Decreased phagocytosis and intracellular killing of bacteria in leukocytes of geriatric patients with Clostridioides difficile infections.

INTRODUCTION: Patients suffering from a Clostridioides (C.) difficile infection have a higher overall mortality than patients with similar co-morbidities. METHODS: Whole blood samples of 15 patients with C. difficile enteritis and 15 control patients matched for age and sex were used to analyse the capacity of blood phagocytes to internalize and kill encapsulated Escherichia (E.) coli. The median age of C. difficile patients and control patients was 81 and 82 years, respectively. Blood samples were co-incubated with E. coli for 15 or 30min. After 15min of co-incubation, extracellular bacteria were killed by gentamicin for 15-45 minutes. Then eukaryotic cells were lysed with distilled water, and the number of intracellular bacteria per ml whole blood was determined by quantitative plating on agar plates. Both groups were compared by Mann-Whitney U-test. RESULTS: After 15 or 30min of co-incubation, blood phagocytes from patients with C. difficile enteritis showed a reduced density of phagocytosed or adherent bacteria in comparison to blood phagocytes from control patients (15min: p=0.046, 30min: p=0.005). The density of intracellular bacteria decreased less rapidly over time in the blood from C. difficile patients [median Δlog CFU/ml x h (25th/ 75th percentile) -0.893 (-1.893/ -0.554) versus -1.483 (-2.509/ -1.028); p=0.02]. In line with these results, the percentage of intracellularly killed bacteria was decreased in phagocytes from C. difficile-infected patients compared to controls (median intracellular killing rate 64.3% for blood phagocytes from C. difficile patients versus 81.9% for blood phagocytes from control patients within 30 min of co-incubation, p = 0.048). CONCLUSION: Blood phagocytes from patients with C. difficile enteritis exhibited a reduced capacity to phagocytose and kill bacteria in comparison to blood phagocytes from age- and sex-matched control patients. Patients with C. difficile infection may have a higher disposition to develop infectious diseases than age- and sex-matched control patients.

[Congenital malformations of the brain misinterpreted as sequelae of poliomyelitis]. / Angeborene Fehlbildungen des Gehirns als Folgezustände der Poliomyelitis verkannt.

BACKGROUND: Poliomyelitis is an infectious disease of the peripheral motor neurons, which predominantly affects children and causes residual palsies. Because of the oral poliomyelitis vaccination started in Germany in 1960 and 1962 and the following rapid decline of the incidence of this infection, the postpolio syndrome in Germany is a disease of older people. METHODS: Since 2008, we have offered a poliomyelitis outpatient consultation at the Center of Geriatrics, Protestant Hospital Göttingen-Weende and have treated 33 patients. RESULTS: The spectrum of persistent deficits after poliomyelitis ranges from palsy of single extremities to severe disability with (temporary) ventilator dependence. Many patients suffer from scoliosis or shortening of limbs of different degrees, which promotes degenerative diseases of the spinal cord and joints with secondary myelopathy, injury of spinal nerve roots or peripheral nerves or respiratory failure. The postpolio syndrome is characterized by an increase of the functional deficits after decades of compensation. The palsies of 2 of the 33 patients were not caused by poliomyelitis but by myelomeningocele and schizencephaly, respectively. CONCLUSION: The motor deficits acquired in childhood enable the majority of the patients to successfully master their lives. Because of the limited compensatory capacities of postpolio patients, even small increases in the severity of the palsy can cause a severe decline of the functional status and an impairment of the ability to live an independent life. In a substantial proportion of patients with the diagnosis poliomyelitis the symptoms are caused by other diseases.

Serological testing for syphilis in the differential diagnosis of cognitive decline and polyneuropathy in geriatric patients.

BACKGROUND: In the 19th century, neurosyphilis was the most frequent cause of dementia in Western Europe. Now dementia caused by syphilis has become rare in Germany. We studied whether routine testing of patients with cognitive abnormalities or neuropathy for antibodies against Treponema pallidum has therapeutic consequences in geriatric patients. METHODS: A Treponema pallidum electrochemiluminescence immunoassay (TP-ECLIA) is routinely performed in all in-patients treated at our institution with cognitve decline or neuropathy and no or insufficient previous diagnostic workup. Patients with a positive TP-ECLIA treated from October 2015 to January 2022 (76 months) were retrospectively evaluated. In cases of positive TP-ECLIA, further specific laboratory investigations were performed to assess whether antibiotic therapy was indicated. RESULTS: In 42 of 4116 patients (1.0%), TP-ECLIA detected antibodies directed against Treponema in serum. Specifity of these antibodies was ensured by immunoblot in 22 patients (11 × positiv, 11 × borderline values). Treponema-specific IgM was detectable in the serum of one patient, in 3 patients the Rapid Plasma Reagin (RPR) test, a modified Venereal Disease Research Laboratory test (VDRL), in serum was positiv. CSF analysis was performed in 10 patients. One patient had CSF pleocytosis. In 2 other patients, the Treponema-specific IgG antibody index was elevated. 5 patients received antibiotic therapy (4 × ceftriaxone 2 g/d i.v., 1 × doxycycline 300 mg/d p.o.). CONCLUSION: In approx. 1‰ of patients with previously undiagnosed or not sufficiently diagnosed cognitive decline or neuropathy, the diagnostic workup for active syphilis resulted in a course of antibiotic treatment.

