within 30 days was 18.4% (7/38); directly related 30 day mortality was 10.5%. Conditions associated with an increment in 30 day mortality were intensive care admission and inadequate empirical therapy (P < 0.05). Combination-antibiotic targeted treatment and a low meropenem MIC were not related to improved survival. CONCLUSIONS: CRE BSI mortality rate is high. The most important factor related to 30 day survival in our CRE BSI cohort in children was empirical treatment that included at least one active antibiotic.

Bloodstream infection due to Herbaspirillum sp.: case series and review of literature.

Herbaspirillum species are Gram-negative bacteria belonging to the class Betaproteobacteria, order Burkholderiales. The phylogenetic and phenotypic similarities among these groups easily lead to species misidentification. Herbaspirillum bacteraemia is an uncommon clinical entity. The objective of this review is to collect information to contribute to the management of this infection. We describe our own case series and review the cases reported in the literature. Cancer appears as the major underlying disease. The main source of bacteraemia was respiratory. Phenotypic identification methods often misidentify this species. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and molecular methods identify at genus level, but species assignment is not reliable. Herbaspirillum spp. showed a highly susceptible antimicrobial profile. ß-Lactams showed good activity with low MIC values, except ampicillin. All isolates were resistant to colistin, suggesting an intrinsic resistance mechanism. Herbaspirillum spp. is an uncommon pathogen. MALDI-TOF MS or molecular methods are necessary to achieve a reliable genus identification. These species are not multidrug resistant. Piperacillin/tazobactam or ceftazidime might be a good treatment for this microorganism.

Impact of rapid diagnosis of Staphylococcus aureus bacteremia from positive blood cultures on patient management.

We have performed a retrospective, before-after comparison of turnaround time and therapy adjustment parameters before and after the introduction of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) plus mecA polymerase chain reaction (PCR) for the identification of methicillin-resistant Staphylococcus aureus (MRSA) in positive blood cultures. There were 227 episodes of S. aureus bacteremia during the study periods. The pre-MALDI-TOF and post-MALDI-TOF groups included 133 and 94 patients, respectively. The two rapid methods performed sequentially decreased the turnaround time of MRSA identification by nearly 50% (2.06 ± 1.95 vs. 3.95 ± 1.70 days). There was no significant reduction in the length of hospitalization (28.27 ± 32.16 vs. 28.62 ± 28.75 days). In both groups, the adequacy of the empirical antibacterial therapy was similar (59.49% vs. 51.31%), but the optimization of the therapy was more frequent in the post-MALDI-TOF group. Routine implementation of these techniques provides results earlier than conventional methods and increases the proportion of episodes with adequate change of empirical to directed antimicrobial therapy.

Evaluation of a lateral flow immunoassay to detect CTX-M extended-spectrum ß-lactamases (ESBL) directly from positive blood cultures for its potential use in Antimicrobial Stewardship programs.

OBJECTIVE: Bloodstream infections (BSI) caused by extended-spectrum beta-lactamases Enterobacteriaceae (ESBL-E) are associated with high rates of treatment failure and increased mortality, especially when appropriate antimicrobial therapy is delayed. Our aim was to evaluate the anticipation of ESBLs detection and the potential improvement of the time response of the Vitek 2 System (BioMérieux; France). METHODS: We compared this lateral flow immunoassay when used directly on fluid from positive blood cultures to the VITEK2 AST system. We evaluated 80 isolates, 61 tested directly on fluid from positive blood cultures and 19 tested on fluid from blood cultures spiked with known ESBL positive and negative organisms. RESULTS: The concordance between the CTX-LFIA and the reference method (Vitek 2) had a Cohen´s Kappa coefficient of 0.97, indicating a particularly good correlation between both compared methods. CONCLUSIONS: This lateral flow immunoassay can be more rapid than the Vitek 2 for earlier presumptive identification of CTX-M ESBLs and can be useful to anticipate results and the adjustment of antimicrobial therapy.

[Congenital cytomegalovirus infection, is more prevalent in our country in newborns exposed to HIV?] / La infección congénita por citomegalovirus, ¿es más prevalente en nuestro medio en neonatos expuestos al VIH?

