Klebsiella pneumoniaeoxa-48 kod urološkog bolesnika: prikaz slučaja

We present an isolate of Klebsiella pneumoniaeOXA-48 isolated in a 68-year-old man who underwent radical prostatectomy due to prostate cancer. Th e antibiotic susceptibility testing to a wide range of antibiotics was performed by disk diffusion method and determination of minimal inhibitory concentrations. Th e isolate was classified as multidrug-resistant. It showed intermediate susceptibility to imipenem and meropenem, resistance to ertapenem, and sensitivity only to colistin, amikacin, and trimethoprim-sulfamethoxazole. Th e isolate was positive for ESBLs, negative for AmpC. Polymerase chain reaction and sequencing revealed blaOXA-48, blaCTX-M-15 and blaSHV-11. The plasmid encoding OXA-48 ß-lactamase did not belong to any known PCR-based replicon typing. According to genotyping, the isolate belonged to ST37.Prikazan je izolat Klebsiella pneumoniae OXA-48 izoliran iz mokraće 68-godišnjeg muškaraca kojemu je napravljena radikalna prostatektomija zbog raka prostate. Testiranje osjetljivosti izolata na velik broj antibiotika provedeno je metodom disk difuzije kao i metodom određivanja minimalnih inhibitornih koncentracija. Izolat je klasificiran kao višestruko rezistentan. Smanjeno je osjetljiv na imipenem i meropenem, rezistentan na ertapenem, a osjetljiv samo na kolistin, amikacin i trimetoprim+sulfometoksazol. Izolat proizvodi ESBL, a ne proizvodi AmpC. Lančana reakcije polimeraze i sekvenciranje je pokazalo blaOXA-48, blaCTX-M-15 i blaSHV-11. Plazmidno kodirana OXA-48 ß-laktamaza ne pripada niti jednom poznatom PBRT. Prema genotipizaciji, izolat pripada ST37

Ceftazidime/ Avibactam for Treatment of Intrahospital Ventilator-Associated Pneumonia in COVID-19 Patients

U razdoblju pandemije koronavirusne bolesti 2019. (COVID-19) mnogi bolesnici kojima je bila potrebna invazivna mehanička ventilacija, primljeni su u jedinice intenzivnog liječenja (JIL) zbog teškog respiratornog zatajenja povezanog s bolešću COVID-19. Prijam u JIL i invazivna mehanička ventilacija neovisni su rizici za pneumoniju povezanu s ventilatorom (engl. ventilator associated pneumonia; VAP), kod koje je zabilježena visoka stopa smrtnosti i dulji boravak u JIL-u te je produljeno bolničko liječenje. Ako govorimo o uzročnicima VAP-a, Pseudomonas aeruginosa bio je jedan od glavnih gram-negativnih nefermentirajućih uzročnika ove patologije, zajedno s Burkholderia cepacia i Stenotrophomonas maltophilia u manjoj mjeri. Protiv gram-negativnih mikroorganizama otpornih na karbapeneme, ceftazidim/avibaktam (CZA) jedan je od najčešće korištenih antimikrobnih lijekova. Cilj ovog preglednog članka bio je opisati korištenje CZA u liječenju bolesnika s infekcijom COVID-19 koji su razvili VAP uzrokovan P. aeruginosa, B. cepacia i S. maltophilia, usporediti to s podatcima objavljenim u literaturi te skrenuti pozornost na kontinuiranu primjenu lijeka kao drugačijeg modaliteta u odnosu na standardni način primjene u bolusu. Unatoč visokoj smrtnosti kritično oboljelih bolesnika s COVID-om, CZA predstavlja valjanu opciju liječenja VAP-a uzrokovanog nefermentirajućim gram-negativnim mikroorganizmima.In the period of the coronavirus diseFase 2019 (COVID-19) pandemic, many patients requiring invasive mechanical ventilation were admitted to the intensive care unit (ICU) due to severe respiratory failure associated with COVID-19 infection. In fact, ICU admission and invasive ventilation increased the risk of ventilator-associated pneumonia (VAP), which is associated with a high mortality rate and longer ICU and hospital stays. Pseudomonas aeruginosa was the first causative agent of this pathology (VAP), but rare non-fermenting Gram-negative microorganisms such as Burkholderia cepacea and Stenotrophomonas maltophilia have also emerged as potential etiological agents. One of the most frequently used antibiotics against carbapenem- resistant Gram-negative microorganisms is ceftazidime/avibactam (CZA). The aim of this review article was to describe the use of CZA in a series of cases of patients with COVID-19 infection who developed difficult-to-treat VAP due to P. aeruginosa, B. cepacea and S. maltophilia and to compare it with data published in the literature, as well as to draw attention to the continuous administration of the drug as a different modality compared to the standard method of bolus administration. Despite the high mortality of critically ill patients with COVID-19, CZA, especially in combination therapy, could represent a valid treatment option for VAP caused by non-fermenting Gram-negative microorganisms

