Changing patterns of bacterial profile and antimicrobial resistance in high-risk patients during the COVID-19 pandemic at a tertiary oncology hospital.

The widespread evolution of phenotypic resistance in clinical isolates over the years, coupled with the COVID-19 pandemic onset, has exacerbated the global challenge of antimicrobial resistance. This study aimed to explore changes in bacterial infection patterns and antimicrobial resistance during the COVID-19 pandemic. This study involved the periods before and during COVID-19: the pre-pandemic and pandemic eras. The surveillance results of bacterial isolates causing infections in cancer patients at an Egyptian tertiary oncology hospital were retrieved. The Vitek®2 or Phoenix systems were utilized for species identification and susceptibility testing. Statistical analyses were performed comparing microbiological trends before and during the pandemic. Out of 2856 bacterial isolates, Gram-negative bacteria (GNB) predominated (69.7%), and Gram-positive bacteria (GPB) comprised 30.3% of isolates. No significant change was found in GNB prevalence during the pandemic (P = 0.159). Elevated rates of Klebsiella and Pseudomonas species were demonstrated during the pandemic, as was a decrease in E. coli and Acinetobacter species (P < 0.001, 0.018, < 0.001, and 0.046, respectively) in hematological patients. In surgical patients, Enterobacteriaceae significantly increased (P = 0.012), while non-fermenters significantly decreased (P = 0.007). GPB species from either hematological or surgical wards exhibited no notable changes during the pandemic. GNB resistance increased in hematological patients to carbapenems, amikacin, and tigecycline and decreased in surgical patients to amikacin and cefoxitin (P < 0.001, 0.010, < 0.001, < 0.001, and 0.016, respectively). The study highlights notable shifts in the microbial landscape during the COVID-19 pandemic, particularly in the prevalence and resistance patterns of GNB in hematological and surgical wards.

The impact of increasing non-albicans Candida trends on diagnostics in immunocompromised patients.

Invasive candidiasis (IC) represents a growing concern worldwide, with a considerable increase in non-albicans Candida (NAC) species. The study's primary goal was to determine if species identification by semi-nested PCR (sn-PCR) with primers for the five most prevalent Candida species is sufficient to deal with the current trends of Candida infections in cancer patients. Over one year, Candida isolates were collected from samples of patients with hematological and solid organ tumors in a single center. Species of Candida were identified by chromagar and multiplex sn-PCR using specific primers for Candida albicans, Candida tropicalis, Candida glabrata, Candida krusei, and the Candida parapsilosis complex. Most Candida infection episodes are caused by NAC species (70.5% of 105 isolates). Rare species (14 isolates) accounted for 13.3% of isolates and were not identified by sn-PCR using the five most common Candida species primers. More than half of these rare species caused candidemia in cancer patients (57.1%; p = 0.011). The risk factor for candidiasis was recent surgeries (p = 0.020) in adults and chemotherapy in pediatric patients (p = 0.006). Prolonged hospitalization and genitourinary tract cancer were significantly associated with invasive infections (p = 0.005 and 0.049, respectively). Recent surgery was a significant risk factor associated with C. parapsilosis and C. glabrata infections (P = 0.038 and 0.003, respectively), while C. tropicalis was significantly more common in patients with hematological malignancies (P = 0.012). Techniques with a broader identification spectrum than the major five Candida species are crucial for the optimal management of cancer patients.

Alarming Increase of Azole-Resistant Candida Causing Blood Stream Infections in Oncology Patients in Egypt.

