Journal of Infection

Clostridium difficile infection in HIV-seropositive individuals and transplant recipients

Paul J. Collini, Martijn Bauer, Ed Kuijper, David H. Dockrell — 2011-12-12

Summary: Immunocompromise is a commonly cited risk factor for Clostridium difficile infection (CDI). We reviewed the experimental and epidemiological literature on CDI in three immunocompromised groups, HIV-seropositive individuals, haematopoietic stem cell or bone marrow transplant recipients and solid organ transplant recipients. All three groups have varying degrees of impairment of humoral immunity, a major factor influencing the outcome of CDI. Soluble HIV proteins such as nef and immunosuppressive agents such as cyclosporin, azathioprine and mycophenalate mofetil modify signalling from the key cellular pathways triggered by C. difficile toxin A, although there is a paucity of data on how these factors may interact with pathways activated by toxin B. Despite this, there has been little direct investigation into the effect of immunosuppression on the pathogenesis of CDI. Epidemiological studies consistently show increased rates of CDI in these populations, which are higher in those with greater degrees of immunocompromise such as individuals with advanced AIDS not receiving combination antiretroviral therapy or allogeneic haematopoietic stem cell transplant recipients. Less consistently data suggests immunocompromise in each group also impacts rates of severe, recurrent or complicated CDI. However all these conditions are characterised by high levels of antibiotic use and prolonged hospital stay, both powerful drivers of CDI risk.

A systematic review of bacteremias in cellulitis and erysipelas

Craig G. Gunderson, Richard A. Martinello — 2011-11-14

Summary: Objectives: Because of the difficulty of obtaining bacterial cultures from patients with cellulitis and erysipelas, the microbiology of these common infections remains incompletely defined. Given the emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) over the past decade the proportion of infections due to S. aureus has become particularly relevant.Methods: OVID was used to search Medline using the focused subject headings “cellulitis”, “erysipelas” and “soft tissue infections”. All references that involved adult patients with cellulitis or erysipelas and reported associated bacteremias and specific pathogens were included in the review.Results: For erysipelas, 4.6% of 607 patients had positive blood cultures, of which 46% were Streptococcus pyogenes, 29% were other β-hemolytic streptococci, 14% were Staphylococcus aureus, and 11% were Gram-negative organisms. For cellulitis, 7.9% of 1578 patients had positive blood cultures of which 19% were Streptococcus pyogenes, 38% were other β-hemolytic streptococci, 14% were Staphylococcus aureus, and 28% were Gram-negative organisms.Conclusions: Although the strength of our conclusions are somewhat limited by the heterogeneity of included cases, our results support the traditional view that cellulitis and erysipelas are primarily due to streptococcal species, with a smaller proportion due to S. aureus. Our results also argue against the current distinction between cellulitis and erysipelas in terms of the relative proportion of infections due to S. aureus.

Control measures for invasive group A streptococci (iGAS) outbreaks in care homes

A. Cummins, S. Millership, T. Lamagni, K. Foster — 2011-11-24

Summary: Objectives: The incidence of invasive group A streptococcal infections (iGAS) is increasing in Europe, with a particularly high morbidity and mortality in the elderly. Control of outbreaks in care homes is therefore important; but is unclear how best to manage these incidents. We attempted to identify which control measures are most likely to be effective.Methods: We undertook literature searches using PubMed and Google Scholar and contacted colleagues in Health Protection Units in England for unpublished outbreaks.Results: We identified 31 outbreaks; of which 20 had sufficient detail for further analysis. Overall carriage rates of GAS in care home residents identified in outbreak investigations were 4.7%, and in staff 3.2%. In 8 outbreaks mass antibiotic prophylaxis was offered, in 9 selective prophylaxis only and in 3 none at all. Surveillance swabbing had limited influence on decisions regarding prophylaxis. A few papers mentioned the role of environmental contamination and the risk from an affected roommate.Conclusions: Pooling of results from these outbreaks failed to suggest any clear advantage to either a selective or mass antibiotic prophylaxis strategy in controlling spread. Systematic investigation and data collection from future outbreaks could be of benefit in informing future policy.

