In vitro activities of antibiotic combinations against mature biofilms of ventilator-associated pneumonia isolates.

Background: The authors aimed to determine the efficacy of frequently used antibiotics, alone or in combination, against biofilms of ventilator-associated pneumonia isolates. Materials & methods: The authors determined the MICs, minimum biofilm inhibitory concentrations and minimum biofilm eradication concentrations of meropenem, ciprofloxacin and colistin as well as their combinations against planktonic forms and biofilms of Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii clinical isolates. Results: Generally, the minimum biofilm inhibitory concentrations and minimum biofilm eradication concentrations of the antibiotics were 1000-fold higher than their MICs, and synergy was provided by different concentrations of meropenem-colistin and meropenem-ciprofloxacin combinations with checkerboard and time-kill curve methods. Conclusion: The combination of meropenem and ciprofloxacin seems to be a good candidate for the treatment of biofilm-associated infections; none of the concentrations obtained as a result of the synergy test were clinically significant.

The effect of tocilizumab, anakinra and prednisolone on antibody response to SARS-CoV-2 in patients with COVID-19: A prospective cohort study with multivariate analysis of factors affecting the antibody response.

OBJECTIVES: Disease severity, previous medications and immunosuppressive agents could affect the antibody response against SARS-CoV-2. This study aimed to analyze variables affecting the humoral response to SARS-CoV-2. METHODS: This prospective cohort study included adult patients who recovered from COVID-19 and were admitted to a COVID-19 follow-up unit. Eight patient groups were defined in accordance with the results of thoracic computed tomography (CT), SARS-CoV-2 PCR test, and tocilizumab or anakinra use during active disease. Anti-S IgG antibodies were determined by ELISA in serum samples. Anti-S positive and negative cases were compared. RESULTS: A total of 518 patients were included in the study. SARS-CoV-2 IgG antibodies were positive in 82.8% of patients. SARS-CoV-2 PCR positivity, extent of lung involvement on CT, and time to antibody testing were independently associated with antibody positivity. Tocilizumab, anakinra or prednisolone use was not a factor affecting the antibody response. The rate of antibody response and sample/CO values among antibody-positive patients showed a linear relationship with the extent of lung involvement on CT. CONCLUSIONS: The use of tocilizumab, anakinra and prednisolone for COVID-19 did not affect the antibody response against SARS-CoV-2. The main driver of antibody response among patients with COVID-19 was the extent of pulmonary involvement on CT.

Hyponatremia Is Predictive of HSV-1 Encephalitis among Patients with Viral Encephalitis.

Encephalitis is an inflammatory process involving the brain parenchyma associated with neurologic dysfunction. The main causes of infectious encephalitis are viruses, including Herpes simplex virus type 1 (HSV-1). As the mortality rate of HSV-1 encephalitis could be reduced with early acyclovir treatment, it is imperative to distinguish HSV-1 encephalitis from other type of viral encephalitis as early as possible. However, sophisticated methods for definitive diagnosis of HSV-1 encephalitis are not readily available. We aimed to explore distinctive clinical and laboratory features of HSV-1 encephalitis. All of the adult patients with viral encephalitis hospitalized between 2011-2017 were enrolled, including 16 patients with HSV-1 encephalitis and 51 patients non-HSV-1 viral encephalitis. Determination of viruses in cerebrospinal fluid was performed by PCR tests. Female sex, hyponatremia, and abnormalities in MRI were independently associated with HSV-1 encephalitis (p < 0.05 for each). In particular, hyponatremia (< 135 mEq/L) was found in nine patients with HSV-1 encephalitis (56.3%) and 10 patients with non-HSV-1 viral encephalitis (19.6%) (p = 0.005). As serum sodium is determined easily and quickly in clinical practice, the presence of hyponatremia among patients with viral encephalitis could be helpful for the early diagnosis of HSV-1 encephalitis before cerebrospinal fluid PCR results were available. Moreover, the presence of positive finding in MRI could further support the diagnosis. This is the first study that compared the serum sodium levels among patients between HSV-1 and non-HSV-1 viral encephalitis. We thus propose the diagnostic value of hyponatremia for HSV-1 encephalitis.

