Vaccination with the Crimean-Congo hemorrhagic fever virus viral replicon vaccine induces NP-based T-cell activation and antibodies possessing Fc-mediated effector functions.

Crimean-Congo hemorrhagic fever virus (CCHFV; family Nairoviridae) is a tick-borne pathogen that frequently causes lethal disease in humans. CCHFV has a wide geographic distribution, and cases have been reported in Africa, Asia, the Middle East, and Europe. Availability of a safe and efficacious vaccine is critical for restricting outbreaks and preventing disease in endemic countries. We previously developed a virus-like replicon particle (VRP) vaccine that provides complete protection against homologous and heterologous lethal CCHFV challenge in mice after a single dose. However, the immune responses induced by this vaccine are not well characterized, and correlates of protection remain unknown. Here we comprehensively characterized the kinetics of cell-mediated and humoral immune responses in VRP-vaccinated mice, and demonstrate that they predominantly target the nucleoprotein (NP). NP antibodies are not associated with protection through neutralizing activity, but VRP vaccination results in NP antibodies possessing Fc-mediated antibody effector functions, such as complement activation (ADCD) and antibody-mediated cellular phagocytosis (ADCP). This suggests that Fc-mediated effector functions may contribute to this vaccine's efficacy.

Impact of different carbapenemase-producing Enterobacterales screening strategies in a hospital setting.

BACKGROUND: The spread of carbapenemase-producing Enterobacterales (CPE) is a global health problem. Gastrointestinal tract carriage makes faeces or rectal swabs the recommended screening methods. AIM: To assess the impact of three laboratory screening strategies for CPE on positivity rates and infection prevention and control in a hospital setting in North West England from 2015 to 2017. METHODS: In a retrospective study, time to CPE-positive and -negative results, number of new CPE-positive patients identified, and number of hospital bed-days lost/wards affected were measured for each of three CPE screening strategies; culture plus phenotypic tests, culture plus polymerase chain reaction (PCR), and PCR only (phases 1, 2 and 3, respectively). FINDINGS: The fastest time to CPE results was PCR only (median: 4.0 h), then culture plus PCR (median: 47.6 h), then culture plus phenotypic tests (median: 49.8 h) (P < 0.001). The mean numbers of hospital bed-days lost per month decreased between phases 2 and 3 (P = 0.01). The mean number of wards/units affected by CPE increased from phase 1 (2.57) to phase 2 (7.71), then decreased in phase 3 (3.86). The percentage positivity rate for phases 1, 2, and 3 were 2.01, 1.38, and 1.55 respectively. From May to October, the number of new CPE-positive patients was lower for phases 1 and 3 than for phase 2. During all three phases there was a peak in the number of newly identified CPE carriers in August. CONCLUSION: This study provides evidence that using a rapid PCR to screen rectal or faeces swabs enables more timely infection prevention and control measures when compared with culture-based methods. A reduction in bed-days lost due to CPE was observed when rapid molecular screening was introduced.

Emergence of high-level azithromycin resistance in Neisseria gonorrhoeae in England and Wales.

OBJECTIVES: This study aimed to investigate the origin of high-level azithromycin resistance that emerged in isolates of Neisseria gonorrhoeae in England and Wales in 2007, and to establish methods for identifying high-level azithromycin resistance. METHODS: The Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) data from 2001-07 were examined for emerging trends in azithromycin susceptibility. Further to the identification of six high-level azithromycin-resistant isolates in GRASP 2007, an additional 102 isolates were selected on the basis of azithromycin susceptibility and geographic origin from the GRASP 2006 and 2007 collections. Susceptibility testing by Etest and disc diffusion was performed on all 108 isolates and 75 of these were typed by N. gonorrhoeae multiantigen sequence typing. RESULTS: A slight drift towards higher MICs of azithromycin was observed in the gonococcal population since 2001. Of greater concern was the first example of a shift to high-level resistance observed in six isolates in 2007. All six isolates were sequence type 649, which was not observed in any of the lower-level azithromycin-resistant isolates from 2007 or in any isolates tested from the same geographical locations. Contact tracing data for one patient suggested a link with Scotland. Disc diffusion testing of all 108 isolates showed that azithromycin, but not erythromycin, discs can differentiate between low-level and high-level resistance. CONCLUSIONS: High-level azithromycin resistance has emerged in England and Wales. Contact tracing and typing data suggest this may have originated from Scotland. Surveillance of azithromycin resistance will be key in controlling its further dissemination.