Characteristics of healthcare-associated and community-acquired Klebsiella pneumoniae bacteremia in Taiwan

2011-11-14

Summary: Objectives: Klebsiella pneumoniae is the major cause of community-onset pyogenic infections in Taiwan. We investigated the clinical features and outcomes of community-acquired (CA) and healthcare-associated (HCA) infections among community-onset K. pneumoniae bacteremia.Methods: Adult patients with community-onset monomicrobial K. pneumoniae bacteremia were analysed retrospectively at a medical centre in Taiwan over a 4-year period. We compared the clinical characteristics of patients from the CA and HCA groups and identified the risk factors for infection-related mortality.Results: In a total of 372 patients, HCA infections were observed in 44%. The HCA group had higher Charlson score, the Acute Physiology and Chronic Health Evaluation, version II (APACHE II) score, frequency of malignancy, rates of respiratory tract infection and bacteremia from unknown sources, and higher mortality than the CA group. Diabetes and liver abscess were predominant in the CA group. Whereas old age, APACHE II score >15, malignancy, liver cirrhosis, chronic renal failure, respiratory tract infection, skin and soft tissue infection, and inappropriate antimicrobial therapy were predictors for mortality, HCA bacteremia was not.Conclusions: HCA bacteremia showed different characteristics and higher mortality than CA bacteremia, but HCA infection was not an independent risk factor for mortality.

Orthopaedic-implant infections by Escherichia coli: Molecular and phenotypic analysis of the causative strains

2011-11-17

Summary: Objectives: Little is known about Escherichia coli Orthopaedic Implant Infections (OII) pathogenesis. Thus, we compared 30 clinical strains isolated in this context with 30 clinical strains of faecal origin, in order to identify phenotypic and genetic features related to E. coli OII.Methods: Phylogenetic analysis and detection of 19 virulence genes were performed by PCR. Ability to form biofilm was studied using the crystal violet reference method and the innovative BioFilm Ring Test®.Results: Most of the OII isolates (56.7%) belonged to the virulence-associated phylogenetic group B2, but did not present a specific set of virulence factors. S fimbriae was the only adhesin significantly associated with OII isolates. Isolates varied greatly in their ability to form biofilm but OII isolates did not produce significantly more biofilm in vitro than isolates of faecal origin, whatever the method used.Conclusions: Neither a specific pathogenic signature nor an increased ability to form biofilm in vitro was detected in E. coli strains isolated from OII. Nevertheless, genetic properties of these isolates could provide a clue to their origin. Hence, we found that virulence factors of uropathogenic strains and urological disorders were frequently detected among our OII cohort.

Colonisation and infection due to Enterobacteriaceae producing plasmid-mediated AmpC β-lactamases

2011-11-24

Summary: Objectives: To investigate the epidemiology and clinical features of infections caused by Enterobacteria producing plasmid-mediated AmpC β-lactamases (pAmpC), which are emerging as a cause of resistance to extended-spectrum cephalosporins.Methods: A prospective multicentre cohort of patients with infection/colonisation due to pAmpC-producing Enterobacteriaceae was performed in 7 Spanish hospitals from February throughout July 2009. pAmpCs were characterised by PCR and sequencing.Results: 140 patients were included; organisms isolated were Escherichia coli (n = 100), Proteus mirabilis (n = 20), Klebsiella pneumoniae (n = 17), and others (n = 3). Overall, 90% had a chronic underlying condition. The acquisition was nosocomial in 43%, healthcare-associated in 41% (14% of those were nursing home residents), and community in 16%. Only 5% of patients had no predisposing feature for infection with multidrug-resistant bacteria. Nineteen percent of patients were bacteraemic. Inappropriate empirical therapy was administered to 81% of bacteraemic patients, who had a crude mortality rate of 48%. The most frequent enzyme was CMY-2 (70%, predominantly in E. coli and P. mirabilis) followed by DHA-1 (19%, predominantly in K. pneumoniae).Conclusion: pAmpC-producing Enterobacteriaceae caused nosocomial, healthcare-associated and community infections mainly in predisposed patients. Invasive infections were associated with high mortality which might be partly related to inappropriate empirical therapy.