Hematologic Adverse Effects of Prolonged Piperacillin-Tazobactam Use in Adults

Objective: We aimed to find the incidence and risk factors of hematologic adverse effects of piperacillin-tazobactam (TZP). Materials and Methods: Adult patients who used TZP for more than 10 days were included in the study. Results: The incidence of leukopenia, neutropenia, and eosinophilia in 110 TZP therapy episodes was found to be 16.3%, 10%, and 10%, respectively. Lower Charlson Comorbidity Index score, lower initial leukocyte count, combination of TZP with another antibiotic, and total duration of TZP therapy were found to be independent risk factors for leukopenia, while initial higher eosinophil count (IHEC) and usage of TZP for >20 days were independent risk factors for neutropenia and IHEC and total duration of TZP therapy were independent risk factors for eosinophilia. Conclusion: Longer duration of therapy, combination with other antibiotics, younger age with fewer comorbidities, and IHEC could result in hematologic adverse effects in patients treated with TZP. Patients with IHEC may be more prone to allergic reactions, so immunological mechanisms may facilitate the development of hematological adverse effects of TZP.

[A case of coccidioidomycosis in Turkey imported from the United States of America]. / Türkiye'de Amerika Birlesik Devletleri kaynakli bir koksidiyoidomikoz olgusu.

Coccidioidomycosis caused by Coccidioides immitis or Coccidioides posadasii is a rare infectious disease except in endemic regions. In this report the third documented imported case of coccidioidomycosis in Turkey was presented. A thirty-year-old male patient was admitted to our hospital with fever and purulent drainage from his chest tube. He had worked in Arizona, USA, until 4 months before this presentation. While in Arizona, he experienced cough and hemoptysis and was diagnosed as pulmonary coccidioidomycosis. He was treated with itraconazole for two months and he had no symptoms for 3 years. He then returned to Turkey and 2 months after his return to Turkey, he was admitted to another hospital in Istanbul with dyspnea and diagnosed as hydro-pneumothorax, and pleural fluid obtained from the inserted chest tube was found to be purulent. One gram of BID amoxicillin-clavulanate was given. Physical examination on admission revealed a purulent drainage on the right side chest tube, a temperature of 38.5°C and decreased breath sounds on the right lung. Piperacillin-tazobactam 3 x 4.5 g intravenous and fluconazole 400 mg intravenous once daily were started. Human immunodeficiency virus test was negative. Gram-negative diplococci and rods, gram-positive cocci and septate hyphae were seen in the Gram stain of his pleural fluid. Pleural fluid culture revealed Moraxella catarrhalis after 24 hours incubation and a mold after 72 hours of incubation. Anti-coccidioidal antibodies were found positive in a titer of 1/2. Hydro-pneumothorax, atelectasis and a 3 mm nodules in the right lung were seen in his thorax CT. The patient's pleural fluid and the culture plates were sent to the Public Health Institute of Turkey, Mycology Reference Laboratory (PHIT-MRL), with a clinical suspicion of coccidioidomycosis. The specimen and plates were submitted to the PHIT-MRL Bio Safety Level-3 laboratory for mycological evaluation. The microscopic examination of 15% KOH preparations of pleural fluid specimens revealed septate hyphae which appear to be in the early stages of forming arthroconidia. The pleural fluid culture grew buff-white coloured colonies with aerial hyphae, which were suspected of being a Coccidioides spp. The strain was identified as C.immitis/posadasii by direct microscopy and culture, and subsequently confirmed by the FDA-approved DNA probe. DNA sequence analysis of the ITS and D1/D2 rDNA regions confirmed the isolate to be C.posadasii species [ITS 100% match to GenBank Accession No. AB232901 (630/630 base pair match), and D1/D2 100% match to GenBank Accession No. AB232884 (617/617 base pair match)]. ITS1 and ITS2 barcode analysis also confirmed the species to be C.posadasii, which is the species endemic in Arizona. Susceptibility testing was performed according to Clinical and Laboratory Standards Institute M38-A2 guidelines in the Fungus Testing Laboratory of the University of Texas Health Science Center at San Antonio and minimal inhibitory concentration values were; 0.125 µg/ml for amphotericin B, posaconazole and voriconazole, 0.5 µg/ml for itraconazole and 8 µg/ml for fluconazole. He had decortication of the pleura and was discharged from hospital after six weeks treatment with intravenous fluconazole which was continued orally for one year. Anti-coccidioidal antibodies were negative after two months of treatment. The patient is currently asymptomatic. The presented case is the third case reported from Turkey and provides additional contribution to the existing literature with regard to the appearance of arthroconidium, which is the unusual hyphal form, instead of the expected spherules in the infected tissue.