Intrathecal Antibacterial and Antifungal Therapies.

Intrathecal administration of anti-infectives is indicated in central nervous system infections by multiresistant pathogens when drugs that can reach adequate cerebrospinal fluid (CSF) concentrations by systemic therapy are not available. Antibiotics that readily pass the blood-brain and blood-CSF barriers and/or that have low toxicity allowing an increase in the daily dosage should not be used for intrathecal therapy. Intrathecal therapy is accompanied by systemic treatment. Antibacterials indispensable for intrathecal therapy include aminoglycosides, colistin, daptomycin, tigecycline, and vancomycin. Limited experience suggests the utility of the antifungals amphotericin B and caspofungin. Intraventricular administration ensures distribution throughout the CSF compartment, whereas intralumbar dosing often fails to attain adequate antibiotic concentrations in the ventricles. The individual dose is determined by the estimated size of the CSF space and by the estimated clearance from CSF. For moderately lipophilic anti-infectives with a molecular weight above approximately 1,000 g/mol, as well as for hydrophilic drugs with a molecular weight above approximately 400 g/mol, one daily dose is normally adequate. The ventricular drain should be clamped for 15 to 120 min to facilitate the distribution of the anti-infective in the CSF space. Therapeutic drug monitoring of the trough levels is necessary only in cases of therapeutic failure.

Central nervous system infections and antimicrobial resistance: an evolving challenge.

PURPOSE OF REVIEW: Antimicrobial resistance is an increasing threat to patients also in nosocomial central nervous system (CNS) infections. The present review focusses on optimizing intravenous treatment in order to achieve sufficient concentrations of antibiotics in the different compartments of the CNS when the causative pathogens have reduced sensitivity to antibiotics or/and the impairment of the blood-cerebrospinal fluid (CSF) and blood-brain barrier is mild. RECENT FINDINGS: Experience has been gathered with treatment protocols for several established antibiotics using increased doses or continuous instead of intermittent intravenous therapy. Continuous infusion in general does not increase the average CSF concentrations (or the area under the concentration-time curve in CSF) compared to equal daily doses administered by short-term infusion. In some cases, it is postulated that it can reduce toxicity caused by high peak plasma concentrations. In case reports, new ß-lactam/ß-lactamase inhibitor combinations were shown to be effective treatments of CNS infections. SUMMARY: Several antibiotics with a low to moderate toxicity (in particular, ß-lactam antibiotics, fosfomycin, trimethoprim-sulfamethoxazole, rifampicin, vancomycin) can be administered at increased doses compared to traditional dosing with low or tolerable adverse effects. Intrathecal administration of antibiotics is only indicated, when multiresistant pathogens cannot be eliminated by systemic therapy. Intravenous should always accompany intrathecal treatment.

Reduced Clostridioides difficile infections in hospitalised older people through multiple quality improvement strategies.

OBJECTIVES: To reduce infections with Clostridioides difficile (CDI) in geriatric patients by interventions easily implementable in standard clinical care. METHODS: Prevalence and incidence of CDI between January 2015 and February 2020 were analysed (n = 25,311 patients). Pre-intervention status was assessed from April 2016 to March 2017 (n = 4,922). Between May 2017 and August 2019, a monocentric interventional crossover study (n = 4,655) was conducted including standard care and three interventions: (A) sporicidal cleaning of hospital wards, (B) probiotics and (C) improvement in personal hygiene for CDI patients. This was followed by a multicentric comparison of the interventional bundle (A + B + C) between September 2019 and February 2020 (n = 2,593) with the pre-intervention phase. In 98 CDI cases and matched controls individual risk factors for the development of CDI were compared. RESULTS: Time series analyses of CDI cases revealed a reduction in the prevalence of CDI in all three participating centres prior to the multicentric intervention phase. In the monocentric phase, no effect of individual interventions on CDI prevalence was identified. However, an aggregated analysis of CDI cases comparing the pre-intervention and the multicentric phase revealed a significant reduction in CDI prevalence. Risk factors for the development of CDI included use of antibiotics, anticoagulants, previous stay in long-term care facilities, prior hospital admissions, cardiac and renal failure, malnutrition and anaemia. CONCLUSIONS: The observed reduction in CDI may be attributed to heightened awareness of the study objectives and specific staff training. Individual interventions did not appear to reduce CDI prevalence. A further randomised trial would be necessary to confirm whether the bundle of interventions is truly effective.