Acinetobacter Baumannii Pneumonia Associated with Mechanical Ventilation in COVID-19 Pandemic

Infekcije uzrokovane bakterijom Acinetobacter baumannii predstavljaju veliki javnozdravstveni problem. Acinetobacter baumannii kontaminira bolničko okruženje, kožu i sluznice pacijenata te se prenosi rukama osoblja uzrokujući oportunističke infekcije kao što su upale pluća povezane s mehaničkom ventilacijom, bakterijemije, infekcije rana te urinarne infekcije. Ventilatorom uzrokovana upala pluća druga je po učestalosti nozokomijalna infekcija u jedinicama intenzivnog liječenja. Vodeći čimbenik rizika za razvoj ventilatorom uzrokovane upale pluća jest invazivna mehanička ventilacija. U pacijenata s bolešću COVID-19, liječenje u jedinicama intenzivnog liječenja često je zahtijevalo intubaciju i uporabu mehaničke ventilacije izlažući ih riziku od razvoja ventilatorom uzrokovane upale pluća. S obzirom na brojna preklapanja u kliničkoj slici COVID upale pluća i upale pluća povezane s ventilatorom, teško je sa sigurnošću odrediti njezinu prevalenciju. Oštećenja pluća uzrokovana bolešću COVID-19, imunosupresivna terapija, često profilaktičko korištenje antibiotika i organizacijske teškoće – prenapučenost u jedinicama intenzivnog liječenja, manjak osoblja, potreba za zaštitom osoblja od virusa SARS-CoV-2 (engl. Severe acute respiratory syndrome coronavirus 2) infekcije i dr., pridonijeli su povećanoj pojavnosti ventilatorom izazvane upale pluća uzrokovane Acinetobacter baumannii u pacijenata oboljelih od COVID-a. Brojni mehanizmi otpornosti na antibiotike, uz posljedično sve veću prevalenciju višestruko otpornih sojeva Acinetobacter baumannii predstavljaju izazov u liječenju. U osjetljivih sojeva, monoterapija karbapenemima dovodi do pozitivnog ishoda. Liječenje karbapenem-otpornih Acinetobacter baumannii sojeva u kompliciranim infekcijama provodi se uglavnom kolistinom. Kolistin se može primjenjivati intravenski i inhalacijski te ga se preporučuje koristiti u kombinaciji s drugim djelotvornim antibioticima.Infections caused by Acinetobacter baumannii are a major public health issue. Acinetobacter baumannii contaminates the hospital environment, skin, and mucous membranes of patients and is transmitted by the hands of staff, causing opportunistic infections such as pneumonia associated with mechanical ventilation, bacteremia, wound infections, and urinary tract infections. Ventilator-associated pneumonia is the second most common nosocomial infection in the intensive care units. The leading risk factor for the development of ventilator-associated pneumonia is invasive mechanical ventilation. In the patients with COVID-19 disease, the treatment in intensive care units often required intubation and the use of mechanical ventilation, exposing them to the risk of developing ventilator-associated pneumonia. Given the numerous overlaps in the clinical picture of COVID-19 pneumonia and ventilator-associated pneumonia, it is difficult to determine its prevalence with certainty. Lung damage caused by COVID-19, immunosuppressive therapy, frequent prophylactic use of antibiotics, and organizational difficulties (overcrowding in intensive care units, staff shortages, the need to protect staff from severe acute respiratory syndrome coronavirus 2 infection, etc.) have contributed to the increased incidence of ventilator-associated pneumonia in COVID-19 patients. Numerous mechanisms of antibiotic resistance and the increasing prevalence of multidrug-resistant strains such as carbapenem-resistant Acinetobacter baumannii present a challenge in treatment. In susceptible strains, monotherapy with carbapenems leads to a positive outcome. The treatment of carbapenem-resistant Acinetobacter baumannii strains in complicated infections is carried out mainly with colistin. Colistin can be administered intravenously or by inhalation, and it’s use in combination with other effective antibiotics is recommended

Stable gastric pentadecapeptide BPC 157 in the treatment of colitis and ischemia and reperfusion in rats: new insights