Candidemia is a life-threatening invasive fungal infection in immunocompromised patients. The widespread use of azoles and the shift toward non-albicans Candida (NAC) species remarkably increase azole resistance in developing countries. We aimed to study candidemia trends and associated risk factors in oncology patients since they vary geographically, and rapid and appropriate treatment improves outcomes. Vitek 2 was used to identify the Candida species, and the E-test determined their susceptibility to azoles. Candida was the cause of 3.1% (n = 53/1701) of bloodstream infections (BSIs) during a 1-year study. Candida tropicalis was the most predominant species among the 30 candidemia episodes studied (36.7%), followed by C. albicans (33.3%). However, C. krusei, C. guilliermondii, C. pelliculosa, C. parapsilosis, C. famata, and C. inconspicua accounted for 30.0% of the isolates. An increased risk of NAC BSI was significantly associated with chemotherapy and leucopenia (P = 0.036 and 0.016, respectively). However, the multivariable analysis revealed that leucopenia was the only independent risk factor (P = 0.048). Fluconazole and voriconazole resistance were 58.3% and 16.7%, with NAC species showing higher resistance rates than C. albicans. Both fluconazole and voriconazole minimum inhibitory concentration (MIC) median values were higher in NAC than in C. albicans, but only voriconazole was significantly higher (0.220 versus 0.048 µg/ml, P = 0.047). In conclusion, the increased prevalence of NAC BSIs and incredibly high fluconazole resistance rates in cancer patients emphasize the necessity of antifungal stewardship to preserve voriconazole effectiveness, continued surveillance of candidemia, and future studies into azole resistance molecular mechanisms.

Impact of Rapid Molecular Diagnostic Technique on Time to Optimal Antimicrobial Therapy and Hospital Outcomes in Pediatric Cancer Patients with Sepsis.

BACKGROUND: sepsis is a leading cause of morbidity and mortality in pediatric cancer patients. We sought to assess the impact of using rapid molecular diagnostic techniques on time to pathogen identification, early administration of targeted antimicrobial treatment, and hospital outcomes. PATIENTS AND METHODS: This prospective study was conducted at the Egyptian National Cancer Institute (1/2018-1/2019) on pediatric cancer patients with suspected sepsis. The cohort was divided into two groups. In one group, blood samples were sent for rapid molecular detection [multiplex-Polymerase Chain Reaction (PCR)] and blood cultures (PCR-group). While only blood cultures were collected for the second group (BC-group). RESULTS: In the entire cohort (n=120), the most common bacteria identified on blood cultures was Escherichia Coli (n=33,27.5%) followed by Klebsiella (n=31,25.8%). Multidrug-resistant bacteria were identified in 63 patients (52.5%). The median turnaround time to initial results was 5 hours in PCR-group (n=60), and 120 hours in BC-group (n=60)(P<0.001). For PCR-group, agreement in pathogen identification between the rapid molecular detection kit (PCR) and blood cultures was noted in 56 patients (93.3%). While the remaining four patients had no bacterial growth on blood cultures. The empirical antibiotic treatment for the PCR-group was modified based on the result of the PCR test. Antibiotic shift, based on blood culture sensitivity results, was done in 29 patients (48%) in PCR-group, compared to 45 patients (75%) in BC-group (P=0.003). Median sepsis episode duration [8-days vs. 10-days,P=0.361), and hospital mortality (42% vs. 50%, P=0.360) were slightly lower in PCR-group. However, this did not reach statistical significance. CONCLUSION: There was a substantial agreement in pathogen identification between the rapid molecular detection method (PCR) and blood culture results. PCR had a much shorter turnaround time, which allows for earlier start of optimal antimicrobial treatment, and might potentially improve hospital outcomes, which in turn will reduce associated health care costs.

Increasing trends of colistin resistance in patients at high-risk of carbapenem-resistant Enterobacteriaceae.

