Multidrug and Mupirocin Resistance in Environmental Methicillin-Resistant Staphylococcus aureus (MRSA) Isolates from Homes of People Diagnosed with Community-Onset MRSA Infection.

Patients with community-onset (CO) methicillin-resistant Staphylococcus aureus (MRSA) infections contribute to MRSA contamination of the home environment and may be reexposed to MRSA strains from this reservoir. This study evaluates One Health risk factors, which focus on the relationship between humans, animals, and the environment, for the increased prevalence of multiple antimicrobial-resistant MRSA isolates in the home environment. During a trial of patients with CO-MRSA infection, MRSA was isolated from the household environment at the baseline and 3 months later, following randomization of patients and household members to mupirocin-based decolonization therapy or an education control group. Up to two environmental MRSA isolates collected at each visit were tested. MRSA isolates were identified in 68% (65/95) of homes at the baseline (n = 104 isolates) and 51% (33/65) of homes 3 months later (n = 56 isolates). The rates of multidrug resistance (MDR) were 61% among isolates collected at the baseline and 55% among isolates collected at the visit 3 months later. At the baseline, 100% (14/14) of MRSA isolates from rural homes were MDR. While antimicrobial use by humans or pets was associated with an increased risk for the isolation of MDR MRSA from the environment, clindamycin use was not associated with an increased risk for the isolation of MDR MRSA. Incident low-level mupirocin-resistant MRSA strains were isolated at 3 months from 2 (5%) of 39 homes that were randomized to mupirocin treatment but none of the control homes. Among patients recently treated for a CO-MRSA infection, MRSA and MDR MRSA were common contaminants in the home environment. This study contributes to evidence that occupant use of antimicrobial drugs, except for clindamycin, is associated with MDR MRSA in the home environmental reservoir. (This study has been registered at ClinicalTrials.gov under registration no. NCT00966446.)IMPORTANCE MRSA is a common bacterial agent implicated in skin and soft tissue infections (SSTIs) in both community and health care settings. Patients with CO-MRSA infections contribute to environmental MRSA contamination in these settings and may be reexposed to MRSA strains from these reservoirs. People interact with natural and built environments; therefore, understanding the relationships between humans and animals as well as the characteristics of environmental reservoirs is important to advance strategies to combat antimicrobial resistance. Household interactions may influence the frequency and duration of exposure, which in turn may impact the duration of MRSA colonization or the probability for recurrent colonization and infection. Therefore, MRSA contamination of the home environment may contribute to human and animal recolonization and decolonization treatment failure. The aim of this study was to evaluate One Health risk factors that may be amenable to intervention and may influence the recovery of MDR and mupirocin resistance in CO-MRSA isolates.

Factors associated with persistent colonisation with methicillin-resistant Staphylococcus aureus.

We conducted a prospective cohort study between 1 January 2010 and 31 December 2012 at five adult and paediatric academic medical centres to identify factors associated with persistent methicillin-resistant Staphylococcus aureus (MRSA) colonisation. Adults and children presenting to ambulatory settings with a MRSA skin and soft tissue infection (i.e. index cases), along with household members, performed self-sampling for MRSA colonisation every 2 weeks for 6 months. Clearance of colonisation was defined as two consecutive negative sampling periods. Subjects without clearance by the end of the study were considered persistently colonised and compared with those who cleared colonisation. Of 243 index cases, 48 (19·8%) had persistent colonisation and 110 (45·3%) cleared colonisation without recurrence. Persistent colonisation was associated with white race (odds ratio (OR), 4·90; 95% confidence interval (CI), 1·38-17·40), prior MRSA infection (OR 3·59; 95% CI 1·05-12·35), colonisation of multiple sites (OR 32·7; 95% CI 6·7-159·3). Conversely, subjects with persistent colonisation were less likely to have been treated with clindamycin (OR 0·28; 95% CI 0·08-0·99). Colonisation at multiple sites is a risk factor for persistent colonisation and may require more targeted decolonisation efforts. The specific effect of clindamycin on MRSA colonisation needs to be elucidated.

The impact of household transmission on duration of outpatient colonization with methicillin-resistant Staphylococcus aureus.

We identified eight consecutive patients who presented with a skin or soft tissue infection due to MRSA. Of seven household members of these cases, three were colonized with MRSA. The mean duration of MRSA colonization in index cases was 33 days (range 14-104), while mean duration of colonization in household cases was 54 days (range 12-95). There was a borderline significant association between having a concurrent colonized household member and a longer duration of colonization (mean 44 days vs. 26 days, P=0.08).