AIM: To provide new insights in treatment of colitis and ischemia and reperfusion in rats using stable gastric pentadecapeptide BPC 157. ----- METHODS: Medication [BPC 157, L-NAME, L-arginine (alone/combined), saline] was bath at the blood deprived colon segment. During reperfusion, medication was BPC 157 or saline. We recorded (USB microscope camera) vessel presentation through next 15 min of ischemic colitis (IC-rats) or reperfusion (removed ligations) (IC + RL-rats); oxidative stress as MDA (increased (IC- and IC + RL-rats)) and NO levels (decreased (IC-rats); increased (IC + RL-rats)) in colon tissue. IC + OB-rats [IC-rats had additional colon obstruction (OB)] for 3 d (IC + OB-rats), then received BPC 157 bath. ----- RESULTS: Commonly, in colon segment (25 mm, 2 ligations on left colic artery and vein, 3 arcade vessels within ligated segment), in IC-, IC + RL-, IC + OB-rats, BPC 157 (10 μg/kg) bath (1 mL/rat) increased vessel presentation, inside/outside arcade interconnections quickly reappeared, mucosal folds were preserved and the pale areas were small and markedly reduced. BPC 157 counteracted worsening effects induced by L-NAME (5 mg) and L-arginine (100 mg). MDA- and NO-levels were normal in BPC 157 treated IC-rats and IC + RL-rats. In addition, on day 10, BPC 157-treated IC + OB-rats presented almost completely spared mucosa with very small pale areas and no gross mucosal defects; the treated colon segment was of normal diameter, and only small adhesions were present. ----- CONCLUSION: BPC 157 is a fundamental treatment that quickly restores blood supply to the ischemically injured area and rapidly activates collaterals. This effect involves the NO system

Klebsiella Pneumoniaeoxa-48 in a Urology Patient: Case Report

We present an isolate of Klebsiella pneumoniaeOXA-48 isolated in a 68-year-old man who underwent radical prostatectomy due to prostate cancer. Th e antibiotic susceptibility testing to a wide range of antibiotics was performed by disk diffusion method and determination of minimal inhibitory concentrations. Th e isolate was classified as multidrug-resistant. It showed intermediate susceptibility to imipenem and meropenem, resistance to ertapenem, and sensitivity only to colistin, amikacin, and trimethoprim-sulfamethoxazole. Th e isolate was positive for ESBLs, negative for AmpC. Polymerase chain reaction and sequencing revealed blaOXA-48, blaCTX-M-15 and blaSHV-11. The plasmid encoding OXA-48 ß-lactamase did not belong to any known PCR-based replicon typing. According to genotyping, the isolate belonged to ST37

Ceftazidime/ Avibactam for Treatment of Intrahospital Ventilator-Associated Pneumonia in COVID-19 Patients

U razdoblju pandemije koronavirusne bolesti 2019. (COVID-19) mnogi bolesnici kojima je bila potrebna invazivna mehanička ventilacija, primljeni su u jedinice intenzivnog liječenja (JIL) zbog teškog respiratornog zatajenja povezanog s bolešću COVID-19. Prijam u JIL i invazivna mehanička ventilacija neovisni su rizici za pneumoniju povezanu s ventilatorom (engl. ventilator associated pneumonia; VAP), kod koje je zabilježena visoka stopa smrtnosti i dulji boravak u JIL-u te je produljeno bolničko liječenje. Ako govorimo o uzročnicima VAP-a, Pseudomonas aeruginosa bio je jedan od glavnih gram-negativnih nefermentirajućih uzročnika ove patologije, zajedno s Burkholderia cepacia i Stenotrophomonas maltophilia u manjoj mjeri. Protiv gram-negativnih mikroorganizama otpornih na karbapeneme, ceftazidim/avibaktam (CZA) jedan je od najčešće korištenih antimikrobnih lijekova. Cilj ovog preglednog članka bio je opisati korištenje CZA u liječenju bolesnika s infekcijom COVID-19 koji su razvili VAP uzrokovan P. aeruginosa, B. cepacia i S. maltophilia, usporediti to s podatcima objavljenim u literaturi te skrenuti pozornost na kontinuiranu primjenu lijeka kao drugačijeg modaliteta u odnosu na standardni način primjene u bolusu. Unatoč visokoj smrtnosti kritično oboljelih bolesnika s COVID-om, CZA predstavlja valjanu opciju liječenja VAP-a uzrokovanog nefermentirajućim gram-negativnim mikroorganizmima.In the period of the coronavirus diseFase 2019 (COVID-19) pandemic, many patients requiring invasive mechanical ventilation were admitted to the intensive care unit (ICU) due to severe respiratory failure associated with COVID-19 infection. In fact, ICU admission and invasive ventilation increased the risk of ventilator-associated pneumonia (VAP), which is associated with a high mortality rate and longer ICU and hospital stays. Pseudomonas aeruginosa was the first causative agent of this pathology (VAP), but rare non-fermenting Gram-negative microorganisms such as Burkholderia cepacea and Stenotrophomonas maltophilia have also emerged as potential etiological agents. One of the most frequently used antibiotics against carbapenem- resistant Gram-negative microorganisms is ceftazidime/avibactam (CZA). The aim of this review article was to describe the use of CZA in a series of cases of patients with COVID-19 infection who developed difficult-to-treat VAP due to P. aeruginosa, B. cepacea and S. maltophilia and to compare it with data published in the literature, as well as to draw attention to the continuous administration of the drug as a different modality compared to the standard method of bolus administration. Despite the high mortality of critically ill patients with COVID-19, CZA, especially in combination therapy, could represent a valid treatment option for VAP caused by non-fermenting Gram-negative microorganisms