OBJECTIVE: Congenital cytomegalovirus infection (cCMV) has been considered more prevalent among HIV-exposed children during pregnancy. Spanish national guidelines recommend the cCMV screening in these newborns. Nowadays, pregnant women have a better control of HIV infection compared to previous decades. We aim to analyze the prevalence and associated risk factors to cCMV in these children. METHODS: A retrospective cross-sectorial study was performed. All newborns exposed to HIV were assisted in a third-level hospital (2014-2020). Epidemiological and clinical data of the mother and newborn were recorded. Shell vial urine culture and/or CRP were performed along the two first weeks of life for the neonatal screening of cCMV. RESULTS: Overall 69 newborns were enrolled. A high proportion (82.4%) of the mothers had been diagnosed with HIV before getting pregnant. All women received ART during the pregnancy. Median T-CD4 lymphocytes before delivery was 641/mm3 (IQR: 480-865) and the viral load was undetectable in 83.6%. Serological test for CMV along the first trimester of pregnancy was performed in 73.5% (positive IgG in 96%). There were no congenital cases of HIV neither cCMV (CI 95%:0-5.3%). CONCLUSIONS: The cCMV prevalence in newborns exposed to HIV was 0%, lower than reported before, probably related to a better and earlier ART during pregnancy, leading to a better immunological status.

Rapid identification of yeasts from positive blood culture bottles by pyrosequencing.

We have developed a rapid protocol for the identification of Candida species from positive blood cultures by combining a simple method for nucleic acid extraction and preparation using microbial storage cardboards with polymerase chain reaction (PCR) and pyrosequencing of a small region of the 18 S rRNA gene. The protocol is robust and easy to implement and can be performed in 4 h. The method was tested against a collection of clinical blood cultures. Agreement of sequence identifications with standard microbiological methods was 100%.

Influenza-like illness in pregnant women during summertime: clinical, epidemiological and microbiological features.

It is not known whether influenza-like illnesses (ILI) in pregnant women caused by influenza virus, specifically, those caused by the 2009 Influenza A H1N1 virus (nH1N1), can be clinically distinguished from those caused by other agents. From 1st July 2009 until 20th September 2009, an observational study including all pregnant women presenting at Hospital Universitario La Paz with an ILI was carried out. A specific reverse-transcriptase polymerase chain reaction (RT-PCR) for nH1N1 in nasopharyngeal swabs was prospectively carried out in all patients. Retrospectively, samples were analysed for multiple respiratory virus panel (RT-PCR microarray). Clinical, demographical and other microbiological variables were evaluated as well. A total of 45 pregnant women with ILI were admitted. Of these, 14 (31.1%) women had nH1N1 infection and 11 with a non-influenza ILI (35.48%) were positive for other viruses (five rhinovirus, four parainfluenza virus, one bocavirus and one adenovirus). In 20 patients, no aetiologic agent was identified. The clinical course of nH1N1 was mild, without deaths or severe complications. No significant differences were found when comparing the clinical presentation and course of patients with and without nH1N1 infection. Six women with nH1N1 infection received oseltamivir. Influenza and non-influenza ILI were clinically indistinguishable among pregnant women. Many ILI in pregnant women remain undiagnosed, despite undergoing an RT-PCR microarray for several respiratory viruses.

Campylobacter fetus peritonitis and bacteremia in a patient undergoing continuous ambulatory peritoneal dialysis.

We report a case of Campylobacter fetus peritonitis and bacteremia in a patient undergoing continuous ambulatory peritoneal dialysis.

[Prolonged treatment with valganciclovir in an infant with congenital cytomegalovirus infection]. / Tratamiento prolongado con valganciclovir en un lactante con infección congénita por citomegalovirus.

Treatment with intravenous ganciclovir for six weeks prevents hearing deterioration in children with symptomatic congenital cytomegalovirus (CMV) infection. Prolonged treatment might be more beneficial, but is associated with the potential side-effects of long-term use of intravenous lines. Oral valganciclovir could be an alternative because of its excellent bio-availability, reaching plasma concentrations similar to those achieved with intravenous ganciclovir in neonates with symptomatic CMV infection. We present a two-month-old girl with congenital CMV infection with central nervous disease involvement, who was treated with intravenous ganciclovir for 15 days followed by oral valganciclovir (30 mg/kg/day in 2 doses) for 6 months. Treatment resulted in adequate ganciclovir plasma levels, suppressed plasma viral load, prevention of hearing deterioration and was well tolerated, with no apparent side-effects.

[Nontuberculous mycobacterial lymphadenitis]. / Adenitis por micobacterias no tuberculosas.