The potential economic value of sputum culture use in patients with community-acquired pneumonia and healthcare-associated pneumonia.

OBJECTIVE: Despite numerous studies, the clinical value of sputum cultures in the management of pneumonia remains controversial; therefore, understanding the economic value of sputum cultures may help decision makers determine their appropriate use in patient management. METHODS: We developed a decision model to determine the economic and clinical value of using sputum cultures in the treatment of community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP) from the hospital perspective under various conditions. RESULTS: For both CAP and HCAP patients, obtaining sputum cultures resulted in similar costs compared to no culture, even if cultures cost $0. Given current clinical practices, obtaining cultures cost $539-631 more per CAP patient and $13-170 per HCAP patient compared to no culture use. However, cultures saved $8-202 per HCAP patient with a 40% probability the pathogen was the true cause (75% reduction in adverse outcomes, greater length of hospital stay (LOS) increase) to a 70% probability the pathogen was the true cause (25% reduction in outcomes and greater LOS increase and a 75% reduction in outcomes and all LOS increases). Additionally, obtaining sputum cultures had no impact on the number of adverse outcomes (i.e., adverse drug events, Clostridium difficile infection, pneumonia readmissions, additional hospitalization days). When all patients were treated with antibiotics empirically, obtaining cultures saved $4-342. CONCLUSIONS: Overall, obtaining sputum cultures does not provide significant clinical or economic benefits for CAP or HCAP patients; however, it can reduce costs and shorten overall LOS under some circumstances. Clinicians should consider their local conditions when making decisions about sputum culture use.

Gut microbiome alteration in MORDOR I: a community-randomized trial of mass azithromycin distribution.

The MORDOR I trial1, conducted in Niger, Malawi and Tanzania, demonstrated that mass azithromycin distribution to preschool children reduced childhood mortality1. However, the large but simple trial design precluded determination of the mechanisms involved. Here we examined the gut microbiome of preschool children from 30 Nigerien communities randomized to either biannual azithromycin or placebo. Gut microbiome γ-diversity was not significantly altered (P = 0.08), but the relative abundances of two Campylobacter species, along with another 33 gut bacteria, were significantly reduced in children treated with azithromycin at the 24-month follow-up. Metagenomic analysis revealed functional differences in gut bacteria between treatment groups. Resistome analysis showed an increase in macrolide resistance gene expression in gut microbiota in communities treated with azithromycin (P = 0.004). These results suggest that prolonged mass azithromycin distribution to reduce childhood mortality reduces certain gut bacteria, including known pathogens, while selecting for antibiotic resistance.

Motor nerve terminal degeneration provides a potential mechanism for rapid recovery in acute motor axonal neuropathy after Campylobacter infection.

We investigated the possible mechanisms of paralysis and recovery in a patient with the acute motor axonal neuropathy (AMAN) pattern of the Guillain-Barré syndrome. The AMAN pattern of GBS is characterized clinically by acute paralysis without sensory involvement and electrodiagnostically by low compound motor action potential amplitudes, suggesting axonal damage, without evidence of demyelination. Many AMAN patients have serologic or culture evidence of recent Campylobacter jejuni infection. Pathologically, the most severe cases are characterized by wallerian-like degeneration of motor axons affecting the ventral roots as well as peripheral nerves, but some fatal cases have only minor changes in the roots and peripheral nerves, and some paralyzed patients with the characteristic electrodiagnostic findings of AMAN recover rapidly. The mechanism of paralysis and recovery in such cases has been uncertain. A 64-year-old woman with culture-proven Campylobacter upsaliensis diarrhea developed typical features of AMAN. She improved quickly following plasmapheresis. Her serum contained IgG anti-GM1 antibodies. The lipopolysaccharide of the organism bound peanut agglutinin. This binding was blocked by cholera toxin, suggesting that the organism contained the Gal(beta1-3)GalNAc epitope of GM1 in its lipopolysaccharide. Motor-point biopsy showed denervated neuromuscular junctions and reduced fiber numbers in intramuscular nerves. In contrast, the sural nerve biopsy was normal and skin biopsy showed normal dermal and epidermal innervation. In AMAN the paralysis may reflect degeneration of motor nerve terminals and intramuscular axons. In addition, the anti-GM1 antibodies, which can bind at nodes of Ranvier, might produce failure of conduction. These processes are potentially reversible and likely to underlie the capacity for rapid recovery that characterizes some cases of AMAN.