Comparison of clinical and sewage isolates of Acinetobacter baumannii from two long-term care facilities in Zagreb; mechanisms and routes of spread

In the previous studies OXA-23-like and OXA-24-like β-lactamase were reported among Acinetobacter baumannii in both hospitals and long-term care facilities (LTCF) in Croatia. The aim of this study was to analyze clinical and sewage A. baumannii isolates from two nursing homes in Zagreb, with regard to antibiotic susceptibility and resistance mechanisms, to determine the route of spread of carbapenem-resistant isolates. Nine clinical isolates were collected from February to May 2017 whereas in April 2017, ten A. baumannii isolates were collected from sewage of two nursing homes in Zagreb. Antibiotics susceptibility was determined by broth microdilution method. The presence of carbapenemase and extended spectrum β-lactamases (ESBL) encoding genes was explored by PCR. Conjugation and transformation experiments were performed as previously described. Genotyping was performed by SG determination, PFGE and MLST. Seven clinical isolates were positive for blaOXA24-like whereas two clinical and environmental carbapenem-resistant isolates, respectively, were found to possess blaOXA-23-like genes. Attempts to transfer imipenem resistance were unsuccessful indicating chromosomal location of blaOXA-23 gene. All carbapenem-resistant isolates belonged to SG- 1 (IC-2) whereas the rest of the isolates susceptible to carbapenems were allocated to SG- 2 (IC-1). PFGE analysis revealed low degree of genetic variability within both IC- I and IC- II. MLST corroborated that two environmental OXA-23 isolates belong to the ST-195. This study showed dissemination of OXA-23 producing A. baumannii from the nursing home into the urban sewage. Disinfection of nursing home sewage should be recommended in order to prevent the spread of resistance genes into the community sewage

The effect of pentadecapeptide BPC 157 on hippocampal ischemia/reperfusion injuries in rats

Background and purpose: We focused on the, yet undescribed, therapy effect of the stable gastric pentadecapeptide BPC 157 in hippocampal ischemia/reperfusion injuries, after bilateral clamping of the common carotid arteries in rats. The background is the proven therapy effect of BPC 157 in ischemia/reperfusion injuries in different tissues. Furthermore, there is the subsequent oxidative stress counteraction, particularly when given during reperfusion. The recovering effect it has on occluded vessels, results with activation of the alternative pathways, bypassing the occlusion in deep vein thrombosis. Finally, the BPC 157 therapy benefits with its proposed role as a novel mediator of Roberts' cytoprotection and bidirectional effects in the gut-brain axis. ----- Materials and methods: Male Wistar rats underwent bilateral clamping of the common carotid arteries for a 20-min period. At 30 s thereafter, we applied medication (BPC 157 10 µg/kg; or saline) as a 1 ml bath directly to the operated area, that is, trigonum caroticum. We documented, in reperfusion, the resolution of the neuronal damages sustained in the brain, resolution of the damages reflected in memory, locomotion, and coordination disturbances, with the presentation of the particular genes expression in hippocampal tissues. ----- Results: In the operated rats, at 24 and 72 hr of the reperfusion, the therapy counteracted both early and delayed neural hippocampal damage, achieving full functional recovery (Morris water maze test, inclined beam-walking test, lateral push test). mRNA expression studies at 1 and 24 hr, provided strongly elevated (Egr1, Akt1, Kras, Src, Foxo, Srf, Vegfr2, Nos3, and Nos1) and decreased (Nos2, Nfkb) gene expression (Mapk1 not activated), as a way how BPC 157 may act. ----- Conclusion: Together, these findings suggest that these beneficial BPC 157 effects may provide a novel therapeutic solution for stroke