Molecular epidemiology of endemic ciprofloxacin-resistant Neisseria gonorrhoeae in Liverpool.

Ciprofloxacin-resistant Neisseria gonorrhoeae had been rarely detected on Merseyside and when found was associated with beta-lactamase producing strains, imported from abroad. However, in August 2000, two cases of infection with ciprofloxacin-resistant beta-lactamase-negative strains occurred in sexually unrelated patients with no history of foreign travel. Over the next 18 months a total of 120 patients presented with ciprofloxacin-resistant gonococci, from which 99 patient strains were available for study. Gonococcal DNA was subjected to molecular fingerprinting by polymerase chain reaction amplification followed by Taq1 digestion of their opa genes. Twelve differing opa-types were found, but 79 patients were infected with a single genotype, opa-type 1. The sexual histories of the majority of this group indicated acquisition in Merseyside. This endemic strain was further characterized by having the same amino acid substitutions on gyrA and parC genes. An endemic clone of ciprofloxacin-resistant N. gonorrhoeae has been established on Merseyside necessitating the introduction of ceftriaxone as first-line treatment. Despite the presence of 11 other clones in the city, opa type-1 strains have not yet been displaced, raising the possibility that this strain is endowed with added virulence/endemicity traits or that a number of source patients have not yet been found.

Risk factors for invasive fungal infection in neonates.

UNLABELLED: Invasive fungal infection is an uncommon, but increasing cause of morbidity and mortality in neonates. There are few controlled studies defining risk factors for the development of fungal infection in a contemporary neonatal population. This retrospective case-control study was undertaken to investigate antenatal, demographic and postnatal variables that may be potentially important in the development of fungal infection. Two gestation-matched controls were identified for each index case. Information about perinatal and demographic variables, as well as important neonatal outcomes, was obtained from case notes. Microbiological data collected included the presence of fungal colonization, and organisms responsible for invasive fungal infection. Over a 5-y period, 24 infants with invasive fungal infection and 48 controls were identified. Candida albicans was the organism identified in 75% of cases of fungal septicaemia, and in all cases complicated by fungal meningitis. Preceding fungal colonization, pulmonary haemorrhage and intrauterine growth restriction were factors significantly and independently associated with invasive fungal infection. Fifty-four percent of infants with invasive fungal infection died, and 82% of survivors developed chronic lung disease. CONCLUSION: Some new and potentially important risk factors for the development of invasive fungal infection in a contemporary population of infants admitted to a neonatal intensive care were identified.

Time to positivity of neonatal blood cultures.

AIM: To determine how long it takes neonatal blood cultures to become positive. METHODS: Data were collected retrospectively on 451 positive blood cultures from babies on a tertiary neonatal unit between January 1997 and December 1998. During the study period, the laboratory used the BacT/Alert microbial detection system. RESULTS: Complete information was available on 416 blood cultures. Twelve became positive after 72 hours, none of which were considered to be clinically significant. Of the 404 remaining cultures, 86% were positive at 36 hours, 96% at 48 hours, and 98.5% by 60 hours. If definite bacterial pathogens are considered alone, the time to positivity was 90% by 36 hours, 93% by 48 hours, and 98% by 60 hours. If definite and possible bacterial pathogens are considered (coagulase negative staphylococci taken as possible bacterial pathogens), the time to positivity was 89% at 36 hours and 97% at 48 hours. The negative predictive value, for isolation of any organism before 72 hours, of a negative blood culture was 97% at 36 hours and 99% at 48 hours. The negative predictive value for the isolation of definite bacterial pathogens only was 99.7% at 36 hours and 99.8% at 48 hours. CONCLUSIONS: A period of 36 hours is enough to rule out sepsis in the asymptomatic neonate, and a three day incubation period is sufficient to detect all clinically important infections using the BacT/Alert microbial detection system.