Campylobacter jejuni lipopolysaccharides in Guillain-Barré syndrome: molecular mimicry and host susceptibility.

OBJECTIVE: This study was designed to determine if the presence of specific ganglioside-like moieties in Campylobacter lipopolysaccharides (LPSs) is related to the development of Guillain-Barré syndrome (GBS), and to discover how frequently such moieties, including GM1, are present in these LPSs. METHODS: We studied Campylobacter isolates and sera from seven patients with GBS (five acute motor axonal neuropathy, one acute inflammatory demyelinating polyneuropathy, and one Fisher's syndrome), and compared them with similar specimens from patients with Campylobacter enteritis alone. RESULTS: All GBS patients had antiganglioside antibodies. Anti-GM1 and anti-GD1a titers were significantly elevated in post-Campylobacter GBS, both axonal and demyelinating, compared with normal control subjects or those with uncomplicated Campylobacter diarrhea. Campylobacter isolated from patients with GBS and with enteritis alone had similar ganglioside-like moieties. CONCLUSIONS: These results indicate that patients who develop GBS respond differently to the ganglioside-like epitopes on Campylobacter than do non-GBS diarrhea patients. Our findings support a role for host susceptibility as a determinant for the outcome following Campylobacter infection. These findings have important implications for the development of vaccines against Campylobacter jejuni.

The clinical significance of streptococcal species isolated from cerebrospinal fluid.

Alpha-hemolytic (viridans) streptococci are often isolated from cerebrospinal fluid (CSF); however, the significance of such isolates is poorly understood. In order to clarify the clinical significance of isolating these organisms from CSF, we did a retrospective analysis of 43 patients, from whom eight different species of alpha-hemolytic streptococci were recovered. Eight patients (19%) had significant infections based on bacteriologic, laboratory, and clinical findings. Significant infections were associated with S. sanguis, S. salivarius, S. intermedius, S. faecalis, and S. bovis. Thirty-five patient isolates (81%) from CSF were considered as contaminants, with S. mitis being the most frequently isolated organism (49%). Direct gram stain of CSF sediment, CSF glucose concentration, and CSF cell differential were clearly abnormal in most patients with significant infections, in contrast to patients with streptococci isolated as contaminants. Cultures of the lumbar puncture skin site yielded streptococci and other bacteria, suggesting a possible reservoir for contaminants.

Direct wet mounts versus concentration for routine parasitological examination: are both necessary?

The authors evaluated the usefulness of direct wet mount microscopic examination of stool samples for routine parasitologic diagnosis compared with formalin-ethyl acetate concentration detection. Over a three-year period, there were no instances in which an intestinal parasite was detected only by the direct wet mount examination. Elimination of routine direct wet mount examinations can reduce laboratory cost and save significant technologist time without decreasing the sensitivity of microscopic examinations for common parasitic agents.

Detection of Neisseria gonorrhoeae in cervical swabs using the Gonozyme enzyme immunoassay. Clinical evaluation in a university family planning clinic.

The authors performed a prospective clinical evaluation of the Gonozyme (Abbott Laboratories, Chicago, IL) assay in a family planning clinic population. One thousand five hundred eighty-eight female patients were screened for gonococcal infection using culture and Gonozyme assay. One hundred nine patients were culture positive (6.9% disease prevalence). The sensitivity and specificity of the Gonozyme assay in this setting was 87.2% and 89.1%, respectively. The predictive value of a positive and negative test, given a disease prevalence of 6.9%, was 37.2% and 98.9%, respectively. The false-positive and false-negative rate was 10.9% and 12.8%, respectively. The authors prospectively followed patients with true-positive and false-positive Gonozyme results. The Gonozyme test showed a 83% correlation with test of cure cultures and, thus, should not be used for test cure analysis. False-positive Gonozyme tests could not be explained on the basis of cross-reacting bacteria or detection of vancomycin-sensitive gonococci. The authors' results suggest that the Gonozyme test should not be used in lieu of culture in a clinical setting with a similar population.

PIP: The authors performed a prospective, clinical evaluation of the Gonozyme assay in a family planning clinic population. 1588 female patients were screened for gonococcal infection using culture and Gonozyme assay. 109 patients were culture positive (6.9% disease prevalence). The sensitivity and specificity of the Gonozyme assay in this setting was 87.2% and 89.1% respectively. The predictive value of a positive and negative test, given a disease prevalence of 6.9%, was 37.2% and 98.9%, respectively. The false positive and false negative rate was 10.9% and 12.8% respectively. The authors prospectively followed patients with true positive and false positive Gonozyme results. The Gonozyme test showed an 83% correlation with test of cure cultures and, thus, should not be used for test of cure analysis. False positive Gonozyme tests could not be explained on the basis of cross-reacting bacteria or detection of vancomycin sensitive gonococci. Results suggest that the Gonozyme test should not be used in lieu of culture in a clinical setting with a similar population.

