Trends in hospital acquired New Delhi metallo-beta-lactamase-producing Enterobacterales in Tuscany (Italy) from 2019 to 2021: impact of the COVID-19 pandemic.

OBJECTIVES: In Tuscany, Italy, New Delhi metallo-beta-lactamase-producing carbapenem-resistant Enterobacterales (NDM-CRE) in hospitalized patients has increasingly been observed since 2018, leading in 2019 to the implementation of enhanced control measures successfully reducing transmission. We describe the NDM-CRE epidemiology during the COVID-19 pandemic in Tuscany. METHODS: Data on NDM-CRE patients hospitalized in five Tuscan hospitals were collected from January 2019 to December 2021. Weekly rates of NDM-CRE cases on hospital days in medical and critical-care wards were calculated. In March-December 2020, NDM-CRE rates were stratified by COVID-19 diagnosis. Multi-variate regression analysis was performed to assess outcomes' differences among two periods analysed and between COVID-19 populations. RESULTS: Since March 2020, an increase in NDM-CRE cases was observed, associated with COVID-19 admissions. COVID-19 patients differed significantly from non-COVID-19 ones by several variables, including patient features (age, Charlson index) and clinical history and outcomes (NDM-CRE infection/colonization, intensive care unit stay, length of stay, mortality). During the pandemic, we observed a higher rate of NDM-CRE cases per hospital day in both non-COVID-19 patients (273/100,000) and COVID-19 patients (370/100,00) when compared with pre-pandemic period cases (187/100,00). CONCLUSIONS: Our data suggest a resurgence in NDM-CRE spread among hospitalized patients in Tuscany during the COVID-19 pandemic, as well as a change in patients' case-mix. The observed increase in hospital transmission of NDM-CRE could be related to changes in infection prevention and control procedures, aimed mainly at COVID-19 management, leading to new challenges in hospital preparedness and crisis management planning.

Variable performance of different commercial systems for testing carbapenem susceptibility of KPC carbapenemase-producing Escherichia coli.

OBJECTIVES: The aim was to evaluate different methods for testing carbapenem susceptibility of Escherichia coli producing KPC-type carbapenemase. METHODS: Susceptibility to imipenem, meropenem and ertapenem was assayed using the reference broth microdilution method and several commercial methods (Vitek2, MicroScan, Etest, MIC Test Strip) starting from the same bacterial suspension. Susceptibility to imipenem and meropenem was also tested by Sensititre and disc diffusion (Bio-Rad). Results were interpreted according to EUCAST clinical breakpoints. Essential agreement (EA), category agreement (CA) and error rates were calculated as described by the International Organization for Standardization (ISO) guidelines and also considering the new EUCAST definitions. Genotypic diversity of isolates was evaluated with a RAPD profiling protocol. RESULTS: Of 54 KPC-positive E. coli isolates, 5.6%, 7.4% and 0% were susceptible standard dosing regimen (S), 55.6%, 72.2% and 0% susceptible increased exposure (I), and 38.9%, 20.4% and 100.0% resistant (R) to imipenem, meropenem and ertapenem, respectively, using the reference broth microdilution method. CA lower than 90% were observed with all systems for imipenem and meropenem using both the ISO and the modified EUCAST criteria. With ertapenem, CA >90% was observed with all methods except Vitek2. RAPD profiling revealed a remarkable genotypic diversity of the isolates, supporting that results were not biased by an oligoclonal nature of the collection. CONCLUSIONS: Commercial methods can be unreliable for testing susceptibility to carbapenems of KPC-producing E. coli. Susceptibility should be confirmed by reference broth microdilution.

Pulmonary asbestosis associated to pleural non-Hodgkin lymphoma.

We describe herein a case report of a patient affected by pulmonary asbestosis who developed a non-Hodgkin lymphoma originating in the pleura. The case is unusual for the uncommon site and because the chronic antigenic stimulation by asbestos bodies may have locally promoted an immunologic derangement.

HIV-related thrombotic thrombocytopenic purpura (TTP) as first clinical manifestation of infection.