OBJECTIVE: To study the clinical features, epidemiology and outcome of nontuberculous mycobacterial lymphadenitis (NTML). METHODS: A retrospective study was performed on 54 patients under 14 years old diagnosed with atypical mycobacterial lymphadenitis between 1987 and 2004. Inclusion criteria were: (i) positive polymerase chain reaction (PCR) test or culture; (ii) positive sensitin skin test 6 mm above Mantoux; (iii) histopathologic features compatible with mycobacterial infection and/or positive direct smear for acid-fast bacilli, Mantoux reaction less than 15 mm, a normal chest radiograph, absence of exposure to an adult with tuberculosis, negative Mantoux test reactions in family members, and exclusion of other causes of granulomatous adenitis. RESULTS: Fifty-four patients were included in the study. The number of NTML cases increased notably from 1996, coinciding with a decrease in cases of tuberculous adenitis. The mean age was 35 months (range: 14 months-6 years). Submandibular nodes were involved in 22 of 63 cases of adenitis (34.9%) and cervical nodes were involved in 21 (33.3%). In 8/42 patients (19%) the tuberculin skin test was larger than 10 mm. Cultures were positive in 52.9% of the cases (18/34) and PCR in 53.3% (8/15). The most frequently isolated mycobacteria was Mycobacterium avium (61%). Therapy failed in 8/21 patients receiving antibiotics (38%), in 10/13 patients with drainage alone (77%) and in none of the patients who underwent surgery (8/8). CONCLUSIONS: Nontuberculous mycobacterial adenitis has become more frequent in our hospital since 1996. Cultures do not always allow isolation of mycobacteria and the Mantoux test frequently yields false positive results, thus hampering diagnosis. The most effective treatment was surgical excision. Nevertheless, when the surgical approach is difficult or there is postoperative recurrence, pharmacological treatment can be useful.

Bacteraemia due to OXA-48-carbapenemase-producing Enterobacteriaceae: a major clinical challenge.

Bacteraemia due to carbapenemase-producing Enterobacteriaceae is an emerging medical problem. Management of this entity is complicated by the difficulty in identifying resistance patterns and the limited therapeutic options. A cohort study was performed including all episodes of bloodstream infection due to OXA-48-producing Enterobacteriaceae (O48PE), occurring between July 2010 and April 2012. Data on predisposing factors, clinical presentation, therapy and outcome were collected from medical records. There were 40 cases of bacteraemia caused by O48PE, 35 Klebsiella pneumoniae and five Escherichia coli. Patients were elderly with significant comorbidities (57.5% underlying malignancy). Thirty-five cases (87.5%) were nosocomial, and five (12.5%) were healthcare-associated. Patients had frequently been exposed to antibiotics and to invasive procedures during hospitalization. The most common source of bacteraemia was the urinary tract followed by deep intra-abdominal surgical site infection. Clinical presentation was severe sepsis or shock in 18 cases (45%). Extended-spectrum ß-lactamase production was detected in 92.5% of isolates. MIC(90) for ertapenem, imipenem and meropenem were 32, 16 and 16 mg/L, respectively. Most frequently preserved antibiotics were amikacin, colistin, tigecycline and fosfomycin. These antibiotics combined are the basis of targeted therapies, including carbapenem in selected cases. Median delay in starting clinically adequate and microbiologically appropriate treatment was 3 days. Crude mortality during admission and within 30 days from bacteraemia was 65% and 50%, respectively. Bloodstream infections caused by O48PE have a poor prognosis. Delay in diagnosis and in initiation of optimal antimicrobial therapy is frequent. Suspicion and rapid identification could contribute to improving outcomes.

Prosthetic mitral valve endocarditis due to Ochrobactrum anthropi: case report.

We describe a case of infective endocarditis in a prosthetic mitral valve due to Ochrobactrum anthropi. Although O. anthropi is an emerging pathogen in immunocompromised patients, infections with the bacterium have very rarely been documented in healthy hosts, and endocarditis is rare. To our knowledge, only two cases of O. anthropi endocarditis have been reported in the medical literature.

Tratamiento prolongado con valganciclovir en un lactante con infección congénita por citomegalovirus / Prolonged treatment with valganciclovir in an infant with congenital cytomegalovirus infection

El tratamiento con ganciclovir intravenoso durante 6 semanas previene el desarrollo de hipoacusia progresiva en los niños con infección congénita sintomática por citomegalovirus (CMV). Un tratamiento más prolongado podría obtener mayores beneficios, aunque presenta el inconveniente de los efectos adversos de un acceso venoso prolongado. El valganciclovir oral puede ser una buena alternativa debido a su excelente biodisponibilidad, lo que permite conseguir concentraciones plasmáticas similares a las alcanzadas con ganciclovir intravenoso. A continuación se presenta el caso de una lactante de 2 meses con infección congénita por CMV, con afectación del sistema nervioso central, que se trató con ganciclovir intravenoso durante 15 días, y posteriormente con valganciclovir oral (30mg/kg/día en 2 dosis) hasta completar 6 meses. El tratamiento fue bien tolerado, sin que se apreciaran efectos adversos significativos. Se obtuvieron concentraciones adecuadas de ganciclovir en plasma y se consiguió la supresión de la carga viral plasmática y la prevención de sordera progresiva (AU)