Chlamydial infections.

Chlamydiae are small bacteria that have a unique life cycle. There are two species, Chlamydia psittaci and C. trachomatis, which cause a wide spectrum of clinical disease, including neonatal conjunctivitis and pneumonia, sexually transmitted disease, psittacosis, and trachoma. The importance of chlamydial disease in public health is being increasingly recognized, and the incidence in developed countries seems to be increasing. An understanding of chlamydial disease, its prevention and treatment, is essential for the infection control practitioner, who can play a significant role in patient education.

Molecular mimicry in Guillain-Barré syndrome.

Guillain-Barré syndrome (GBS) is the commonest cause of acute flaccid paralysis worldwide. Recent pathological and electrodiagnostic studies indicated that there are different patterns within this syndrome. The demyelinating pattern predominates in North America and Europe, whereas axonal variants of GBS occur more frequently in Northern China. Infection with Campylobacter jejuni is one of the most frequently recognized antecedent events in all variants of GBS. The lipopolysaccharides of these organisms share ganglioside-like epitopes with peripheral nerves, and patients with GBS have antiganglioside antibodies. These observations have given rise to the hypothesis that "molecular mimicry" is the immunopathogenic mechanism of injury to peripheral nerve fibers. With this hypothesis in view, we summarize our experience of GBS as it occurs in Northern China. To explore the role of molecular mimicry in this cohort we sought evidence of preceding Campylobacter infection and correlated this with clinical characteristics and antiganglioside serology. Based on our results we propose a sequence of pathogenic events leading to peripheral nerve injury in GBS.

Prototheca zopfii isolated from a patient with olecranon bursitis.

Prototheca zopfii was isolated from a patient with olecranon bursitis. Olecranon bursitis caused by Prototheca is a distinct clinical entity. Recognition of this infection was made by observing characteristic organisms in tissue and subsequent isolation of the organism.

Performance of two rapid, single-use immunoassays for the detection of Clostridium difficile toxin A.

Two rapid, single-use immunoassays for C. difficile toxin A, the Clearview C. DIFF A (Wampole Laboratories, Cranbury, N.J.) and the ImmunoCard Toxin A assays (Meridian Diagnostics Inc., Cincinnati, Ohio) were compared to the cytotoxin assay for their ability to detect C. difficile toxin in fecal specimens. A total of 537 specimens were tested and 47 (8.8%) were positive by the cytotoxin assay. The sensitivity, specificity, positive predictive value, and negative predictive value of the toxin A assays were as follows: 70.2% (95% CI, 57.1 to 83.3), 98.8% (95% CI, 97.8 to 99.8), 84.6% (95% CI, 73.3 to 95.9), and 97.2% (95% CI, 95.7 to 98.6) respectively for the Clearview assay; and 74.5% (95% CI, 62.0 to 86.9), 99.0% (95% CI, 98.1 to 99.9), 87.5% (95% CI, 77.3 to 97.8), and 97.6% (95% CI, 96.2 to 98.9) respectively for the ImmunoCard assay. Both toxin A assays are less sensitive than the cytotoxin assay, however, these assays offer a rapid and easy-to-perform test that may be used in conjunction with the cytotoxin assay for laboratory confirmation of C. difficile-associated disease.

In vitro activity of amdinocillin in combination with other beta-lactam antibiotics against aminoglycoside-susceptible and resistant gram-negative bacteria.

Amdinocillin alone and in combination with other beta-lactam antibiotics was tested for in vitro activity against aminoglycoside-susceptible and resistant gram-negative bacteria. Amdinocillin alone or in combination with ampicillin, ticarcillin, piperacillin, cefazolin, cefoxitin, and cefamandole had little to no activity against aminoglycoside-resistant E. coli, E. cloacae, K. pneumoniae, and S. marcescens. There was better activity with aminoglycoside-susceptible organisms, however, Overall, there was significantly more antagonism of amdinocillin combinations when tested with aminoglycoside-resistant organisms than with aminoglycoside-susceptible strains.

Comparison of two selective media for the isolation of Campylobacter species from a pediatric population in Mexico.