[Is there a relationship between rectal colonization and nosocomial infection of patients in intensive care unit?]. / Yogun bakim birimindeki hastalarin rektal kolonizasyonu ile hastane enfeksiyonu arasinda bir iliski var mi?

Nosocomial infections caused by multidrug-resistant (MDR) microorganisms are a major problem in intensive care units (ICUs) with high mortality and morbidity rates and the prior colonization is an important risk factor for these infections. The aim of this study was to investigate the prevalence of rectal colonization of MDR microorganisms and the association between the microorganisms that caused colonization and infection in the patients with nosocomial infections in ICUs. Rectal swabs were obtained on the day of 0, 3, 7, 14, 21 and weekly thereafter from 80 patients over 18 years of age hospitalized in ICU for more than 48 hours, and cultured for vancomycin-resistant enterococcus (VRE), methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum ß-lactamase (ESBL)- producing gram-negative bacilli (GNB) and carbapenem-resistant enteric and nonenteric bacilli. Patients whose rectal swabs were not obtained on admission (on the day of 0), were excluded even they were hospitalized more than 48 hours. Bile esculin agar containing 64 µg/mL ceftazidime and 6 µg/mL vancomycin, chromogenic MRSA agar and blood agar media, MacConkey agar containing 1 mg/L ceftazidime and ceftriaxone, and 5 mL tryptic soy broth media containing 10 µg imipenem and meropenem discs were used for identification. Identification of GNB was determined by conventional methods and ESBL production was determined by double-disc synergy test. Patients have been followed up for nosocomial infections. Bacterial identification and antibiotic susceptibility tests were performed with standard microbiological methods. In 37 (46%) of the 80 patients, at least one MDR microorganism was isolated in rectal swab cultures on the day of 0. The most common microorganisms were ESBL-positive E.coli (19%), followed by ESBL-positive K.pneumoniae (13%), carbapenem-resistant P.aeruginosa (10%), ESBL-positive K.oxytoca (3%), MRSA (1%), VRE (1%), carbapenem-resistant Acinetobacter sp. (1%) and carbapenem-resistant K.pneumoniae (1%), respectively. The number of microorganisms isolated from rectal swab cultures on the following days have increased, and on the 7th day, the rate of the patients with rectal colonization ascended to 72%. Out of 80 patients, 52 (65%) had nosocomial infections in the follow-up and the mean duration of infection development was 11.8±9.9 days in these patients. Patients with and without rectal colonization were compared in terms of subsequent nosocomial infection rates. While no statistically significant difference has been detected between two groups on the day of 0, patients with rectal colonization detected on the day of 3 and 7, had a significantly higher incidence of nosocomial infections (p=0.02, p=0.01). Among the patients with ESBL-positive GNB, carbapenem-resistant K.pneumoniae, carbapenem-resistant P.aeruginosa and VRE infections, the same microorganisms have been isolated in the rectal swab cultures taken before the development of infection. This result was statistically significant for each of these microorganisms (p=0.00-0.03). However, such a correlation was not observed for Acinetobacter infections. Since MRSA infections developed in only two patients, no istatistical analysis has been done for this microorganism. In conclusion, our data suggest that MDR microorganisms that cause nosocomial infections, initially colonize the gastrointestinal tract, and early detection of colonized patients in ICUs may help an effective infection control by preventing the spread of these resistant microorganisms.

[Nosocomial respiratory syncytial virus infections in three cases in a bone marrow transplantation unit]. / Kemik iligi nakli ünitesinde yatan üç olguda nozokomiyal solunum sinsityal virus enfeksiyonu.

