Ignacio Obando

Successful management of chronic multifocal Q fever Osteomyelitis with adjuvant interferon-gamma therapy.

We present a 3-year-old girl who had chronic recurrent multifocal osteomyelitis caused by Coxiella burnetii despite long-term dual antibiotic therapy. Excellent clinical response was achieved and sustained when immunomodulatory therapy with interferon-γ was initiated. This is the case of a first child who was successfully treated with interferon-γ as adjuvant therapy for chronic multifocal Q fever osteomyelitis.

Diagnostic and therapeutic challenges in a child with complete Interferon-γ Receptor 1 deficiency

Autosomal recessive (AR) complete Interferon‐γ Receptor1 (IFN‐γR1) deficiency is a rare variant of Mendelian susceptibility to mycobacterial disease (MSMD). Although hematopoietic stem cell transplantation (HSCT) remains the only curative treatment, outcomes are heterogeneous; delayed engraftment and/or graft rejection being commonly observed. This case report and literature review expands the knowledge about this rare but potentially fatal pathology, providing details regarding diagnosis, antimicrobial treatment, transplant performance, and outcome that may help to guide physicians caring for patients with AR complete IFN‐γR1 or IFN‐γR2 deficiency. Pediatr Blood Cancer

Uso prudente de antibióticos y propuestas de mejora desde la medicina hospitalaria

The largest consumption of antimicrobials is concentrated in hospitals and within them, the intensive care units. The quality of antimicrobial use is not optimal, with up to 50% of prescriptions being unnecessary or inappropriate. Inappropriate antibiotic use leads to severe consequences, such as increased patient mortality and morbidity and bacterial resistance. The primary reason for inappropriate use is the insufficient knowledge of the increasingly vast and complex information about the diagnosis and treatment of infectious diseases. There is general agreement on the need to improve the use of antimicrobials in hospitals but not on how to improve it. University Hospital Virgen del Rocío (Seville) has launched the Institutional Programme for the Optimisation of Antimicrobial Treatment (PRIOAM), inspired by the recommendations of the Infectious Diseases Society of America and adapted to the structural, functional and cultural characteristics of the hospital. PRIOAM is coordinated by a multidisciplinary team chosen by the Committee on Infections and Antimicrobials and has three basic characteristics: it is an institutional programme that has incentives linked to achieving goals; it is an educational programme in which training and knowledge are the basis for the proper use of antimicrobials; and it is a programme subject to results, in which the main objectives are clinical, not economic, to reduce mortality and morbidity in patients with infections and to delay the development of resistance.The largest consumption of antimicrobials is concentrated in hospitals and within them, the intensive care units. The quality of antimicrobial use is not optimal, with up to 50% of prescriptions being unnecessary or inappropriate. Inappropiate antibiotic use leads to severe consequences, such as increased patient mortality and morbidity and bacterial resistance. The primary reason for inappropriate use is the insufficient knowledge of the increasingly vast and complex information about the diagnosis and treatment of infectious diseases. There is general agreement on the need to improve the use of antimicrobials in hospitals but not on how to improve it. University Hospital Virgen del Rocio (Seville) has launched the Institutional Programme for the Optimisation of Antimicrobial Treatment (PRIOAM), inspired by the recommendations of the Infectious Diseases Society of America and adapted to the structural, functional and cultural characteristics of the hospital. PRIOAM is coordinated by a multidisciplinary team chosen by the Committee on Infections and Antimicrobials and has three basic characteristics: it is an institutional programme that has incentives linked to achieving goals; it is an educational programme in which training and knowledge are the basis for the proper use of antimicrobials; and it is a programme subject to results, in which the main objectives are clinical, not economic, to reduce mortality and morbidity in patients with infections and to delay the development of resistance.

Atypical hemolytic uremic syndrome associated with Bordetella pertussis infection.