Two selective media for the isolation of Campylobacter species, a blood containing medium (CampyBAP) and blood-free, charcoal based formulation (CCDA) were compared for the ability to isolate Campylobacter species during a 1-year period. Of the 1,132 stool samples cultured during the study, 42 Campylobacter species were recovered using both media (3.7% yield). CCDA was better than CampyBAP for isolating C. jejuni subsp jejuni (18/20 vs 8/20, P = 0.002) and for all isolates, CCDA was superior over CampyBAP (39/42 vs 13/42, P < 0.0001). Overall, CCDA is a superior medium compared with CampyBAP for isolating Campylobacter species in our study population.

Recurrent catheter-related Rhodotorula rubra infection.

A 34-year-old male receiving chronic parenteral nutrition for treatment of short bowel syndrome and intermittent immunosuppressive agents for juvenile rheumatoid arthritis developed recurrent, catheter-associated Rhodotorula rubra fungemia over a one-year period. Infection with this yeast is associated with insertion of central venous catheters. Recurrence of R. rubra infection is an unusual event that presumably occurred because of chronic skin colonization by the organism.

Lipopolysaccharide induces expression of genes encoding pro-inflammatory cytokines and the elastin-degrading enzyme, cathepsin S, in human cervical smooth-muscle cells.

OBJECTIVE: Vaginal and amniotic infection with gram-negative bacteria is associated with preterm birth. We previously reported that human cervical smooth-muscle cells (CSMC) respond to pro-inflammatory cytokines by expressing enzymes that degrade the extracellular matrix. Our objective was to characterize the effects of lipopolysaccharide (LPS) from Escherichia coli (E coli), Bacteroides fragilis, (B frag)and Fusobacterium nucleatum (F nuc)on the expression of pro-inflammatory cytokines and the elastin-degrading enzyme, cathepsin S, in human CSMC. METHODS: Human CSMC were exposed to LPS and the expression of mRNAs encoding pro-inflammatory cytokines and cathepsin S, and selected matrix metalloproteinases (MMPs) was analyzed by Northern blotting. The effect of cytokine-neutralizing antibodies on LPS-induced cathepsin S mRNA expression also was determined. RESULTS: E coli LPS increased expression of cathepsin S 12.5-fold after 12 hours; MMP-1 and MMP-3 mRNAs also were increased 2.9- and 3.5-fold, respectively. Tumor necrosis factor (TNF)-alpha, interleukin (IL-1)alpha, and IL-1beta mRNAs were markedly up-regulated after 3 hours of LPS treatment. B frag and F nuc LPS also induced TNF-alpha and cathepsin S mRNAs. E coli LPS caused a sevenfold increase in TNF-alpha secretion after 5 to 8 hours. Antihuman TNF-alpha monoclonal antibody, but not a monoclonal antibody to the low-density lipoprotein receptor, reduced the LPS-induced increase in cathepsin S mRNA by 27%, whereas neutralizing antibodies against IL-1alpha and IL-1beta did not suppress the response. Human CSMC were shown to express the toll-like receptor (TLR-2) and TLR-4 genes, which mediate the action of LPS. TLR-2 mRNA was up-regulated by TNF-alpha. CONCLUSION: CSMC respond to LPS with increased expression of pro-inflammatory cytokines and cathepsin S. Increases in cathepsin S mRNA result only in part from the rapid induction of TNF-alpha gene expression. TNF-alpha may also augment the CSMC response to LPS by increasing expression of the LPS signaling receptor, TLR-2, which probably directly mediates LPS action. These observations provide a mechanism by which gram-negative bacteria can precipitate cervical changes associated with preterm birth.

Vaginal symptoms and bacterial vaginosis (BV): how useful is self-report? Development of a screening tool for predicting BV status.

Vaginal complaints compel an evaluation of bacterial vaginosis (BV), however, many cases of BV are asymptomatic. We evaluated the sensitivity and specificity of vaginal symptoms in the diagnosis of BV and examined the utility of creating a BV screening tool using clinical, behavioural and demographic characteristics. A total of 1916 pregnant women were included in this analysis. In total, 757 women screened positive for BV and over one third of BV-positive women presented without any lower genital tract symptoms (39.4%). African American race, abnormal vaginal odour, and smoking were independently related to BV positivity. A BV screening tool including these three factors was fairly predictive of BV status with the area under the ROC curve equal to 0.669. This three-item prediction rule may be useful in identifying high- risk pregnant women in need of BV screening and, given the high specificity, accurately identify the group of BV-negative pregnant women.