Michael Dul

Carbapenem-resistant Acinetobacter baumannii and Klebsiella pneumoniae across a hospital system: impact of post-acute care facilities on dissemination

BACKGROUND Resistance to carbapenems among Acinetobacter baumannii and Klebsiella pneumoniae presents a serious therapeutic and infection control challenge. We describe the epidemiology and genetic basis of carbapenem resistance in A. baumannii and K. pneumoniae in a six-hospital healthcare system in Northeast Ohio. METHODS Clinical isolates of A. baumannii and K. pneumoniae distributed across the healthcare system were collected from April 2007 to April 2008. Antimicrobial susceptibility testing was performed followed by molecular analysis of carbapenemase genes. Genetic relatedness of isolates was established with repetitive sequence-based PCR (rep-PCR), multilocus PCR followed by electrospray ionization mass spectrometry (PCR/ESI-MS) and PFGE. Clinical characteristics and outcomes of patients were reviewed. RESULTS Among 39 isolates of A. baumannii, two predominant genotypes related to European clone II were found. Eighteen isolates contained bla(OXA-23), and four isolates possessed bla(OXA-24/40). Among 29 K. pneumoniae isolates with decreased susceptibility to carbapenems, two distinct genotypes containing bla(KPC-2) or bla(KPC-3) were found. Patients with carbapenem-resistant A. baumannii and K. pneumoniae were elderly, possessed multiple co-morbidities, were frequently admitted from and discharged to post-acute care facilities, and experienced prolonged hospital stays (up to 25 days) with a high mortality rate (up to 35%). CONCLUSION In this outbreak of carbapenem-resistant A. baumannii and K. pneumoniae across a healthcare system, we illustrate the important role post-acute care facilities play in the dissemination of multidrug-resistant phenotypes.

Clinical and molecular epidemiology of community-acquired methicillin-resistant Staphylococcus aureus infections among children with risk factors for health care-associated infection: 2001-2003.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) has recently emerged as a common cause of infection in children in many parts of the world. The epidemiology of community-acquired MRSA (CA-MRSA) among healthy children has been recently described. However, little is known about CA-MRSA in children with underlying medical conditions. Objective: To compare the clinical and molecular epidemiology of CA-MRSA in children with and without risk factors for health care-associated infections (RF-HAI). Methods: We conducted a 3-year retrospective cohort study of children with CA-MRSA infection. RF-HAI, including hospitalization within the past year, indwelling medical devices or chronic medical condition, were identified by chart review. Genetic relatedness of CA-MRSA strains was assessed by pulsed field gel electrophoresis. Polymerase chain reaction was used to detect Panton-Valentine leukocidin and determine staphylococcal chromosomal cassette carrying the mecA methicillin-resistant gene (SCCmec) type. Results: We identified 446 episodes of community-acquired S. aureus infections, of which 134 (30%) were caused by MRSA. During the 3-year study period, the proportion of S. aureus infections caused by MRSA rose from 15% (12 of 80) to 40% (93 of 235) (P < 0.001) with the increase noted predominately in children with skin and soft tissue infections. RF-HAI were identified in 56 (42%) patients with CA-MRSA. Among subjects with CA-MRSA, children with RF-HAI were more likely to have had an invasive infection than healthy children (32% versus 5%; P < 0.001). CA-MRSA isolates from children with RF-HAI were similar to those without RF-HAI; all laboratory-retained CA-MRSA isolates harbored the SCCmec type IV cassette, and almost all isolates were susceptible to trimethoprim-sulfamethoxazole and clindamycin. However, pulsed field gel electrophoresis revealed greater molecular diversity among CA-MRSA isolates recovered from children with RF-HAI compared with those from otherwise healthy children (P = 0.001). Additionally CA-MRSA isolates from children with RF-HAI were less likely to contain sequences for Panton-Valentine leukocidin (P < 0.001) and more likely to be resistant to 3 or more classes of antibiotics (P = 0.033). Conclusion: CA-MRSA strains recovered from children with RF-HAI were phenotypically similar to those recovered from healthy children The absence of SCCmec type II or III MRSA among children with RF-HAI suggests that CA-MRSA strains might have become endemic within pediatric health care facilities.