Here we report the spread of respiratory syncytial virus (RSV) infection among three patients, who were hospitalized in an adult hematopoetic stem cell transplantation (HSCT) unit because of hematologic diseases, and effects of RSV infection on post-transplant outcome. The patients were placed into reverse isolation for administration of preparative regimens (high dose chemotherapy) in HSCT unit with high-energy particulate air (HEPA)-filtered single rooms. First case was a 62 years-old man with advanced multiple myeloma, which was refractory to multiple line treatment with high dose steroid including regimens and with secondary acute myelogenous leukaemia (AML); second case was a 45 years-old male patient with multiple myeloma, who had undergone autologous HSCT following high dose chemotherapy; third case was a 52 years-old man with AML that was refractory to multiple line treatment and had undergone allogeneic HSCT from a HLA-matched unrelated donor. Nasopharyngeal aspirate samples were collected from the patients in order to search for RSV positivity. RSV was investigated by in-house nested polymerase chain reaction (PCR) in the first patient and by direct antigen detection method (Monofluoscreen RSV-Biorad, France) in the others. First case had clinical picture of RSV infection just on the HSCT day when high dose chemotherapy has already been given. As RSV-RNA analysis yielded positive result, peroral ribavirin was initiated. Engraftment did not occur in this patient. He developed severe respiratory failure which necessitated mechanical ventilatory support, however, he has succumbed. After the detection of RSV positive index case, weekly screening of RSV in other five patients in the same unit had been performed. Following the first case, after nine and 17 days, respectively, RSV positivity was detected in two more patients. While clinical signs and symptoms of RSV infection developed in second case, third case remained asymptomatic. Both of the following patients had received ribavirin very early at first RSV positivity and recovered from RSV infection. Engraftment did not occur in the last patient who had undergone allogeneic HSCT from a HLA-matched unrelated donor and a second HSCT was performed. As a result, in HSCT patients, early diagnosis of RSV infection by PCR analysis may provide support to postpone immunosupressive treatment and help assesment of the management.

Haemophagocytosis in a patient with Crimean Congo haemorrhagic fever.

Crimean-Congo haemorrhagic fever (CCHF) is a severe disease with a case fatality of 2.8 to 80 %. A patient dwelling in an endemic region for CCHF was admitted with fever preceding bleeding diathesis and pancytopenia. Despite no history of tick exposure, CCHF was highly suspected. With an oral ribavirin therapy, clinical and laboratory improvements were obtained. The diagnosis was confirmed by detection of IgM antibody to CCHF virus and positive RT-PCR. Although the main pathogenesis of CCHF infection is not elucidated yet, haemophagocytosis, a symptom rarely reported in viral haemorrhagic fevers, was observed in this case. Haemophagocytosis is suggested to have a role in the development of pancytopenia in CCHF, the mechanism of which still needs to be investigated, probably with cytokine studies. Together with clinical symptoms and patient history, haemophagocytosis may be an indicator for CCHF.

Multiple sclerosis-like clinical and magnetic resonance imaging findings in human immunodeficiency virus positive-case.

OBJECTIVE: Neurologic complications may develop during the course of acquired immunodeficiency syndrome. Differential diagnosis of the chronic progressive myelopathy related to human immunodeficiency virus must include multiple sclerosis. CASE REPORT: We report a human immunodeficiency virus-positive case with progressive myelopathy who showed multiple sclerosis-like white matter lesions on cranial magnetic resonance imaging. Viral screening revealed positive serology for human immunodeficiency virus. CONCLUSION: This case suggests that in a patient who presents with a multiple sclerosis-like clinical course and cerebral white matter lesions, a human immunodeficiency virus-related clinical picture should be taken into consideration in the differential diagnosis.

Risk factors for mortality of nosocomial bacteraemia in intensive care units.