Magnetic interactions in the high-spin iron(III) oxooctaethylchlorinato derivative [Fe(oxoOEC)(Cl)] and its pi-cation radical [Fe(oxoOEC.)(Cl)]SbCl6.

The preparation and characterization of the beta-oxochlorin derivative [3,3,7,8,12,13,17,18-octaethyl-(3H)-porphin-2-onato(2-)]iron(III) chloride, [Fe(oxoOEC)(Cl)], and its pi-cation radical derivative [Fe(oxoOEC.)(Cl)]SbCl6 is described. Both compounds have been characterized by single-crystal X-ray structure determinations, IR, UV/vis/near-IR, and Mössbauer spectroscopies, and temperature-dependent magnetic susceptibility measurements. The macrocycles of [Fe(oxoOEC)(Cl)] and [Fe(oxoOEC.)(Cl)]SbCl6 are both saddled, and [Fe(oxoOEC.)(Cl)]-SbCl6 is slightly ruffled as well. [Fe(oxoOEC)(Cl)] shows a laterally shifted dimeric unit in the solid state, with a mean plane separation of 3.39 A and a lateral shift of 7.39 A. Crystal data for [Fe(oxoOEC)(Cl)]: triclinic, space group P1, Z = 2, a = 9.174(2) A, b = 13.522(3) A, c = 14.838(3) A, alpha = 95.79(3) degrees, beta = 101.46(2) degrees, gamma = 104.84(3) degrees. Upon oxidation, the inter-ring geometric parameters increase; the mean plane separation and the lateral shift of the dimeric unit of [Fe(oxoOEC.)(Cl)]SbCl6 are 4.82 and 8.79 A, respectively. Crystal data for [Fe(oxoOEC.)(Cl)]SbCl6: monoclinic, space group Cc, Z = 4, a = 19.8419(13) A, b = 10.027(2) A, c = 22.417(4) A, beta = 96.13(2) degrees. A broad near-IR absorption band appears at 1415 nm for the pi-cation radical, [Fe(oxoOEC.)(Cl)]SbCl6. Zero-field Mössbauer measurements at 4.2 K for both [Fe(oxoOEC)(Cl)] and [Fe(oxoOEC.)(Cl)]SbCl6 confirmed that the oxidation state of the iron atom did not change upon chemical oxidation. Solid-state magnetic susceptibility measurements for [Fe(oxoOEC.)(Cl)]SbCl6 resulted in a large temperature dependence of the magnetic moment that can best be fit with a model that includes a zero-field splitting parameter of D = 6 cm-1, antiferromagnetic intermolecular iron-iron coupling (2JFe-Fe = -0.14 cm-1), antiferromagnetic intramolecular iron-radical coupling (2JFe-r = -76 cm-1), and antiferromagnetic radical-radical coupling (2Jr-r = -13 cm-1).

Serratia marcescens pseudobacteraemia in neonates associated with a contaminated blood glucose/lactate analyzer confirmed by molecular typing.

Three episodes of Serratia marcescens pseudobacteraemia occurred on a neonatal intensive care unit. Following the first two cases, one full term and one pre-term infant, the source was identified as a glucose/lactate analyzer. Blood culture and environmental isolates of the organisms involved were indistinguishable when subjected to pulsed-field gel electrophoresis of Spe 1 digests and PCR ribotyping. Failure to recognize pseudobacteraemia in neonates results in inappropriate therapy for the individual and increased antibiotic pressures on the unit. Attention to the possibility of cross infection when using automated analyzers is required to minimize the risks of true or pseudoinfection to patients.