Risk factors and outcomes associated with severe Clostridium difficile infection in children

Background: The incidence and severity of Clostridium difficile infection (CDI) is increasing among adults; however, little is known about the epidemiology of CDI among children. Methods: We conducted a nested case-control study to identify the risk factors for and a prospective cohort study to determine the outcomes associated with severe CDI at 2 childrens hospitals. Severe CDI was defined as CDI and at least 1 complication or ≥2 laboratory or clinical indicators consistent with severe disease. Studied outcomes included relapse, treatment failure, and CDI-related complications. Isolates were tested to determine North American pulsed-field gel electrophoresis type 1 lineage. Results: We analyzed 82 patients with CDI, of whom 48 had severe disease. Median age in years was 5.93 (1.78–12.16) and 1.83 (0.67–8.1) in subjects with severe and nonsevere CDI, respectively (P = 0.012). All patients with malignancy and CDI had severe disease. Nine subjects (11%) had North American pulsed-field gel electrophoresis type 1 isolates. Risk factors for severe disease included age (adjusted odds ratio [95% confidence interval]: 1.12 [1.02, 1.24]) and receipt of 3 antibiotic classes in the 30 days before infection (3.95 [1.19, 13.11]). If infants less than 1 year of age were excluded, only receipt of 3 antibiotic classes remained significantly associated with severe disease. Neither the rate of relapse nor treatment failure differed significantly between patients with severe and nonsevere CDI. There was 1 death. Conclusions: Increasing age and exposure to multiple antibiotic classes were risk factors for severe CDI. Although most patients studied had severe disease, complications were infrequent. Relapse rates were similar to those reported in adults.

Presence of the epidemic North American Pulsed Field type 1 Clostridium difficile strain in hospitalized children.

A hypervirulent strain of Clostridium difficile-labeled North American Pulsed Field type 1 causes severe disease in adults. To determine the prevalence of NAP1 C. difficile in children, organisms from consecutive C. difficile toxin-positive stool samples at 2 childrens hospitals microbiology laboratories were characterized. We found that 19.4% of these samples were NAP1.

Serogroup 19 Pneumococci Containing Both mef and erm Macrolide Resistance Determinants in an American City

Background: Asia has experienced a striking incidence of infection by highly resistant pneumococi containing both principal macrolide resistance determinants, namely, the mef efflux pump and the erm ribosomal methylase. mef/erm-containing pneumococci have not been identified in significant numbers in North America. Methods: Pneumococci were isolated as part of a larger study in Cleveland, OH examining colonization patterns among children randomized to 1 of 4 outpatient antibiotics for acute otitis media. Azithromycin-resistant organisms were tested for the presence of mef and erm sequences by polymerase chain reaction. The clonal relationship of pneumococci containing both genes was determined by pulsed field gel electrophoresis and multilocus sequence testing. Selected characteristics of children harboring mef/erm-containing organisms were compared with other participants of the larger study. Results: Of 221 children colonized by pneumococci, 17 (7.7%) were colonized with an organism containing both determinants. All mef/erm-positive organisms demonstrated azithromycin minimum inhibitory concentrations ≥256 &mgr;g/mL and were coresistant to all other agents tested. The mef/erm-containing organisms were serotype 19A and 19F, all but 1 of which manifested similar pulsed field gel electrophoresis patterns. Multilocus sequence testing analysis indicated a relationship to the Taiwan19F-14 macrolide-resistant strain that has spread throughout Eastern Asia. More than one-third of children colonized by a mef/erm-containing organism had received ≥1 dose of conjugate pneumococcal vaccine, a significantly higher proportion than children carrying less resistant organisms (P< 0.01). No other characteristics distinguished children harboring a mef/erm-containing pneumococcus from other children enrolled in the larger study. Conclusion: Clonally related mef/erm-containing serogroup 19 pneumococci were prominent among otherwise healthy children in a North American metropolitan area. Our findings suggest that spread of these organisms may be poorly contained by immunization.

Impact of amoxicillin on pneumococcal colonization compared with other therapies for acute otitis media.

Background: This study compared the effects of 4 outpatient antibiotic regimens on colonization by penicillin-susceptible and -nonsusceptible pneumococci to assess their relative potential to promote colonization with Streptococcus pneumoniae with reduced susceptibility to penicillin. Methods: Children presenting with acute otitis media were randomized to receive amoxicillin, cefprozil, ceftriaxone or azithromycin. Nasopharyngeal specimens were collected on days 0, 3–5, 10–14 and 28–30 and assessed for the presence of S. pneumoniae. At each visit, the proportions of penicillin-susceptible and -nonsusceptible pneumococci were compared among treatment groups. Results: Among 1009 enrollees, the prevalence of colonization by S. pneumoniae at baseline was 23.5%, of which 41.1% were penicillin-nonsusceptible. Colonization by nonsusceptible pneumococci was unaltered during the observation period in all treatment groups, with no detectable differences among groups at each visit. By contrast, there was a substantial reduction in the prevalence of colonization by penicillin-susceptible organisms, most notably in subjects treated with amoxicillin. This resulted in a proportional shift toward resistant organism colonization in all groups, with this shift being significantly more pronounced among amoxicillin recipients than in the other groups at 10–12 days (P < 0.02 for each comparison with amoxicillin). Conclusions: Treatment with amoxicillin for acute otitis media resulted in a larger shift toward nonsusceptible organism colonization among those children still colonized postexposure than did treatment with 3 comparison agents. This phenomenon raises theoretical concerns that at the population level, amoxicillin produces conditions that promote the dissemination of the nonsusceptible phenotype more readily than other outpatient antibiotics. Confirmation of these results requires further study.