Treatment with intravenous ganciclovir for six weeks prevents hearing deterioration in children with symptomatic congenital cytomegalovirus (CMV) infection. Prolonged treatment might be more beneficial, but is associated with the potential side-effects of long-term use of intravenous lines. Oral valganciclovir could be an alternative because of its excellent bio-availability, reaching plasma concentrations similar to those achieved with intravenous ganciclovir in neonates with symptomatic CMV infection. We present a two-month-old girl with congenital CMV infection with central nervous disease involvement, who was treated with intravenous ganciclovir for 15 days followed by oral valganciclovir (30mg/kg/day in 2 doses) for 6 months. Treatment resulted in adequate ganciclovir plasma levels, suppressed plasma viral load, prevention of hearing deterioration and was well tolerated, with no apparent side-effects (AU)

Adenitis por micobacterias no tuberculosas / Nontuberculous mycobacterial lymphadenitis

Objetivo Estudiar las características epidemiológicas, clínicas y evolutivas de las linfadenitis por micobacterias no tuberculosas. Métodos Estudio retrospectivo de 54 pacientes menores de 14 años diagnosticados de linfadenitis por micobacterias atípicas entre 1987 y 2004. Los criterios de inclusión fueron: a) reacción en cadena de la polimerasa (PCR) o cultivo positivo; b) test de sensitinas positivo con valor superior en 6 mm al Mantoux, y c) hallazgos anatomopatológicos compatibles con infección micobacteriana, junto con Mantoux menor de 15 mm, radiografía de tórax normal, ausencia de contacto tuberculoso, Mantoux negativo en familiares directos, y exclusión de otras causas de adenitis granulomatosa. Resultados Se detectaron 54 casos de adenitis por micobacterias no tuberculosas. Estas infecciones aumentaron desde 1996 coincidiendo con una disminución de adenitis tuberculosas. La edad media de los pacientes fue de 35 meses (rango: 14 meses-6 años). La localización más frecuente fue submaxilar en 22 de 63 adenitis (34,9 %) y laterocervical en 21 adenitis (33,3 %). El Mantoux fue superior a 10 mm en 8/42 (19 %). El cultivo fue positivo en 18/34 de los casos (52,9 %) y la PCR en 8/15 (53,3 %). La micobacteria más aislada fue Mycobacterium avium (61 %). Se produjo fracaso terapéutico en 8 de los 21 pacientes tratados inicialmente con antibióticos (38 %) y en 10 de los 13 tratados con drenaje (77 %). En el 100 % (8/8) de los casos en los que se realizó exéresis quirúrgica se consiguió la curación definitiva. Conclusiones Los casos de adenitis por micobacterias no tuberculosas han aumentado desde 1996 en nuestro hospital. La rentabilidad de los cultivos es baja y el Mantoux presenta falsos positivos con frecuencia, lo cual dificulta el diagnóstico. La exéresis quirúrgica fue el tratamiento más eficaz. Sin embargo, en adenitis que presenten difícil abordaje quirúrgico y en recurrencias postexéresis el tratamiento farmacológico puede ser útil

Objective To study the clinical features, epidemiology and outcome of nontuberculous mycobacterial lymphadenitis (NTML). Methods A retrospective study was performed on 54 patients under 14 years old diagnosed with atypical mycobacterial lymphadenitis between 1987 and 2004. Inclusion criteria were: (i) positive polymerase chain reaction (PCR) test or culture; (ii) positive sensitin skin test 6 mm above Mantoux; (iii) histopathologic features compatible with mycobacterial infection and/or positive direct smear for acid-fast bacilli, Mantoux reaction less than 15 mm, a normal chest radiograph, absence of exposure to an adult with tuberculosis, negative Mantoux test reactions in family members, and exclusion of other causes of granulomatous adenitis. Results Fifty-four patients were included in the study. The number of NTML cases increased notably from 1996, coinciding with a decrease in cases of tuberculous adenitis. The mean age was 35 months (range: 14 months-6 years). Submandibular nodes were involved in 22 of 63 cases of adenitis (34.9 %) and cervical nodes were involved in 21 (33.3 %). In 8/42 patients (19 %) the tuberculin skin test was larger than 10 mm. Cultures were positive in 52.9 % of the cases (18/34) and PCR in 53.3 % (8/15). The most frequently isolated mycobacteria was Mycobacterium avium (61 %). Therapy failed in 8/21 patients receiving antibiotics (38 %), in 10/13 patients with drainage alone (77 %) and in none of the patients who underwent surgery (8/8). Conclusions Nontuberculous mycobacterial adenitis has become more frequent in our hospital since 1996. Cultures do not always allow isolation of mycobacteria and the Mantoux test frequently yields false positive results, thus hampering diagnosis. The most effective treatment was surgical excision. Nevertheless, when the surgical approach is difficult or there is postoperative recurrence, pharmacological treatment can be useful