INTRODUCTION: Occurrence of colistin-resistant Enterobacteriaceae in response to the unregulated use of this antibiotic has been documented. This study reports an investigation of colistin resistance rates among carbapenem-resistant enterobacterial clinical isolates. METHODS: A total of 196 multidrug-resistant Enterobacteriaceae isolates (Klebsiella pneumoniae (n = 100), Escherichia coli (n = 89) and Enterobacter cloacae (n = 7) were selected from Gram-negative isolates over one year. Susceptibility to antimicrobials was determined using Vitek2. Broth microdilution method was used to detect colistin antimicrobial susceptibility. Identification of ESBL and carbapenemases were both done phenotypically and by PCR. RESULTS: All the studied isolates showed multidrug-resistant phenotypes with 51.5% resistance to carbapenems (meropenem, imipenem). Very low resistance rates towards tigecycline (n = 9) 4.6% were found. Thirty-nine isolates (19.9%) showed reduced susceptibility to colistin among the MDR isolates. Sixty-four isolates (32.7%) were ESBL producers. Hundred isolates (51%) were carbapenemase producers using Carba NP test. The PCR amplification results revealed that 40 isolates (20%) harboured NDM-1 and 40 isolates contained OXA-48-like gene. Coexistence of both (NDM-1 and OXA-48-like) was observed in nine (4.59%) isolates. A Statistically significant relationship was observed between carbapenem resistance and each of the followings; OXA-48 producers (p= .009), amikacin resistance (p = .000), gentamicin resistance (p = .032), tobramycin resistance (p = .000), and tigecycline resistance (p-value ≤ .001). A statistical significance was detected between ESBL-producing isolates and carbapenem susceptible isolates ESBL producers with p = 0.000. CONCLUSION: An alarming sign is the increasing colistin resistance rates among carbapenem-resistant isolates. Aminoglycosides are still a therapeutic option to decrease the use of colistin and avoid further development of resistance.KEY MESSAGESHigh rates of colistin resistance among carbapenem-resistant Enterobacteriaceae.The choice of antibiotic is significantly associated with the clinical site of infection.Aminoglycosides are offered choices for treating multiple drug-resistant Enterobacteriaceae to preserve the colistin and carbapenems.

Landscape of Multidrug-Resistant Gram-Negative Infections in Egypt: Survey and Literature Review.

PURPOSE: This article is the first to review published reports on the prevalence of multidrug-resistant (MDR) gram-negative infections in Egypt and gain insights into antimicrobial resistance (AMR) surveillance and susceptibility testing capabilities of Egyptian medical centers. MATERIALS AND METHODS: A literature review and online survey were conducted. RESULTS: The online survey and literature review reported high prevalence of extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae (19-85.24% of E. coli, and 10-87% of K. pneumoniae), carbapenem-resistant Enterobacteriaceae (35-100% of K. pneumoniae and 13.8-100% of E. coli), carbapenem-resistant Acinetobacter baumannii (10-100%), and carbapenem-resistant Pseudomonas aeruginosa (15-70%) in Egypt. Risk factors for MDR Gram-negative infections were ventilated patients (67.4%), prolonged hospitalization (53.5%) and chronic disease (34.9%). Although antimicrobial surveillance capabilities were deemed at least moderate in most centers, lack of access to rapid AMR diagnostics, lack of use of local epidemiological data in treatment decision-making, lack of antimicrobial stewardship (AMS) programs, and lack of risk prediction tools were commonly reported by respondents. CONCLUSION: This survey has highlighted the presence of knowledge gaps as well as limitations in the surveillance and monitoring capabilities of AMR in Egypt, with most laboratories lacking rapid diagnostics and molecular testing. Future efforts in Egypt should focus on tackling these issues via nationwide initiatives, including understanding the AMR trends in the country, capacity building of laboratories and their staff to correctly and timely identify AMR, and introducing newer antimicrobials for targeting emerging resistance mechanisms in Gram-negative species.

Severe COVID-19 and Sepsis: Immune Pathogenesis and Laboratory Markers.