Fatal Neisseria meningitidis serogroup X sepsis in immunocompromised patients in Spain. Virulence of clinical isolates

Diego Vicente, Olatz Esnal, Emilio Pérez-Trallero — 2011-11-17

Summary: Background: Neisseria meningitidis X (NmX) is a minority meningococcus serogroup for which no vaccine is available. Huge meningococcus X outbreaks occurred in West Africa but developed countries have reported only sporadic cases. Two invasive fatal cases are presented.Methods: Isolates were characterized by serogrouping (latex agglutination and genogroup X-specific polymerase-chain-reaction), PorA and FetA typing, multilocus sequence typing and pulsed-field gel electrophoresis. Immunocompetent female balm/C mice inoculated intraperitoneally were use to test virulence of invasive and carrier isolates.Results: Until April 2010, NmX was absent among 868 invasive meningococci characterized in the Basque Country in a 20-year period. In April 2010, two fatal NmX: P1.21,16: F5-5/ST750 episodes were detected in unrelated immunodeficient patients. After analysis of 803 meningococcal isolates from asymptomatic carriers obtained between 1988 and 2010, eight NmX isolates were detected. The genotype of the two invasive isolates bore no relation to any of the NmX isolates detected in healthy individuals from the Basque Country or to isolates from outbreaks in Africa.Conclusions: NmX isolates in the north of Spain can cause severe disease in humans, despite their low prevalence. The in vivo animal study showed that virulence of isolates was more closely associated with the genotype than with the serogroup.

Questionable role of interferon-γ assays for smear-negative pulmonary TB in immunocompromised patients

2011-11-21

Summary: Objective: The purpose of this study was to examine the usefulness of the TST and the interferon-γ release assays (IGRA) for diagnosing smear-negative pulmonary TB in immunocompromised patients in an intermediate TB burden.Methods: We conducted a prospective study enrolling 119 immunocompromised participants with suspected smear-negative pulmonary TB in Seoul, South Korea. Clinical assessment, TST, QuantiFERON-TB Gold In Tube (QFT-GIT), and T-SPOT.TB were performed in immunosuppressed condition.Results: All participants were categorized according to the type of immunosuppression: 29 patients with diabetes mellitus, 53 with malignancy, 23 with taking immunosuppressive drugs, and 14 with end stage renal disease. IGRA sensitivity and specificity (95% CI) were: QFT-GIT [59.0% (44.9–72.0)] and [61.3% (54.4–67.6)] and T-SPOT.TB [72.0% (54.2–86.2)] and [42.3% (33.8–49.1)], respectively. For TST, sensitivity was 41.2% (28.3–50.8) and specificity was 91.8% (85.8–96.30). The sensitivities of the three diagnostic methods tended to be lower in the immunosuppressive drug group than in other groups (QFT-GIT 11.1%, T-SPOT.TB 40.0% and TST 25.0% in patients with taking immunosuppressive drugs). Among 111 patients who underwent a chest CT examination, there were no significant differences in the CT findings between the immunocompromised TB and non-TB patients.Conclusions: The IGRAs and TST had no value as a single test either to rule-in or rule-out active TB in immunocompromised patients in an intermediate burden.

