Carbapenem-Resistant Klebsiella pneumoniae Among Patients with Ventilator-Associated Pneumonia: Evaluation of Antibiotic Combinations and Susceptibility to New Antibiotics.

Background: Carbapenemase-producing Gram-negative bacteria, particularly Klebsiella pneumoniae (K. pneumoniae), are at the forefront of the list of causative agents of ventilator-associated pneumonia (VAP). The treatment options for such infections are limited, and various antimicrobial combinations have been suggested as alternatives in clinical practice. New antibiotics, such as ceftazidime/avibactam, ceftolozane/tazobactam and cefiderocol, have shown advantages in both in vitro and clinical studies. Purpose: To evaluate the in vitro effect of meropenem-ciprofloxacin and meropenem-colistin combinations on carbapenem-resistant (CR) K. pneumoniae VAP isolates and to determine their susceptibility to new antibiotics. Methods: Seventy-three K. pneumoniae isolates from 176 endotracheal samples from VAP cases were studied. Antibiotic susceptibility testing and phenotypic detection of extended-spectrum ß lactamase (ESBL) and carbapenemase production were done. CR K. pneumoniae isolates were tested for the five predominant carbapenemase genes (bla KPC, bla OXA-48, bla NDM, bla VIM, and bla IMP). In vitro evaluation of meropenem-ciprofloxacin and meropenem-colistin combinations was done by MIC test strips. Susceptibility to new antibiotics was tested by disk diffusion method. Results: Sixty-three (86.3%) of the isolates were ESBL producers and 52 (71.2%) were carbapenem resistant. Bla NDM was the most prevalent carbapenemase gene (50%), followed by bla OXA-48, (36.5%) then bla KPC in (11.5%). Bla VIM and bla IMP were not detected. Meropenem-ciprofloxacin combination showed indifferent effect on all isolates, while meropenem-colistin combination showed 25% synergism, 15.4% addition and 59.6% indifference. All (100%) CR K. pneumoniae isolates were resistant to ceftolozane/tazobactam and 79% were resistant to ceftazidime/avibactam, while 96% were sensitive to cefiderocol. Conclusion: A high rate of carbapenem resistance exists among VAP K. pneumoniae isolates. Meropenem-colistin combination and cefiderocol appear to be potential treatment options for infections caused by CR K. pneumoniae. Resistance to the tested new ß-lactam/ß-lactamase inhibitors was high, signifying a major threat.

A comparative study on nosocomial and community-acquired spontaneous bacterial peritonitis in patients with liver cirrhosis at a university hospital.

BACKGROUND: The serious nature of spontaneous bacterial peritonitis (SBP) in patients with cirrhosis and the need for timely effective empirical antibiotic therapy in the context of the global surge of antimicrobial resistance and changing epidemiology necessitate a periodic review of the local epidemiologic features of the disease. AIM: The aim of the study is to investigate the differences in bacterial profile and antibiotic resistance between nosocomial and community-acquired SBP in patients with liver cirrhosis to guide empirical antibiotic choices for better outcomes. METHODS: This cross-sectional study included 95 ascitic cirrhotic patients diagnosed with SBP. According to the setting in which the infection was acquired, the patients were divided into two groups: nosocomial and community-acquired SBP. The bacterial profile and rates of multidrug resistance (MDR) phenotype and the extended-spectrum ß-lactamase (ESBL) production among Gram-negative isolates in both groups were compared. RESULTS: Escherichia coli was the most frequently isolated bacteria (60% of all isolates) followed by Klebsiella pneumoniae (11.4%). Gram-positive bacteria were only isolated from nosocomial SBP cases; the most common was Staphylococcus aureus (11.4%) followed by coagulase-negative staphylococci (5.7%). High rates of resistance to third-generation cephalosporins, the first-line empirical treatment of SBP, were detected (76.6-100% in nosocomial isolates and 25-87% in community isolates). Carbapenems, amikacin and gentamycin showed good activity against Gram-negative bacilli in both nosocomial and community-acquired isolates. MDR bacteria, including ESBL-producing Enterobacteriaceae, were significantly associated with nosocomial SBP. CONCLUSION: The significant increase in MDR phenotype and ESBL production among nosocomial isolates necessitates a change in the initial empirical therapy for nosocomial SBP and carbapenems seem good alternatives.