W have observed an increase in the incidence and severity of admissions for pertussis during recent years. Between 2007 and 2011 admissions per attending child to the emergency department increased by 993% (P = 0.002). Although no pediatric intensive care unit (ICU) admissions due to pertussis were recorded between 2007 and 2009, 11 infants needed ICU admission in 2010 to 2011, 2 of whom died. One of the remaining 9 infants developed hemolytic uremic syndrome (HUS) due to Bordetella pertussis infection, a very rare occurrence; her clinical characteristics are described in this report. A female infant was born at term via cesarean delivery due to intrapartum asphyxia. Birth weight was 4.120 kg. She was admitted to the neonatal ICU at 24 days of age for presumed respiratory syncytial virus–negative bronchiolitis as she had catarrhal symptoms and apneic episodes requiring nonmechanical ventilation. Fortyeight hours after transfer to the pediatric infectious disease ward on day 5, she developed severe and progressive respiratory distress accompanied by frequent apneic spells. She was readmitted to the ICU for mechanical ventilation. Polymerase chain reaction targeting IS481of B. pertussis was positive, and the infant received therapy with a 5-day course of azithromycin (10 mg/kg/d). The infant deteriorated clinically on day 17; blood analysis revealed microangiopathic hemolytic anemia (hemoglobin 5.2g/dL, reticulocytes 14.6%, schistocytes 5.3%, haptoglobin 5.3 mg/dL and lactate dehydrogenase 2642 UI/L), thrombocytopenia (65000/mm), prolonged coagulation profile (prothrombin time 15.6 seg, partial thromboplastin time noncoagulating, fibrinogen 0.7 mg/L) and renal impairment with rising creatinine values in 24 hours from 0.19 mg/dL to 0.62 mg/dL, marked proteinuria (178 mg/m/h) and bilateral renal hyperechogenicity on ultrasound examination. Atypical HUS (aHUS) was diagnosed, and management was supportive including infusions of fresh frozen plasma resulting in good clinical and laboratory response within a week, avoiding the need of dialysis. Genetic studies including complement factor H and I, as well as membrane cofactor protein (MCP) and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 were negative. However, the infant was homozygous for the MCP ggaac risk haplotype, and this may have increased her susceptibility to aHUS. Functional analysis of alternative complement pathway, including MCP expression on leukocytes, was normal. aHUS secondary to pertussis has been previously described in 5 cases. An additional patient had microangiopathic hemolytic anemia due to B. pertussis infection without renal involvement. All patients were < 6 weeks of age at diagnosis. Clinical symptoms of HUS occurred late in all patients, including ours, ranging between 6 and 42 days posthospital admission. All but 1 patient who had a fatal outcome made a full clinical recovery without renal sequel. The development of aHUS is determined by genetic predisposition and environmental factors including infections. Virulence factors of B. pertussis, such as pertussis toxin, filamentous hemaglutinin, fimbriae, pertactin, tracheal cytotoxin, adenylate cyclase as well as endotoxins, induce proinflammatory and procoagulation immune responses with subsequent endothelium damage and can induce aHUS. Genetic mutations and/or poly morphisms are known to play a role in the susceptibility and severity of HUS. One infant who died of pertussis and subsequent HUS suffered from complement factor H deficiency, and an MCP risk haplotype was identified in our patient. In summary B. pertussis infection can result in unusual but potentially fatal HUS, particularly in patients with predisposing genetic susceptibility. Acknowledgments: The authors thank Margarita Lopez Trascasa for performing complement regulatory factors genetic testing.

Long-Term Impact of an Educational Antimicrobial Stewardship Program on Hospital-Acquired Candidemia and Multidrug-Resistant Bloodstream Infections: A Quasi-Experimental Study of Interrupted Time-Series Analysis

Background The global crisis of bacterial resistance urges the scientific community to implement intervention programs in healthcare facilities to promote an appropriate use of antibiotics. However, the clinical benefits or the impact on resistance of these interventions has not been definitively proved. Methods We designed a quasi-experimental intervention study with an interrupted time-series analysis. A multidisciplinary team conducted a multifaceted educational intervention in our tertiary-care hospital over a 5-year period. The main activity of the program consisted of peer-to-peer educational interviews between counselors and prescribers from all departments to reinforce the principles of the proper use of antibiotics. We assessed antibiotic consumption, incidence density of Candida and multidrug-resistant (MDR) bacteria bloodstream infections (BSIs) and their crude death rate per 1000 occupied bed days (OBDs). Results A quick and intense reduction in antibiotic consumption occurred 6 months after the implementation of the intervention (change in level, -216.8 defined daily doses per 1000 OBDs; 95% confidence interval, -347.5 to -86.1), and was sustained during subsequent years (average reduction, -19,9%). In addition, the increasing trend observed in the preintervention period for the incidence density of candidemia and MDR BSI (+0.018 cases per 1000 OBDs per quarter; 95% confidence interval, -.003 to .039) reverted toward a decreasing trend of -0.130 per quarter (change in slope, -0.029; -.051 to -.008), and so did the mortality rate (change in slope, -0.015; -.021 to -.008). Conclusions This education-based antimicrobial stewardship program was effective in decreasing the incidence and mortality rate of hospital-acquired candidemia and MDR BSI through sustained reduction in antibiotic use.

Epidemiología de la colonización nasofaríngea por Streptococcus pneumoniae en niños menores de 6 años de la ciudad de Sevilla

INTRODUCTION The aim of this investigation was to study the epidemiology of nasopharyngeal (NP) colonization with Streptococcus pneumoniae after the introduction of the heptavalent pneumococcal conjugate vaccine (PCV7). METHODS NP swabs were obtained from 848 children aged 6 months to six years seen in four primary care centres (healthy children) and in two emergency depeartments (sick children) from Seville. The study was conducted between February 2005 and June 2008. RESULTS A total of 278 (33%) children carried S. pneumoniae. Pneumococcal colonization was independently predicted by school attendance or child care participation (OR 2.21; 95% CI 1.54- 3.15; P=.0001) and younger age. Recent antibiotic use was protective (OR 0.68; 95% CI 0.48-0.94; P=.02). PCV7 uptake was 41%. Risk of carriage of PCV7- type pneumococci was lower among children who had received ≥1 dose of PCV7 (7% vs 29%; [OR 0.21; 95% CI 0.09-0.49; P=.0001]). The proportion of pneumococcal isolates with oral penicillin non-susceptibility and amoxicillin resistance were 33% and 3%, respectively. Amoxicillin resistance in colonized children was associated with prior antibiotic usage (OR 4.29; 95% CI 1.09-20.02). CONCLUSIONS NP colonization rates with PCV7- type pneumococci were low compared to those found in studies prior to PCV7 introduction, both in vaccinated and unvaccinated subjects. Factors related to age and overcrowding increased the prevalence of pneumococcal carriage. Use of antibiotics reduced the overall carriage of pneumococci, but was a risk factor for colonization with amoxicillin resistant pneumococci.