Improving the timeframe between blood collection and interferon gamma release assay using T-Cell Xtend®

J.J.M. Bouwman, S.F.T. Thijsen, A.W. Bossink — 2011-11-21

Summary: Vacutainer CPT tubes require blood samples for TSPOT.TB to be processed within 8 h. In this study we evaluated the ability of T-Cell Xtend to maintain the number and function of lymphocytes after 24 and 48 h of blood storage, giving similar test results as in freshly isolated specimens.Methods: Whole blood specimens from 59 individuals were collected in Vacutainer CPT tubes (CPT) and lithium heparin (LH) tubes. CPT tubes were processed within 8 h. T-Cell Xtend was added to LH tubes after 24 or 48 h. We also left LH tubes untreated for 48 h. Total number of white blood cells (WBC) and proportions of lymphocytes and granulocytes were determined in the isolated Peripheral Blood Mononuclear Cells (PBMC). We also evaluated the performance of T-Cell Xtend in the TSPOT.TB assay.Results: PBMC yields from T-Cell Xtend treated LH samples did not differ from PBMC yields from CPT tubes, but T-Cell Xtend had a pronounced effect on the proportions of lymphocytes and granulocytes. The mean lymphocyte percentage in PBMCs isolated from fresh CPT blood was 84.31 ± 1.14% (at t = 48 h), but was decreased to 52.72 ± 3.34% (p < 0.05) in untreated LH blood (at t = 48 h). This effect was neutralized by T-Cell Xtend (85.44 ± 0.74%). We observed a similar but opposite effect on granulocytes: The mean proportion in untreated LH blood was increased to 40.9 ± 3.67% (p < 0.001) compared to CPT blood (8.26 ± 0.89%). Treatment of LH samples with T-Cell Xtend (48 h) restored the proportion of granulocytes to 8.47 ± 0.61%. Enumeration of spots in the TSPOT.TB assay demonstrated good agreement between CPT and T-Cell Xtend results, even after 48 h.Conclusions: T-Cell Xtend efficiently removes granulocytes from PBMC suspensions and increases the proportion of lymphocytes. TSPOT.TB results from T-Cell Xtend treated blood samples are at least comparable to the results obtained from the current CPT method. Use of standard lithium heparin blood combined with T-Cell Xtend allows up to 48 h storage of blood samples for batched processing and may further decrease the rate of indeterminate TSPOT.TB results.

Hepatic safety of efavirenz in HIV/hepatitis C virus-coinfected patients with advanced liver fibrosis

2011-11-28

Summary: Objective: To assess the frequency of severe liver toxicity in HIV/hepatitis C (HCV)-coinfected patients with advanced liver fibrosis receiving efavirenz (EFV)-based antiretroviral combinations.Methods: One hundred and eighty-nine previously antiretroviral naïve, HIV/HCV-coinfected patients, who started a regimen including two nucleoside analogues plus EFV, and in whom the presence or absence of advanced liver fibrosis could be established, were retrospectively analyzed. Liver fibrosis was evaluated according to a stepwise algorithm including liver biopsy, transient elastography and FIB-4 index.Results: Fifty-six patients had advanced fibrosis – 25 with cirrhosis – and 133 did not. Three (5.4%) subjects with and 9 (6.8%) (p=0.717) without advanced fibrosis developed grade 3–4 transaminase elevation (TE). Grade 4 total bilirubin elevation was seen in 5 (8.9%) patients with advanced fibrosis and in 1 (0.8%) without it (p=0.003). Liver events led to EFV discontinuation in 10 (5.3%) patients, 6 (10.7%) with and 4 (3%) without advanced fibrosis (p=0.031).Conclusions: The hepatic tolerability of EFV was good in HIV/HCV-coinfected patients with advanced liver fibrosis. The frequency of grade 3–4 TE was similar to that observed in patients without advanced fibrosis, there was no death attributable to liver failure caused by drug toxicity and the rate of EFV discontinuations due to liver events was low.