Forkhead Box P3 (Foxp3) serum level and Foxp3 Gene-Promoter polymorphisms in Egyptian rheumatoid arthritis patients: A case-control study.

Regulatory T (Treg) cells are the chief player in induction of autotolerance and the transcription factor, Forkhead Box P3 (Foxp3), is the master regulator of their development and function. Polymorphisms in Foxp3 locus affect Foxp3 expression and can influence Treg cell function. This study aimed to determine the frequency of -3279C/A and -924A/G polymorphisms in the promoter region of the Foxp3 gene in Egyptian rheumatoid arthritis (RA) patients in comparison to apparently healthy controls, to test their association with Foxp3 serum levels as well as with patients' clinical and laboratory features. Also, to evaluate Foxp3 serum level as a putative measure of Foxp3+ Treg cells-mediated immune regulation and disease activity. A total of 136 subjects (68 RA patients and 68 controls) were studied for determining the frequency of both -3279 C/A and -924 A/G polymorphisms in the Foxp3 promoter region by PCR-RFLP and measuring their Foxp3 protein serum levels by ELISA. Our results indicated that; -3279 Foxp3 CA and AA genotypes were significantly higher in patients than controls (OR (95% CI) = 2.86 (1.31-6.26) and 2.79 (1.11-7.07), P= 0.008 and p = 0.03, respectively). Similarly, -924 AG genotype was significantly higher in patients than controls (OR (95% CI) = 2.92 (1.35-6.34); P=0.006). A significantly higher risk of RA was associated with the Foxp3 polymorphic variants -3279 A and -924 G. There was a statistically significant elevation in Foxp3 serum levels among patients, which was positively correlated to disease activity score and disease grade. In conclusion, Foxp3 polymorphisms influenced the risk of developing RA, but did not influence disease severity or activity. Serum level of Foxp3 is not a reliable indicator of Treg-mediated immune regulation in RA patients.

Community acquired pneumonia among adult patients at an Egyptian university hospital: bacterial etiology, susceptibility profile and evaluation of the response to initial empiric antibiotic therapy.

BACKGROUND: Effective empirical antibiotic therapy for community acquired pneumonia (CAP), based on frequently updated data about the pattern of bacterial distribution and their antimicrobial susceptibilities, is mandatory. AIM: To identify the bacterial etiology of CAP in adults and their antibiotic susceptibility patterns and to evaluate the response to initial empirical antibiotic therapy in an Egyptian university hospital. SETTINGS AND DESIGN: A cross-sectional hospital-based study. PATIENTS AND METHODS: CAP cases were selected by systemic random sampling from those admitted to the chest department. All were evaluated at admission and 4 days after starting empiric therapy. Typical bacteria were isolated, identified and tested for their antibiotic susceptibility. An indirect IF assay was used to diagnose atypical bacteria. Clinical response to initial empiric antibiotic therapy was clinically, laboratory and radiologically evaluated. RESULTS: Two hundred and seventy CAP patients were included. Bacteria represented 50.4% of them. Klebsiella pneumoniae was the most prevalent bacterium (10.37%) followed by Streptococcus pneumoniae and P. aeruginosa (7.78% each). Overall, 76.2% of isolates showed a multidrug resistant phenotype: 82.61% (19/23) S. pneumoniae, 89.66 % (26/29) K. pneumoniae, 65.22% (15/23) Pseudomonas aeruginosa, 87.50% (7/8) Escherichia coli and 81.25 % (13/16) Staphylococcus aureus. Broad spectrum ß-lactams, especially carbapenems, and moxifloxacin showed in vitro efficacy on most of the tested isolates. Forty-three cases (15.9%) were nonresponders, 37 (86%) of them showed bacterial etiology. The highest rate of nonresponsiveness (30.43%) was observed in cases receiving antipseudomonal/antipneumococcal ß-lactam plus a fluoroquinolone for suspected P. aeruginosa infection. CONCLUSION: Multidrug resistance in bacteria causing CAP and high frequency of isolation of hospital pathogens are prominent features of this study. Azithromycin containing regimens were associated with the lowest rates of nonresponsiveness. Development and implementation of an antibiotic stewardship program are highly recommended for CAP management.

Carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa: characterization of carbapenemase genes and E-test evaluation of colistin-based combinations.

BACKGROUND: Carbapenamase producing Acinetobacter baumannii and Pseudomonas aeruginosa are emerging worldwide limiting the use of carbapenems as effective and safe drugs. PURPOSE: To characterize different carbapenemase genes carried by carbapenem-resistant (CR) A. baumannii and P. aeruginosa isolates and to evaluate the in vitro effect of some colistin-based combinations by E-test method in Zagazig University Hospitals ICU isolates. METHODS: CR A. baumannii and P. aeruginosa isolated from the surgical intensive care unit (ICU) were tested for carbapenemase genes by polymerase chain reaction and the effect of colistin/meropenem and colistin/tigecycline combinations was evaluated by E-test. RESULTS: Genes coding for OXA-23, NDM and GES were detected in 90, 66.7 and 50% of CR A. baumannii, respectively, while genes coding for VIM, GES, NDM and IMP were detected in 50, 40.9, 27.3 and 18.2% of CR P. aeruginosa, respectively. Colistin/tigecycline combination showed synergistic and additive effect in 20% and 60% of A. baumannii isolates, respectively, while colistin/meropenem combination showed synergistic and additive effect in 63.6% and 36.4% of P. aeruginosa, respectively. CONCLUSION: Carbapenemase genes carriage accounts for high level carbapenem resistance in our isolates. Colistin/tigecycline and colistin/meropenem combinations can be considered for treatment of severe infections by CR A. baumannii and P. aeruginosa, respectively.

T Regulatory Cells Response to Allergen Specific Immunotherapy in Patients with Allergic Airway Diseases: A Prospective Study.

Forkhead box P3 (FoxP3) T regulatory (Treg) cells modulate the immune system by blocking other types of T-cells. They maintain tolerance to self-antigens and help in inducing tolerance to foreign antigens. A deregulation of FoxP3 Tregs seems to play an important role in allergic disorders. The aim of this work was to study the response of FoxP3 Treg cells and their FoxP3 expression in patients, attending the Allergy Unit and the Chest Outpatient Clinic, Faculty of Medicine, Zagazig University, with allergic airway diseases, before and 1 year after receiving subcutaneous allergen specific immunotherapy (SIT). This prospective study was carried out on 25 patients with allergic airway diseases, confirmed by positive skin test, and that showed clinical improvement one year after SIT. All cases were subjected to total immunoglobulin E quantitation by ELISA. FoxP3 Treg cells frequency and FoxP3 relative fluorescence intensity, as an indicator of Tregs function, were assessed by flowcytometry. The results were compared before and after SIT. Twenty five age and sex matched apparently healthy volunteers were enrolled as controls. Our findings demonstrated that in comparison to the control group, the count of FoxP3 T regulatory cells was higher; however, the function was lower among the enrolled patients (P= 0.007 and P< 0.001, respectively). When FoxP3 Tregs were compared in the patients before and one year after SIT, it was found that both the count and FoxP3 expression showed statistically significant increase (P< 0.001). An inverse correlation was found between FoxP3 Tregs count and FoxP3 expression. It is concluded that patients with allergic airway diseases have increased number of FoxP3 Treg cells but with defective function. SIT plays a role in increasing the number of FoxP3 Tregs and improving their suppressive function, which leads to control of airway inflammation and thus clinical improvement.