A case of thrombotic thrombocytopenic purpura (TTP) in a 40-year-old bisexual man unaware of being HIV positive is reported. The hematologic syndrome represented the first clinical manifestation of this viral infection. The clinical picture, characterized by severe hemolytic microangiopathic anemia, thrombocytopenia, fluctuating neurologic abnormalities and fever, quickly improved after plasma exchange and corticosteroid therapy. Two blood tests showed severe depletion of the CD4+ lymphocyte count and HIV antigenemia was positive. This case represents a clinical epiphenomenon of HIV infection in an advanced phase. According to recent CDC criteria the patient should be considered in AIDS. Antiretroviral treatment was started and after nine months of follow-up there has been no relapse.

Abdominal placement of tube thoracostomy due to lack of recognition of paralysis of hemidiaphragm.

Tube thoracostomy is an invasive procedure that carries a risk of complications. We report a patient with liver cirrhosis, ascites and large left-sided pleural effusion, in whom a trocar type chest tube was inserted at the seventh left intercostal space in the midaxillary line. Chest roentgenogram revealed that the drainage tube was placed into the abdominal cavity because of a misrecognized elevation of the left hemidiaphragm. This case demonstrates that the placement of a tube thoracostomy requires caution in the identification of possible abnormalities which can lead to dangerous complications.

False positivity of tumor markers in pleural fluid of traumatic hemothorax.

Various biochemical parameters of pleural fluid have been employed to identify malignant effusions. However, many of them are also elevated in patients with nonmalignant conditions. We report on a patient with traumatic hemothorax, showing high pleural fluid concentrations of ferritin, tissue polypeptide antigen, and cancer antigen 125. This patient's pleural fluid also contained high levels of bilirubin and many macrophages containing phagocytized red blood cells, suggesting a local metabolism of hemoglobin. Our case confirms that some tumoral markers can give false positive results and suggests that their significance must be evaluated differently in bloody pleural effusions as compared with non-bloody pleural effusions.

Terlipressin-induced metabolic acidosis.

Vasopressin and its analogue terlipressin are potent vasoconstrictors which reduce mesenteric blood flow and have been used in the therapy of variceal hemorrhage. This vasoconstrictor effect applies on vascular beds throughout the body. Since in literature vasopressin is rarely described to determine lactic acidosis, we report of a patient in whom a severe metabolic (probably lactic) acidosis appeared, associated with terlipressin administration for bleeding esophageal varices. By exclusion, the temporal sequence with terlipressin therapy, the contemporary increase of arterial blood pressure and autoptic data in the case presented make likely a diagnosis of terlipressin-induced lactic acidosis. Because of the seriousness of metabolic acidosis observed in our patient we suggest a careful monitoring of acid-base parameters in patients under treatment with vasopressin analogues.

[EDTA-induced pseudothrombocytopenia]. / Pseudotrombocitopenia da EDTA.

EDTA-induced pseudothrombocytopenia is a laboratory artifact caused in vitro by platelet aggregation, due to IgG or IgM class antibodies reacting with antigenic binding site of the GP IIb glycoprotein. Pseudothrombocytopenia is rarely found (about 1% of platelets counts), but must be considered in the differential diagnosis of thrombocytopenia, since it could lead to useless investigations and therapies. We report three patients with pseudothrombocytopenia, one of whom underwent bone marrow biopsy and danazol treatment, before establishing the correct diagnosis. The absence of hemorrhagic manifestations with persisting low platelets counts led to a re-examination of peripheral blood smear and to the diagnosis of pseudothrombocytopenia. Therefore a morphological platelets evaluation and their count on citrate-anticoagulated blood must be performed in every patient under assessment for thrombocytopenia.

[Still's disease in adults: diagnostic problems]. / Malattia di Still dell'adulto: problemi diagnostici.

Still's disease is a seronegative arthritis of children which, in a limited number of cases, can affect adults. The diagnosis of adult-onset Still's disease is characterized by high fever, arthritis and negative serologic tests for rheumatoid factor and antinuclear antibodies and by at least two minor symptoms (leukocytosis, evanescent rash, serositis, hepato- or splenomegaly, and lympho-adenopathy). Since many diseases present analogous manifestations and the adult-onset Still's disease is generally diagnosed by exclusion, we report two patients, aged 26 and 39, with Still's disease, the former with a classic clinical feature, the latter with a clinical feature characterized by severe hepatic abnormalities. The determination of histocompatibility antigens can be useful because some of them (HLA-DR4 in case 1 and HLA-DRw6 in case 2) are frequently associated with the adult-onset Still's disease. The role of anti-inflammatory therapy (acetylsalicylic acid, indomethacin, steroids) must be emphasized, whose efficacy can constitute the pathognomonic element on which the diagnosis of adult-onset Still's disease can be based in a proper clinical pattern.