Seroprevalence of and risk factors for Toscana and Sicilian virus infection in a sample population of Sicily (Italy)

2011-11-21

Summary: Objective: The present study aimed to assess seroprevalence of and risk factors for Toscana (TOSV) and Sicilian (SFSV) virus infections in a sample of Sicilian subjects.Methods: A cross-sectional seroepidemiological study was conducted on 271 individuals. Each participant completed a self-administrated questionnaire and provided a serum sample which was analyzed for the presence of IgG specific anti-TOSV and anti-SFSV viruses.Results: Overall, 90 subjects (33.2%) were positive for TOSV IgG, 25 (9.2%) were positive for SFSV IgG and 11 (4%) were positive for both the viruses. A higher risk for TOSV seropositivity was found in participants who were older (adjOR = 1.02 per year; 95% CI = 1.01–1.03), having a pet living outdoors (adjOR = 2.62; 95% CI = 1.42–4.83) and being obese (adjOR = 2.37; 95% CI = 1.06–5.30).Conclusions: TOSV seroprevalence appears to be relatively high in Sicilian general population, especially in older adults, representing a potential public health concern. The observations that seropositivity for TOSV was not significantly associated with SFSV seropositivity, and none of the risk factors associated with TOSV were associated with SFSV seem to suggest that these two phleboviruses may have different ecology and transmission pathways.

Clinical characteristics and outcomes of diabetic patients who were hospitalised with 2009 pandemic influenza A H1N1 infection

2011-11-28

Summary: Objectives: To describe demographic and clinical data and outcomes of severe cases of 2009 pandemic influenza A H1N1 (pH1N1) infections for persons with diabetes.Methods: We selected all person with diabetes (N = 252) among severe laboratory confirmed cases reported to the Spanish Surveillance System for detection of pH1N1 from June through December, 2009. One patient without diabetes matched by age and sex was selected. Collected variables included demographic characteristics, underlying medical conditions, outcome, clinical course and treatment.Results: Among those suffering diabetes only 15.9% did not report any other underlying condition. 38% of diabetic patients and 27.4% of non diabetic patients were admitted to ICU (p = 0.008). Thirty subjects suffering diabetes and fifteen without the disease died (11.9% vs. 6%[p = 0.019]).Multivariable analysis showed that the independent risk factors for ICU admission or death were suffering cardiovascular disease (OR = 2.28), morbid obesity (OR = 2.08) and antiviral treatment started after 48 h of onset of symptoms (OR = 1.89). Suffering diabetes was not independent risk factors for ICU admission or death after adjusting for covariates.Conclusions: The worse outcome among diabetes sufferers could be a consequence of the higher prevalence of comorbid underlying medical conditions but not diabetes itself. Further prospective studies are needed to verify these results.

Lethal human neutropenic entercolitis caused by Clostridium chauvoei in the United States: Tip of the iceberg?

Jill E. Weatherhead, David J. Tweardy — 2011-09-19

Summary: The patient is a 44-year-old woman with metastatic grade 3 intra-ductal carcinoma of the breast who was started on palliative chemotherapy (docetaxel) 10 days prior to admission and presented to the emergency center complaining of diffuse abdominal pain and generalized weakness. CT abdomen showed diffuse bowel wall thickening from the cecum to the transverse colon with free fluid in the pelvis. The patient was neutropenic on admission (absolute neutrophil count of 600 cells/μl). She received antibiotics for 21 days for neutropenic enterocolitis. Blood culture isolate from admission was sent for 16s rRNA gene sequencing, which identified Clostridium chauvoei. While C. chauvoei has a long history of veterinary importance, this is the first documented case of infection caused by C. chauvoei in a human in the United States. C. chauvoei has a close phylogenetic relationship with C. septicum making the two species difficult to differentiate using conventional microbiologic methods. With increased use of more reliable detection methods the actual prevalence of C. chauvoei causing human disease may be higher than currently recognized.

Risk factors for Mycobacterium chelonae-abscessus pulmonary disease persistence and deterioration

2011-11-14

We read with interest regarding “Clinical relevance of Mycobacterium chelonae-abscessus group isolation in 95 patients”, which was recently published in this journal. In this article, van Ingen J et al found that treatment for M. chelonae-abscessus (M. che-abs) pulmonary disease as defined by the 2007 American Thoracic Society (ATS) criteria yielded only limited results. Furthermore, five patients who met the ATS criteria and either received short regimens, observation or first-line anti-tuberculosis drugs considered inactive against rapidly growing nontuberculous mycobacterium (NTM) also had favorable outcome. The suggested lengthy treatment course and potential adverse effects can further hamper physicians from initiating therapy against M. che-abs according to current guideline. From a clinical standpoint, identifying patients who are likely to have persistent pulmonary disease and radiographic deterioration due to M. che-abs infection is important because they may require prompt treatment.

