Emergence of domestically acquired ceftriaxone-resistant Salmonella infections associated with AmpC beta-lactamase

Context  Ceftriaxone, an expanded-spectrum cephalosporin, is an antimicrobial agent commonly used to treat severe Salmonella infections, especially in children. Ceftriaxone-resistant Salmonella infections have recently been reported in the United States, but the extent of the problem is unknown. Objectives  To summarize national surveillance data for ceftriaxone-resistant Salmonella infections in the United States and to describe mechanisms of resistance. Design and Setting  Case series and laboratory evaluation of human isolates submitted to the Centers for Disease Control and Prevention from 17 state and community health departments participating in the National Antimicrobial Resistance Monitoring System (NARMS) for enteric bacteria between 1996 and 1998. Patients  Patients with ceftriaxone-resistant Salmonella infections between 1996 and 1998 were interviewed and isolates with decreased ceftriaxone susceptibility were further characterized. Main Outcome Measures  Exposures and illness outcomes, mechanisms of resistance. Results  The prevalence of ceftriaxone-resistant Salmonella was 0.1% (1 of 1326) in 1996, 0.4% (5 of 1301) in 1997, and 0.5% (7 of 1466) in 1998. Ten (77%) of the 13 patients with ceftriaxone-resistant infections were aged 18 years or younger. The patients lived in 8 states (California, Colorado, Kansas, Massachusetts, Maryland, Minnesota, New York, and Oregon). Nine (82%) of 11 patients interviewed did not take antimicrobial agents and 10 (91%) did not travel outside the United States before illness onset. Twelve of the 15 Salmonella isolates with ceftriaxone minimum inhibitory concentrations of 16 µg/mL or higher were serotype Typhimurium but these isolates had different pulsed-field gel electrophoresis patterns. Thirteen of these 15 isolates collected between 1996 and 1998 were positive for a 631–base pair polymerase chain reaction product obtained by using primers specific for the ampC gene of Citrobacter freundii. Conclusions  Domestically acquired ceftriaxone-resistant Salmonella has emerged in the United States. Most ceftriaxone-resistant Salmonella isolates had similar AmpC plasmid-mediated resistance.      

Otoacoustic emissions as a screening test for hearing impairment in children recovering from acute bacterial meningitis

OBJECTIVES: To study the efficacy of otoacoustic emissions (OAEs) as a screening test for hearing impairment in children with acute bacterial meningitis. Hearing tests were performed before discharge from the hospital in an attempt to improve coverage and avoid delays in the diagnosis of postmeningitic hearing loss. METHODS: Children with bacterial meningitis were recruited from 21 centers. In the 48 hours before discharge from the hospital, all patients underwent a thorough audiologic assessment consisting of transient evoked OAEs, auditory brainstem responses (ABRs), otoscopy, and tympanometry. Hearing loss was defined as ABR threshold >/=30 dB. The results of OAE screening were compared with the gold standard of ABR threshold. RESULTS: Of 124 children recruited, we were able to perform both OAEs and ABRs on 110 children. Seven (6.3%) of the 110 children had ABR threshold >/=30 dB; 2 had sensorineural hearing loss and 5 had conductive hearing loss. At follow-up, hearing loss persisted in both cases of sensorineural hearing loss and no new cases were identified. All 7 children with hearing loss failed the OAE screening test. Ninety-four children with normal hearing thresholds passed the test, and 9 failed. Thus, the screening test had a sensitivity of 1.00 (95% confidence interval, 0.59 to 1.00), a specificity of 0.91 (0.85 to 0.97), a positive predictive value of 0. 44 (0.20 to 0.70), and a negative predictive value of 1.00 (0.96 to 1.00). CONCLUSIONS: OAE screening in children recovering from meningitis was found to be feasible and effective. The test was highly sensitive and reasonably specific. Inpatient OAE screening should allow early diagnosis of postmeningitic hearing loss and prompt auditory rehabilitation.     