Malignant pleural effusions: meaning of pleural-fluid pH determination.

In 36 patients with malignant pleural effusions, we determined the pH and the glucose concentration of the pleural fluid. Twenty-one of 36 patients (58.3%) had a low pH (less than 7.30) and 15 had a normal pH (greater than or equal to 7.30; 7.13 +/- 0.12 vs. 7.37 +/- 0.05; p less than 0.0005). The patients with low pH had significantly lower glucose concentrations than those with normal pH (2.7 +/- 1.4 vs. 6.3 +/- 2.9 mmol/l; p less than 0.0005). Twenty-one of 34 patients (61.7%) had a glucose concentration lower than a cut-off value of 4.4 mmol/l; of these, 17 (81%) had a low pH. The mean survival in the low-pH group was 4.8 +/- 4.4 months, whereas the mean survival in the normal-pH group was 5 +/- 8 months (p greater than 0.4). Twelve of 36 patients (33.3%) were treated with intrapleural Corynebacterium parvum (CBP) injections. Fourteen of 21 low-pH patients (66.6%) survived more than 2 months, and 4 of them are still alive. Six of 15 normal-pH patients (40%) survived more than 2 months, and 1 of them is still alive. Three of the 5 living patients were treated with CBP (2 in the low-pH group and 1 in the normal-pH groups). Our results confirm that pH and glucose concentrations in the pleural fluid of patients with malignant effusions are frequently low. However, the survival and the response to CBP pleurodesis in patients with low-pH malignant effusions are the same as those in patients with normal-pH malignant effusions.

[Anatomical study of the fibrosing action of Corynebacterium parvum in malignant pleural effusion]. / Documentazione anatomica dell'azione fibrosante del Corynebacterium parvum nei versamenti pleurici maligni.

Intrapleural injection of Corynebacterium parvum (CBP) has recently been used for the treatment of recurrent neoplastic pleural effusions and its mechanism of action has been suggested to be either a local fibrosis-stimulating effect or immunostimulation. The case is reported of a patient with pleuritis secondary to metastases of mammary carcinoma, treated with CBP plus methylprednisolone, who died five days after the treatment because of an acute myocardial infarction. The pathologic examination showed fibrinous pleuritis with an interconnecting network between the visceral and parietal pleura.

Antithyroid antibodies during amiodarone treatment.

In 44 euthyroid and goitre-free patients, 23 treated with amiodarone (group A) and 21 treated with other antiarrhythmic drugs (group B), antimicrosomal antibodies and antithyroglobulin antibodies were determined before the beginning of treatment and after 7, 15, 30, 60, and 180 days. In group A, none of the patients had antithyroid antibodies before treatment. 1 of 15 patients (6.7%) had antimicrosomal antibodies (titre 1:100) on day 7 only, and 1 of 18 (5.5%) had antithyroglobulin antibodies (titre 1:80) on day 180. In group B. 1 of 21 patients (4.8%) had antimicrosomal antibodies (IgG class) at titre 1:400 before the beginning of treatment, which was negative on day 180, and 2 of 17 (11.8%) had antimicrosomal antibodies (titre 1:100) on day 60 only. None of these patients showed clinical and/or laboratory signs of hyper- or hypothyroidism. These data indicated that antithyroid antibodies rarely appear in amiodarone-treated patients and do not differ significantly from patients treated with other antiarrhythmic drugs. The role of autoimmunity and the meaning of antithyroid antibodies in the pathogenesis of amiodarone-induced thyroid dysfunction (mainly of hypothyroidism) in patients without pre-existent thyroid diseases is still unclear.

[Transitory efficacy of potassium perchlorate in hypothyroidism caused by amiodarone]. / Transitoria efficacia del perclorato di potassio nell'ipotiroidismo da amiodarone.