Isolation of Bisgaardia hudsonensis from a seal bite

N.J. Davison, J.E.F. Barnett, R.D. Ayling, A.M. Whatmore, G. Foster — 2011-11-14

We read with interest the recent case report of Bisgaardia hudsonensis from a patient with an infected seal bite. We notice with some concern that there was no mention of whether testing for Mycoplasma was attempted as Mycoplasma phocicerebrale is the most commonly isolated organism from “seal finger” or “speck finger”, an infection that can occur from handling seals or from infected bite wounds. Studies by our group on UK common and grey seals recovered M. phocicerebrale from various sites, including the teeth. Furthermore our studies also found M. phocicerebrale to be the most common organism isolated from infected bite wounds following aggressive interactions between seals. The GP in this case selected to use amoxicillin/clavulanic acid treatment and not tetracycline, the treatment indicated for seal finger cases. The eventual response of the patient to amoxicillin/clavulanic acid would suggest that Mycoplasma infection was not the cause on this occasion. We feel that it is of major importance however, to emphasise the association of M. phocicerebrale with seal finger, the importance of testing for Mycoplasma infections in all suspect cases and the use of prompt and appropriate antibiotic treatment for this serious but little known infection, which can often have significant sequelae.

Alloiococcus otitidis: An emerging pathogen in otitis media

2011-11-14

We read with interest the article published on microbiology of chronic otitis media with effusion (OME) in a Korean population which reported a high frequency of coagulase-negative Staphylococcus, Pseudomonas, methicillin resistant Staphylococcus aureus (MRSA) and methicillin-susceptible S. aureus (MSSA). In our studies of Australian children treated surgically for OME, we found similar proportions of S. aureus and Streptococcus pneumonia (SP) but lower proportions of Pseudomonas and higher proportions of Corynebacterium isolates. The predominant organism was Alloiococcus otitidis (AO), usually detected by PCR in patients with acute otitis media (AOM) and OME ().

Cerebral abscesses in patients with bacterial meningitis

Kin K. Jim, Matthijs C. Brouwer, Arie van der Ende, Diederik van de Beek — 2011-11-21

Cerebral abscesses have been reported as an uncommon complication of community-acquired bacterial meningitis in adults. We investigated the incidence, causative organisms, and outcome of cerebral abscesses in adults presenting with community-acquired meningitis in a nationwide prospective cohort study.

Severity assessment of influenza virus infection in secondary care

2011-11-21

We read the comprehensive review on pH1N1 severity assessment by Singanayagam and colleagues with interest. They highlight the limitations of severity assessment tools and factors associated with severe disease with pH1N1 infection, as had previously been shown for influenza prior to pH1N1. The majority of evidence recently has concentrated on pH1N1 infection only, most of which was collected during the first wave of cases in 2009/2010 in both the UK and elsewhere. It is not clear how applicable this is in the setting of pH1N1 becoming the predominate seasonal influenza virus, particularly with co-circulation of influenza B virus, as was the case in the UK in the winter of 2010–2011. Here we describe factors associated with admission to critical care in adult patients attending our hospitals with confirmed influenza, of any type, during the winter of 2010–2011. We also propose an admission and severity assessment pro forma which we intend to use prospectively in the forthcoming influenza season.

Enteric fever in returning travellers: Role of outpatient parenteral antibiotic therapy

B. White, J.E. Coia, C. Sykes, H. Mather, R.A. Seaton — 2011-11-24

In a recent review of imported enteric fever in Leicester, UK, a shift in therapy from ciprofloxacin to ceftriaxone and azithromycin was observed between 1999 and 2009, reflecting reduced ciprofloxacin sensitivity (MIC 0.125–1 mg/L) amongst Salmonella enterica isolates across Asia.