Iron-induced oxidative DNA damage and its repair in primary rat hepatocyte culture

Iron-overload diseases frequently develop hepatocellular carcinoma. The genotoxic mechanism whereby iron is involved in hepatocarcinogenesis might involve an oxidative process via the intermediate production of reactive oxygen species. This was presently investigated by examining kinetics of formation and repair of DNA base lesions in primary rat hepatocyte cultures supplemented with the iron chelate, ferric nitrilotriacetate Fe-NTA (10 and 100 microM). Seven DNA base oxidation products have been identified in DNA extracts by gas chromatography- mass spectrometry, which showed a predominance of oxidized-purines (8- oxo-guanine, xanthine, fapy-adenine, 2-oxo-adenine) above oxidized pyrimidines (5-OHMe-uracil, 5-OH-uracil, 5-OH-cytosine) in control cultures. All these DNA oxidation products revealed a significant dose- dependent increase at 4 to 48 h after Fe-NTA supplementation, among which fapy-adenine showed the highest increase and 5-OH-cytosine was the least prominent. Involvement of iron in this oxidative process was established by a correlation between extent in DNA oxidation and intracellular level of toxic low molecular weight iron. DNA excision- repair activity was estimated by release of DNA oxidation products in culture medium. All the seven DNA oxidation products were detected in the medium of control cultures and showed basal repair activity. This DNA repair activity was increased in a time- and dose-dependent fashion with Fe-NTA. Oxidized-pyrimidines, among which was 5-OHMe-Uracil, were preferentially repaired, which explains the low levels detected in oxidized DNA. Since oxidized bases substantially differed from one another in terms of excision rates from cellular DNA, specific excision- repair enzymes might be involved. Our findings, however, demonstrate that even though DNA repair pathways were activated in iron-loaded hepatocyte cultures, these processes were not stimulated enough to prevent an accumulation of highly mutagenic DNA oxidative products in genomic DNA. The resulting genotoxic effect of Fe-NTA might be relevant in understanding the hepatocarcinogenic evolution of iron-overload diseases.      

Eradication of methicillin-resistant Staphylococcus aureus from a neonatal intensive care unit by active surveillance and aggressive infection control measures.

OBJECTIVES: To describe an outbreak of hospital-acquired MRSA in a NICU and to identify the risk factors for, outcomes of, and interventions that eliminated it. SETTING: An 18-bed, level III-IV NICU in a community hospital. METHODS: Interventions to control MRSA included active surveillance, aggressive contact isolation, and cohorting and de-colonization of infants and HCWs with MRSA. A case-control study was performed to compare infants with and without MRSA. RESULTS: A cluster of 6 cases of MRSA infection between September and October 2001 represented an increased attack rate of 21.2% compared with 5.3% in the previous months. Active surveillance identified unsuspected MRSA colonization in 6 (21.4%) of 28 patients and 6 (5.5%) of 110 HCWs screened. They were all successfully decolonized. There was an increased risk of MRSA colonization and infection among infants with low birth weight or younger gestational age. Multiple gestation was associated with an increased risk of colonization (OR, 37.5; CI95, 3.9-363.1) and infection (OR, 5.36; CI95, 1.37-20.96). Gavage feeding (OR, 10.33; CI95, 1.28-83.37) and intubation (OR, 5.97; CI95, 1.22-29.31) were associated with increased risk of infection. Infants with MRSA infection had a significantly longer hospital stay than infants without MRSA (51.83 vs 21.46 days; P = .003). Rep-PCR with mec typing and PVL analysis confirmed the presence of a single common strain of hospital-acquired MRSA. CONCLUSION: Active surveillance, aggressive implementation of contact isolation, cohorting, and decolonization effectively eradicated MRSA from the NICU for 2 1/2 years following the outbreak.     

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European Journal of Clinical Microbiology & Infectious Diseases -     

A randomized controlled trial testing the effectiveness of a universal school-based depression prevention program 'Op Volle Kracht' in the Netherlands

Background  

The incidence of depressive symptoms increases during adolescence, from 10.0% to 24.5% at age 11 to 15, respectively. Experiencing elevated levels of depressive symptoms increases the risk of a depressive disorder in adulthood. A universal school-based depression prevention program Op Volle Kracht (OVK) was developed, based on the Penn Resiliency Program, aimed at preventing the increase of depressive symptoms during adolescence and enhancing positive development. In this study the effectiveness of OVK will be tested and possible mediators of program effects will be focus of study as well.