[Challenges in diagnostics for intestinal tuberculosis - Pitfalls of a forgotten infectious disease: case series and literature review]. / Herausforderungen in der Diagnostik der Darmtuberkulose ­ Pitfalls einer vergessenen infektiösen Erkrankung: Eine Fallserie und Literaturübersicht.

Intestinal tuberculosis is an infectious disease of the extrapulmonary manifestation with the Mycobacteria tuberculosis complex. In developed countries, this disease is rarely seen. The clinical features are heterogeneous and unspecific. Furthermore, intestinal tuberculosis poses diagnostic challenges. Regarding intestinal tuberculosis the Ziehl-Neelsen staining for acid-fast bacillus, PCR examination and culture methods show only poor sensitivity and specificity. In this case series, we present three patients suffering from intestinal tuberculosis, who were diagnosed and treated successfully. Furthermore, we review the literature about the pitfalls of the diagnostic approaches and the treatment options of intestinal tuberculosis.

Pharmacokinetics and pharmacodynamics of antibiotics in central nervous system infections.

PURPOSE OF REVIEW: The barriers surrounding the central nervous system (CNS) together with the emergence of multiresistant pathogens pose a therapeutic challenge for the effective treatment of CNS infections. RECENT FINDINGS: In addition to vancomycin, colistin and aminoglycosides, classically used for intrathecal injection, drug concentrations in cerebrospinal fluid after intrathecal injection of daptomycin and tigecyclin were recently studied. SUMMARY: The entry of antiinfectives into the CNS compartments is determined by the physicochemical properties of the drug and by conditions in the host. The most important drug properties are lipophilicity at a neutral pH, molecular mass and drug binding to serum proteins. In clinical practice, active transport is of importance only for some drugs. In recent years, intrathecal injection of antiinfectives in addition to systemic therapy has regained attention as a means to achieve high cerebrospinal fluid concentrations. The classification of antibacterials and antifungals into time-dependent and concentration-dependent compounds is also valid for the CNS compartments.

Transmission Risk on a Neonatal Intensive Care Unit: Escherichia coli versus Klebsiella pneumoniae.

Isolation precautions required for neonatal intensive care units are part of a bundle with the aim to prevent transmission, colonization, and infection with multidrug-resistant gram-negative pathogens as neonates face an increased risk of mortality and morbidity in case of infection. The following short report describes a transmission of 3MDRGN Klebsiella pneumoniae on a neonatal intensive care unit in a university hospital in Germany. This transmission occurred even though intensified infection control measures were in place, which impressively shows the importance of surveillance, outbreak management, and awareness of contributing factors regarding outbreak situations.

Monitoring microevolution of OXA-48-producing Klebsiella pneumoniae ST147 in a hospital setting by SMRT sequencing.

Objectives: Carbapenemase-producing Klebsiella pneumoniae pose an increasing risk for healthcare facilities worldwide. A continuous monitoring of ST distribution and its association with resistance and virulence genes is required for early detection of successful K. pneumoniae lineages. In this study, we used WGS to characterize MDR blaOXA-48-positive K. pneumoniae isolated from inpatients at the University Medical Center Göttingen, Germany, between March 2013 and August 2014. Methods: Closed genomes for 16 isolates of carbapenemase-producing K. pneumoniae were generated by single molecule real-time technology using the PacBio RSII platform. Results: Eight of the 16 isolates showed identical XbaI macrorestriction patterns and shared the same MLST, ST147. The eight ST147 isolates differed by only 1-25 SNPs of their core genome, indicating a clonal origin. Most of the eight ST147 isolates carried four plasmids with sizes of 246.8, 96.1, 63.6 and 61.0 kb and a novel linear plasmid prophage, named pKO2, of 54.6 kb. The blaOXA-48 gene was located on a 63.6 kb IncL plasmid and is part of composite transposon Tn1999.2. The ST147 isolates expressed the yersinabactin system as a major virulence factor. The comparative whole-genome analysis revealed several rearrangements of mobile genetic elements and losses of chromosomal and plasmidic regions in the ST147 isolates. Conclusions: Single molecule real-time sequencing allowed monitoring of the genetic and epigenetic microevolution of MDR OXA-48-producing K. pneumoniae and revealed in addition to SNPs, complex rearrangements of genetic elements.