OBJECTIVE: The aim of this study was to follow critically ill patients prospectively in intensive care units (ICUs) to determine risk factors for mortality and outcome associated with nosocomial bacteraemia (NB). SUBJECTS AND METHODS: A case-control study of 176 patients was conducted to identify the risk factors for mortality of NB in ICU patients. The study was performed in emergency, surgical and general surgical ICUs with 23 beds during a 15-month period. A total of 1,450 patients were admitted to the ICUs during the study period. The USA Center for Disease Control and Prevention definitions were used to diagnose nosocomial infections. Nosocomial bacteraemia was defined as the isolation of one or more organisms from blood cultures taken at least 48 h after admission, which were not related to a problem present on admission. An assessment of whether the isolated organisms represented true bacteraemia rather than contamination was made by clinical or laboratory evidence of infection. RESULTS: A total of 214 bacteraemia episodes were found in the 176 patients (64 female, 112 male; 51.3 +/- 21.3 years old), 90 of whom died and 86 survived. The bacteraemia rate was 12.1%. The most common etiological agents of bacteraemia were Klebsiella pneumoniae: 46 (21.5%), methicillin-resistant Staphylococcus aureus: 46 (21.5%), Pseudomonas aeruginosa: 32 (14.9%), and Escherichia coli: 20 (9.3%). Multivariate analysis showed that the requirement of mechanical ventilation for more than 7 days (p < 0.001), total parenteral nutrition (p = 0.034), inotropic drug (p < 0.001), and increased creatinine level (p = 0.034) were independent risk factors for mortality of NB in ICUs. CONCLUSIONS: Nosocomial infections caused by Gram-negative bacteria continue to be one of the major sources of morbidity and mortality.

Ventilator-associated pneumonia in surgical emergency intensive care unit.

OBJECTIVE: To investigate the incidence, risk factors and the etiology of ventilator-associated pneumonia (VAP) in surgical emergency intensive care unit (ICU) patients. METHODS: We conducted this prospective cohort study in the surgical emergency ICU of Istanbul Medical Faculty between December 1999 and May 2001. We included 100 mechanically ventilated patients in this study. We diagnosed VAP according to the current diagnostic criteria. We identified the etiology of VAP cases by both quantitative cultures of endotracheal aspiration and blood cultures. To analyze the predisposing factors for the development of VAP, we recorded the following variables: age, gender, acute physiology and chronic health evaluation (APACHE) II score, Glasgow coma scale (GCS), sequential organ failure assessment (SOFA) score, serum albumin level, duration of mechanical ventilation (MV) prior to the development of VAP, and underlying diseases. RESULTS: We determined the VAP incidence rate as 28%. We found the APACHE II score and the duration of MV to be statistically significant variables for the development of VAP. There were no significant differences regarding age, gender, GCS, SOFA score, albumin level, or underlying diseases for the development of VAP. The isolated bacteria among VAP cases were as follows: Staphylococcus aureus (n=12, 43%), Acinetobacter spp. (n=6, 21%), coagulase-negative Staphylococci (n=4, 15%), Pseudomonas aeruginosa (n=3, 10.7%) and Klebsiella pneumoniae (n=3, 10.7%). CONCLUSION: Ventilator-associated pneumonia is a common infection, and certain interventions might affect the incidence of VAP. The ICU clinicians should be aware of the risk factors for VAP, which could prove useful in identifying patients at high risk for VAP, and modifying patient care to minimize the risk of VAP.

Idiopathic necrotizing fasciitis: risk factors and strategies for management.

The prognosis of necrotizing fasciitis (NF) depends on early diagnosis and management. Idiopathic NF may be more challenging, because it occurs in the absence of a known causative factor. Therefore, our purpose in this study was to identify the distinct features of idiopathic NF that may be important in early recognition of this disease and determine the factors associated with mortality. A retrospective chart review was performed in patients with a diagnosis of NF between 1988 and 2003. Patients were classified as idiopathic and secondary NF, and data were analyzed in terms of etiological and predisposing factors, causative microbiological organisms, and clinical outcome. The study included 98 patients, 63 men and 35 women, with a diagnosis of NF. The median age was 55.5 years (range, 13 - 80). Idiopathic NF occurred in 60 of 98 patients (61%). The principal anatomic sites of infection for NF were perineal localisation in 55 patients (66%) and extremities in 31 patients (32%). Characteristics that distinguish patients with idiopathic NF from secondary NF were as follows: age older than 55 years (P = 0.0001), presence of comorbid illnesses like DM (P = 0.007) or chronic renal failure (P = 0.041), and perineal localization (P = 0.008). By logistic regression analysis, independent risk factors for idiopathic NF remained age > 55 years and perineal localization as statistically significant factors, when all the significant variables found in univariate analysis were included in the model. The majority of patients (82%) had polymicrobial infections. The mortality rate was 35 per cent. All patients were treated with radical surgical debridement and a combination of antibiotics. Female gender, presence of malignant disease, and diabetes mellitus (DM) were found to be associated with increased mortality as independent factors in logistic regression analysis, when all of these three factors were included in the model. Understanding the distinct clinical characteristics and the factors associated with mortality in patients with NF may lead to rapid diagnosis and improve the survival rates. Therefore, idiopathic NF is a crucial entity that requires serious suspicion for its diagnosis.