An assessment of triclosan susceptibility in methicillin-resistant and methicillin-sensitive Staphylococcus aureus.

Triclosan is widely used to reduce skin colonization with staphylococci and is incorporated into methicillin-resistant Staphylococcus aureus (MRSA) eradication regimes. Using an agar dilution method, the minimum inhibitory concentration (MIC) to triclosan was determined for 186 isolates of MRSA and methicillin sensitive Staphylococcus aureus (MSSA). Fourteen isolates (7.5%) were detected with a MIC > or = 1.0 part per million (ppm). There was no significant difference between the incidence of triclosan resistance in strains of MSSA and MRSA. None of 16 strains of MRSA which exhibited low-level mupirocin resistance had MIC's > or = 1.0 ppm. Increased MIC's of staphylococci to triclosan may contribute to treatment failure when used to eradicate staphylococcal carriage. We suggest that routine susceptibility testing of staphylococci against triclosan might now be indicated.

Evaluation of CHROMagar orientation medium for the identification of surveillance cultures: a novel method.

Microbiological surveillance helps prevent the spread of potentially pathogenic organisms on high-risk units. This study describes a simple method for identifying aerobic Gram-negative bacilli isolated from a neonatal intensive care unit screening programme. The identification scheme combines CHROMagar with three commonly used laboratory tests and multipoint technology. The procedure produced identical results when compared with an established identification method (Mast ID) over a three-week period. Financial evaluation suggests that significant cost savings could be achieved with the new scheme.

Blood culture volume and detection of coagulase negative staphylococcal septicaemia in neonates.

A prospective, blind study was carried out to determine: the amount of blood submitted for culture from neonates; whether small blood volumes resulted in false negative results; and whether there was a temporal relation between volume of blood cultured and time to positivity. Seventy three bottles were evaluated. They contained a median of 0.63 ml of blood. Twenty nine bottles (39.7%) contained less than 0.5 ml of blood; 21 bottles (28.8%) were positive. There were three false negative cultures, only one of which contained a blood volume below 0.5 ml. The median time to positivity was 22.4 hours. There was no correlation between blood volume cultured and time to positivity. Neonatal cultures frequently contain less than 0.5 ml of blood. False negative cultures are rare. Neonatal blood culture bottles need to be validated for blood volumes below 0.5 ml.

Microbial characteristics and severity of coagulase-negative staphylococcal septicaemia in premature neonates.

A pilot study was undertaken to assess the predictive value of characteristics possessed by coagulase-negative staphylococci in determining clinically important infection in premature neonates. No significant association was demonstrated between organism properties and clinical indices of infection. The routine use of simple measures of microbial characteristics in the assessment of neonatal septicaemia is not warranted.

Spontaneously resolving Ureaplasma urealyticum meningitis.

We report this case of a preterm infant with intraventricular haemorrhage who had Ureaplasma urealyticum isolated from the CSF together with a CSF pleocytosis both of which spontaneously cleared.

Is the endoscopic view too narrow?

Palliative laser therapy for gastrointestinal tumors is now well established. Its use however may be associated with complications not directly attributable to the laser therapy. These complications potentially decrease the quality of life which opposes the aim of treatment.

In-vitro activity of ten antimicrobial agents against penicillin-resistant Streptococcus pneumoniae.

The minimum inhibitory concentrations (MICs) of ten antibiotics were determined by the agar dilution method for 40 strains of penicillin-resistant Streptococcus pneumoniae, all of which were clinical isolates from this laboratory. The antibiotics tested were clarithromycin, erythromycin, teicoplanin, vancomycin, ceftriaxone, cefodizime, azithromycin, ramoplanin, ciprofloxacin and MDL 62873. Of these agents, clarithromycin, vancomycin, teicoplanin, ceftriaxone, ramoplanin and MDL 62873 were the most active. The role of these antibiotics as alternatives to penicillin for the treatment of infections caused by penicillin-resistant S. pneumoniae is discussed.