Cyanotic congenital heart disease CCHD

Cyanotic congenital heart disease (CCHD) is an important predisposing factor for brain abscess formation in children, and accounts for 6–50% of cases in published series. The highest incidence of this complication appears to be among children with cardiac defects, such as tetralogy of Fallot or transposition of the great vessels; however, any condition resulting in a significant right-to-left shunt appears to increase the risk. Decreased oxygen saturation and increased blood viscosity may cause focal areas of brain ischemia that serve as nidi of infection. In a pediatric series of cerebral abscesses in patients with CCHD, A. aphrophilus was identified as the second most frequent infecting organism.
Clinical isolates of A. aphrophilus have been demonstrated to be susceptible to penicillin, ampicillin, and cephalosporins. However, a clinical failure with cefotaxime has been reported in a case of a β-lactamase negative strain. Ciprofloxacin and the newer fluoroquinolones have potent activity against A. aphrophilus, and can be used as alternatives for penicillin allergic individuals, and for those infected with strains resistant to cephalosporins. The present strain was susceptible to all hsp90 inhibitor tested according to the guidelines of the Clinical and Laboratory Standards Institute. We elected to use high-dose meropenem due to the track record of this antibiotic that has excellent central nervous system penetration in the treatment of brain abscesses.
If the condition is promptly diagnosed and appropriately treated, brain abscess mortality is low in patients with no predisposing conditions. By contrast, it is high (30–40%) in those with CCHD. A review of the English language medical literature since 1964 showed only 14 previously reported pediatric cases of brain abscess due to A. aphrophilus (Table 1). Eight (53%) of the 15 patients (including the present case) were males. Associated conditions were congenital heart disease in five cases, otitis media in three, dental procedures in two, and sinusitis in one case. No obvious source of infection was identified in the remaining four patients. Treatment consisted of surgical drainage combined with antimicrobial therapy in 13 (87%) cases. The overall mortality rate was 20%. One of the patients who died had underlying congenital heart disease, pulmonary hypertension and multiple brain abscesses, whereas the others were treated with surgery or antibiotics alone.
In conclusion, A. aphrophilus should be considered in the differential diagnosis of brain abscesses in children. Dental procedures, close contact with dogs, and CCHD are predisposing conditions. Prompt surgical drainage and prolonged antibiotic treatment are necessary to achieve a favorable clinical outcome.

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Acknowledgments

Introduction
Escherichia coli is the most common cause of Gram-negative bacteremia. For many years, a β-lactam in combination with an aminoglycoside has been the standard therapy for empirical therapy suspected or confirmed Gram-negative bacteremia. Depending on the prevalence of resistance, the preferred aminoglycoside in most geographic areas is either gentamicin or amikacin. Genes encoding aminoglycoside-modifying enzymes (AME) and 16S ribosomal RNA (rRNA) methylases are the main causes of aminoglycoside resistance. In Gram-negative bacteria, the main gentamicin-resistant, AME genes are aac(3′)-I, aac(3′)-II, aac(3′)-III, aac(4′)-IV, and ant(2′′)-I. Early epidemiological studies have shown that amikacin resistance often involved aac(6′)-Ib and occasionally aph(4′)-II and aph(3′)-VI. Because not all the substrates for a given AME may be tested resistant at the currently adopted breakpoints, interpretive reporting of susceptibility results is widely practiced according to the resistance profile of different aminoglycosides. Recent studies have also highlighted the increasing occurrence of 16S rRNA methylases, which cause high-level resistance [minimum inhibitory concentration (MIC) ≥ 512 μg/mL] to all the 4-,6-aminoglycosides. Therefore, there is a need to regularly update the prevalent aminoglycoside resistance mechanisms. Here, we investigated the occurrence and distribution of the major AME and 16S rRNA methylases in aminoglycoside-resistant E. coli.