We report a case of a patient with hypothyroidism due to amiodarone. The short-term administration (1 g/die for 10 days) of potassium perchlorate (KClO4) led to normalization of serum thyroid hormone concentrations and marked reduction of thyrotropic hormone. The reduction of KClO4 (400 mg/die) and its following withdrawal led to reappearance of hypothyroidism signs. No side-effects or toxic reactions occurred during KClO4 therapy. This anion competitively inhibits thyroid iodide transport, reducing intrathyroidal iodide content and removing thyroid hormone synthesis inhibition. We suggest KClO4 therapy when amiodarone-associated hypothyroidism impairs a pre-existent cardiac disease and when a quick restoration of euthyroidism is necessary. Nevertheless, we emphasize that its effect can be transitory in cases of short-term treatment or low doses.

[Hospital pseudo-infections caused by Mycobacterium gordonae]. / Pseudoinfezioni ospedaliere da Mycobacterium gordonae.

Sputum specimens from 15 patients with respiratory disease were reported to have positive cultures for Mycobacterium gordonae, an organism generally considered to be non-pathogenic for man. None showed typical radiological changes for mycobacteriosis. Mycobacterium gordonae was also isolated from some components of the aerosol therapy instrument. Because aerosol therapy was used for 4 patients only, we were not able to establish whether the Mycobacterium gordonae was only a colonizer. We suggest that its isolation in culture must be evaluated in an adequate clinical context before concluding that it is pathogenic.

[Is malignant mesothelioma of the pleura only an occupational disease?]. / Il mesotelioma maligno della pleura è solo una malattia professionale?

Ten cases of pleural malignant mesothelioma identified histologically at the Department of General Medicine in May 1983-June 1987, are examined in this paper. Occupational risk factors and clinical features are discussed. Only one patient (10%) was subjected to occupational risk of asbestos exposure (as a smith) while the other nine patients showed a negative anamnesis for direct or indirect asbestos exposure. However, one of these patients was a tram-driver. The patients' mean age was 69 years old. 7 patients were males. 7 patients were born in an industrialized urban environment, 3 were born in an agricultural environment: all had been living in Milan for many years. Pleural fluid cytology was only useful in the diagnosis of 2 cases. This study suggests that pleural malignant mesothelioma is a neoplasm which also affects people not exposed to asbestos at work and that its frequency is increasing. The most probable cause is environmental contamination by asbestos of urban industrialized areas. Thus, it is necessary to eliminate this mineral from all manufacturing processes in which asbestos is not indispensable.

Angiotensin-converting enzyme as a possible marker for lung toxicity in amiodarone-treated patients.

Since it has been observed that in vitro amiodarone induces morphological alterations in endothelial cells similar to those observed in patients with lung toxicity and that the angiotensin-converting enzyme (ACE) seems to be a marker for perturbation of the alveolar-capillary membrane, serum ACE concentrations have been determined in 44 patients, 23 treated with amiodarone (group A) and 21 treated with other anti-arrhythmic drugs (group B), before the beginning of treatment and after 7, 15, 30, 60 and 180 days. Serum ACE concentrations in group A were lower than the basal values (15.8 +/- 5.9 mU/ml) on day 7 (12.7 +/- 4.5 mU/ml) and were higher on day 60 (17.9 +/- 3.8 mU/ml), then returned to basal values by day 180 (15.9 +/- 5.5 mU/ml), but none of the differences were statistically significant. In group B, serum ACE concentrations were significantly higher than basal values (15.2 +/- 4.0 versus 14.2 +/- 3.5 mU/ml, p less than 0.05) only on day 15. In group A serum ACE concentrations were significantly higher than in group B only on day 60 (17.9 +/- 3.8 versus 14.7 +/- 4.5 mU/ml, p less than 0.025). During the period of the study none of the patients showed any clinical or radiological signs of lung toxicity or reduction of lung diffusion capacity for carbon monoxide (DLCO). Serum ACE levels were normal even in three patients who developed pulmonary fibrosis and in four whose DLCO was reduced by more than 20% from the basal values after the study was completed.(ABSTRACT TRUNCATED AT 250 WORDS)