Carbapenem-resistant organisms (CRO) are a major global public health threat. Enterobacterales hydrolyze almost all β-lactams through carbapenemase production. Infections caused by CRO are challenging to treat due to the limited number of antimicrobial options. This leads to significant morbidity and mortality. Over the last few years, several new antibiotics effective against CRO have been approved.

Despite the high prevalence of penicillin resistance among Streptococcus pneumoniae strains in Spain(40 to 60% with MIC ≥ 0.1 μg/ml), the data on acute otitis media (AOM) isolates are scarce. We conducted a prospective, longitudinal study to determine the rates of antimicrobial resistance of S. pneumoniae isolates from children with AOM in our country and to analyze the effect of previous antibiotic therapy on these rates. Tympanocentesis was performed on 169 children diagnosed with AOM (age range, 1 month to 14 years). Two groups were considered: Group A, 113 patients with non-antibiotictreated AOM, subdivided into Group A1 (collected from 1989 to 1992) and Group A2 (1992 to 1996); Group B, 56 patients from the period 1992 to 1996, with AOM clinical failure, defined as worsening or persistent symptoms after at least 2 days of appropriate antibiotic therapy. Amoxicillinclavulanate was the most frequent antibiotic used (68%), followed by azithromycin (21%), cefaclor and cefixime (11%). A total of 63 S. pneumoniae isolates were recovered, 42 in Group A and 21 in Group B. Resistance to penicillin (MIC ≥ 0.1 μg/ml) was found in 38% of strains in Group A (32% in A1 and 50% in A2), but in Group B the rate of resistance reached 90% (P= 0.0002). Erythromycin resistance was also increased from 35% (Group A2) to 62%(Group B), and trimethoprim-sulfamethoxazole resistance rose from 64% to 81%. Resistance to penicillin among S. pneumoniae AOM isolates is frequent and is increasing in Spain. After failure of standard antibiotic therapy, the rates of penicillin resistance reached 90% of the isolates.

Children are at higher risk of tuberculosis (TB) dissemination and extrapulmonary disease, contributing greatly to TB-associated morbidity and long-term sequelae. However, there are very few studies that assess the impact and clinical spectrum of pediatric extrapulmonary TB (EPTB) in low-prevalence regions. Children <18 years of age diagnosed with TB in Madrid region (2005-2013) were reviewed. We compared the epidemiology, clinical characteristics and the performance of diagnostic tests in childhood extrapulmonary and pulmonary disease. We performed a multivariate logistic regression to identify factors associated with EPTB. During the study period, 93 of 526 pediatric TB cases had EPTB (17.7%). The most common site was lymphatic TB (34.5%). The source case was not identified in most extrapulmonary cases, contrary to pulmonary TB (28% vs. 63.3%; P < 0.001). The tuberculin-skin-test induration was smaller in EPTB cases (<5 mm 22% vs. 5%; P < 0.001), but the sensitivity of interferon-gamma-release-assays was similar (76.9% vs. 79.4%). Children with EPTB presented higher rate of bacteriologic confirmation (66% vs. 49.4%; P < 0.01), and higher incidence of multidrug resistant TB (8.2% vs. 1.6%; P = 0.03). Complications were present in 40.2% extrapulmonary cases. EPTB was associated with the child's foreign origin [odds ratio (OR) 2.3 (1.1-5.3)], immune disorders [OR 5.8 (1.9-17.1)] and drug resistance [OR 2.4 (1.1-5.4)]. In our low-prevalence region, childhood EPTB was linked to immigrant status, immune disorders and drug resistance, and presented high rate of complications. Our study underscores the relevance of improved diagnostic tools and systematic TB screening in high risk populations.

Cytomegalovirus (CMV) is the leading cause of congenital infection worldwide. Data about the management of CMV infection in pregnant women are scarce, and treatment options are very limited. The aim of the study is to investigate the effectiveness of cytomegalovirus hyperimmune globulin (CMV-HIG) for the prevention and treatment of congenital CMV (cCMV) infection. A retrospective observational study was conducted in three tertiary hospitals in Madrid. In the period 2009-2015, CMV-HIG (Cytotect® CP Biotest, Biotest) treatment was offered to all pregnant women with primary CMV infection and/or detection of CMV-DNA in amniotic fluid in participating centers. Women were divided into prevention and treatment groups (PG and TG, respectively). Those with primary CMV infection who had not undergone amniocentesis comprised the PG and received monthly CMV-HIG (100 UI/kg). If CMV-DNA was subsequently detected in amniotic fluid, one extra dose of CMV-HIG (200 UI/kg) was given 4 weeks after the last dose. Those women were considered to be part of the PG group despite detection of CMV-DNA in amniotic fluid. In the case of a negative result in CMV-DNA detection in amniotic fluid or if amniocentesis was not performed, monthly HIG was given up to the end of the pregnancy. Thirty-six pregnant women were included. Median gestational age at birth was 39 weeks (interquartile range: 38-40) and two children (5.5%) were premature (born at 28 and 34 weeks' gestation). Amniocentesis was performed in 30/36 (83.4%) pregnancies and CMV PCR was positive in 21 of them (70%). One fetus with a positive PCR in amniotic fluid that received one dose of HIG after amniocentesis presented a negative CMV-PCR in urine at birth, and was asymptomatic at 12 months of age. Twenty-four children were infected at birth, and 16/21 (76.2%) presented no sequelae at 12 months, while two (9.5%) had a mild unilateral hearing loss and three (14.3%) severe hearing loss or neurological sequelae. Seventeen women were included in the PG and 19 in the TG. In the PG 7/17 (41%) fetuses were infected, one pregnancy was terminated due to abnormalities in cordocentesis and one showed a mild hearing loss at 12 months of age. In the TG, 18/19 children (95%) were diagnosed with cCMV, while the remaining neonate had negative urine CMV at birth. Eight out of the 19 fetuses (42.1%) showed CMV related abnormalities in the fetal US before HIG treatment. Complete clinical assessment in the neonatal period and at 12 months of age was available in 16 and 15 children, respectively. At birth 50% were symptomatic and at 12 months of age, 4/15 (26.7%) showed a hearing loss and 3/15 (20%) neurologic impairment. Fetuses with abnormalities in ultrasonography before HIG presented a high risk of sequelae (odds ratios: 60; 95%CI: 3-1185; p = .007). Prophylactic HIG administration in pregnant women after CMV primary infection seems not to reduce significantly the rate of congenital infection, but is safe and it could have a favorable effect on the symptoms and sequelae of infected fetuses. The risk of long-term sequelae in fetuses without US abnormalities before HIG is low, so it could be an option in infected fetuses with normal imaging. On the other hand, the risk of sequelae among infected fetuses with abnormalities in fetal ultrasonography before HIG despite treatment is high.