Endoscopic and radiologic interventions as the leading causes of severe cholangitis in a tertiary referral center.

BACKGROUND: Iatrogenic factors became the leading mechanisms of severe cholangitis in a referral center. PATIENTS AND METHODS: The records of the 58 patients treated for severe cholangitis between 1996 and May 2004 (inclusive) were evaluated. RESULTS: The most frequent underlying diseases were periampullary tumors and mid-bile duct carcinomas (22), followed by proximal cholangiocarcinomas (14). The triggering mechanism was an incomplete endoscopic retrograde cholangiopancreatography (ERCP) in 32 patients, incomplete or inappropriate percutaneous transhepatic biliary drainage (PTBD) in 6, apparently successful ERCP and stenting in 1, and percutaneous transhepatic cholangiography in 1. PTBD was the treatment of choice (38). Mortality was 29% (17/58); the major causes were refractory sepsis (8) and incomplete biliary drainage (advanced tumor, technical failure, or hemobilia) (8). CONCLUSIONS: In this series composed predominantly of patients referred after development of sepsis, ERCP and PTBD complications were the leading mechanisms of severe cholangitis. Nonoperative biliary manipulations are invasive procedures with potentially fatal complications. The decisions to perform such procedures and periprocedural management are responsibilities of an experienced multidisciplinary team.

Extrapulmonary tuberculosis in immunocompetent adults.

Tuberculosis continues to be a significant cause of morbidity and mortality. Although tuberculosis usually attacks the lungs, other organs can also be affected, leading to extrapulmonary tuberculosis (EPT) or disseminated tuberculosis. This study retrospectively analysed the incidence, clinical sites and risk factors for EPT in 252 patients with EPT between 1 January 1991 and 30 June 2003. EPT was defined as clinical, laboratory, imaging, and/or histopathological evidence of mycobacterial infection in a site other than hilar lymph nodes or lung parenchyma. In our study group, tuberculous lymphadenitis (36.5%) was found to be the most common clinical presentation of EPT. 119 (47.2%) patients developed the severe form of EPT, according to the WHO report, and 133 (52.8%) patients developed the less severe form. A case history of pulmonary tuberculosis was found to be a risk factor for the development of EPT (p <0.05). The study showed that EPT is still a public health problem. These findings suggested that pulmonary tuberculosis may play a critical role in the development of EPT. 12-month therapy may be chosen in patients with EPT considering acceptable adverse effects without relapses.

Central venous catheter related infections: risk factors and the effect of glycopeptide antibiotics.

BACKGROUND: We undertook a prospective study of all new central venous catheters inserted into patients in the intensive care units, in order to identify the risk factors and to determine the effect of glycopeptide antibiotics on catheter - related infections. METHODS: During the study period 300 patients with central venous catheters were prospectively studied. The catheters used were nontunneled, noncuffed, triple lumen and made of polyurethane material. Catheters were cultured by semiquantitative method and blood cultures done when indicated. Data were obtained on patient age, gender, unit, primary diagnosis on admission, catheter insertion site, duration of catheterization, whether it was the first or a subsequent catheter and glycopeptide antibiotic usage. RESULTS: Ninety-one (30.3%) of the catheters were colonized and infection was found with 50 (16.7%) catheters. Infection was diagnosed with higher rate in catheters inserted via jugular vein in comparison with subclavian vein (95% CI: 1.32-4.81, p = 0.005). The incidence of infection was higher in catheters which were kept in place for more than seven days (95% CI 1.05-3.87, p = 0.03). The incidence of infection was lower in patients who were using glycopeptide antibiotic during catheterization (95% CI: 1.49-5.51, p = 0.005). The rate of infection with Gram positive cocci was significantly lower in glycopeptide antibiotic using patients (p = 0.01). The most commonly isolated organism was Staphylococcus aureus (n = 52, 37.1%). CONCLUSION: Duration of catheterization and catheter insertion site were independent risk factors for catheter related infection. Use of glycopeptide antibiotic during catheterization seems to have protective effect against catheter related infection.