Meropenem use and colonization by antibiotic-resistant Gram-negative bacilli in a pediatric intensive care unit.

Objective: The carbapenems are broad-spectrum &bgr;-lactam antibiotics with activity against most organisms encountered in the pediatric intensive care unit (PICU). In anticipation of their increased use in critically ill children, we measured the effect of sustained meropenem use on the pattern of Gram-negative bacillus colonization in patients admitted to a tertiary care PICU. Design: Prospective preintervention/postintervention comparison. Setting: Medical/surgical PICU. Patients: Consecutive PICU admissions over 2.5 yrs. Interventions: After a 6-mo baseline period, all children with serious infections admitted to the PICU during the subsequent 2 yrs were administered meropenem. The incidence of colonization by Gram-negative bacilli resistant to one of a battery of broad-spectrum parenteral agents, and by organisms resistant specifically to meropenem, during the baseline period was compared with the period of preferred meropenem use. Results: During the period of preferred meropenem use, the amount of meropenem used increased >seven-fold, whereas the use of other advanced generation &bgr;-lactams was reduced by nearly 80%. The mean prevalence of colonization by antibiotic-resistant bacilli in general was not statistically altered during the period of meropenem preference (7.3 organisms/100 patient-days, vs. 9.4 organisms/100 patient-days at baseline, p < 0.09). The prevalence of colonization by Gram-negative organisms resistant specifically to meropenem was 0.61 organisms/100 patient-days during the baseline period vs. 1.04 organisms/100 patient-days during the period of meropenem preference (p < 0.30). The incidence of nosocomial infections did not change, and the prevalence of nosocomial infections caused by meropenem-resistant organisms was always <1% of all admissions during the period of meropenem preference. Conclusion: There was no statistically detectable effect on the prevalence of colonization by Gram-negative organisms resistant to one or more classes of broad-spectrum parenteral antibiotics, or to colonization by organisms resistant specifically to meropenem, when meropenem was the preferred antibiotic in a PICU.

Comparative effects of single-dose ceftriaxone versus three oral antibiotic regimens on stool colonization by resistant bacilli in children.

Objective: The use of short-term intramuscular ceftriaxone for pediatric ambulatory conditions raises concerns regarding the promotion of resistance among colonizing enteric bacteria. This study was designed to assess the prevalence of stool colonization with resistant Gram-negative bacilli after single-dose ceftriaxone treatment compared with other regimens for acute otitis media. Methods: Children age 3 months to 7 years and diagnosed with acute otitis media were randomized to receive treatment with single-dose ceftriaxone or with oral cefprozil, amoxicillin or azithromycin. Stool samples were obtained at enrollment and then 3–5 days, 10–14 days, and 28–30 days after therapy was initiated and screened for the presence of facultative Gram-negative bacilli resistant to ceftriaxone, cefprozil, amoxicillin, piperacillin, piperacillin-tazobactam and tobramycin. Mean prevalence of colonization by resistant organisms for each treatment group was compared at each time point. Results: One thousand nine subjects were enrolled. The prevalence of colonization by a Gram-negative bacillus resistant to at least 1 of the screening antibiotics decreased after receipt of ceftriaxone but returned close to values measured at study entry by 30 days. A qualitatively similar pattern was noted for the 3 other regimens, but a quantitatively greater decrease in the prevalence of colonization by a resistant bacterium was noted at the 3- to 5-day and 10- to 14-day visits among azithromycin recipients (P < 0.001). Colonization by a Gram-negative bacillus resistant specifically to ceftriaxone was unusual at each study visit, regardless of treatment assignment. Conclusions: A single intramuscular dose of ceftriaxone had a similar effect on the prevalence of antibiotic-resistant Gram-negative facultative bacilli in the stool of healthy children when compared with commonly used oral agents.

Change in pneumococcal susceptibility to azithromycin during treatment for acute otitis media.

Authorities have suggested restriction of azithromycin use as a principal strategy to contain the spread of azithromycin-nonsusceptible Streptococcus pneumoniae (ANSP). In 83 children persistently colonized by pneumococcus during and after treatment of acute otitis media, 17 acquired a new strain, 9 of which were less susceptible to azithromycin than the original isolate. New appearance of ANSP was documented after both β-lactam and azithromycin exposure. ANSP is likely to disseminate even with significant reduction of azithromycin use unless other antibiotic use is decreased as well.