The ongoing outbreak of the novel coronavirus disease 2019 (COVID-19), induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has taken a significant toll on people and countries all over the world. The pathogenesis of COVID-19 has not been completely elucidated yet. This includes the interplay between inflammation and coagulation which needs further investigation. The massive production of proinflammatory cytokines and chemokines results in the so-called cytokine storm, leading to plasma leakage, vascular hyperpermeability, and disseminated vascular coagulation. This is usually accompanied by multiorgan failure. The extensive changes in the serum levels of cytokines are thought to play a crucial role in the COVID-19 pathogenesis. Additionally, the viral load and host inflammation factors are believed to have a significant role in host damage, particularly lung damage, from SARS-CoV-2. Interestingly, patients exhibit quantitative and qualitative differences in their immune responses to the virus, which can impact the clinical manifestation and outcomes of COVID-19. There needs to be a better understanding of the dynamic events that involve immune responses, inflammatory reactions, and viral replication in the context of the COVID-19 infection. Here, we discuss the main aspects of COVID-19 pathogenesis while supporting the hypothesis that inflammatory immune responses are involved in the progression of the disease to a more critical and fatal phase. We also explore the similarities and differences between severe COVID-19 and sepsis. A deeper understanding of the COVID-19 clinical picture as it relates to better-known conditions such as sepsis can provide useful clues for the management, prevention, and therapy of the disease.

Emergence of colistin resistance in multidrug-resistant Klebsiella pneumoniae and Escherichia coli strains isolated from cancer patients.

BACKGROUND: Colistin resistance is mainly driven by alterations in the Gram-negative outer membrane lipopolysaccharides and is caused, in most cases, by mutations in mgrB gene. However, the recent emergence of plasmid-encoded colistin resistance among Enterobacteriaceae strains represents a serious threat to global public health. In this paper we have investigated the rates of colistin resistance and the underlying mechanisms in 450 Klebsiella pneumoniae and Escherichia coli isolates obtained from cancer patients in Egypt. METHODS: Colistin susceptibility and minimum inhibitory concentrations were determined according to the European Committee on Antimicrobial Susceptibility Testing, by broth microdilution, and by E-test. The mcr-1, mcr-2 and mgrB genes were detected by PCR and then sequenced. Clonal diversity in colistin-resistant K. pneumoniae was evaluated by multilocus sequence typing. RESULTS: Forty (8.8%) colistin-resistant isolates, including 22 K. pneumoniae and 18 E. coli, were isolated over 18 months. Of these, 50% were carbapenem-resistant, out of which nine were blaOXA-48 and seven blaNDM-1 positive. The mechanisms of colistin resistance could be revealed only in three of the 40 resistant strains, being represented by mcr-1 in one blaNDM-1-positive E. coli strain and in one K. pneumoniae ST11 and by mgrB mutations, detected in one K. pneumoniae isolate. None of the studied isolates harbored mcr-2. CONCLUSIONS: Our results demonstrate a high frequency of colistin resistance in enterobacterial strains isolated from cancer patients, but a low prevalence of the most well known resistance mechanisms.

Tracing the dissemination of the international clones of multidrug-resistant Acinetobacter baumannii among cancer patients in Egypt using the PCR-based open reading frame typing (POT) method.

OBJECTIVES: The aim of this study was to perform an epidemiological surveillance of multidrug-resistant (MDR) Acinetobacter baumannii genetic lineages among cancer patients in Egypt using the PCR-based open reading frame typing (POT) method. METHODS: A total of 160 MDR A. baumannii isolates were collected between January 2015 and December 2017 at a tertiary-care centre in Egypt. VITEK®2 system was used for preliminary species identification and antimicrobial susceptibility testing. The POT method was applied for confirmation of species identification and molecular epidemiological typing of the isolates. RESULTS: MDR A. baumannii isolates were classified into 15 POT types, including POT 122 (n=69), POT 69 (n=22) and other miscellaneous POT types (MPOTs) including POT 0, 8, 10, 12, 14, 40, 44, 52, 56, 93, 104, 106 and 108 (n=69). POT 122 isolates infected or colonised 61% of patients hospitalised in surgical wards and 54% of patients diagnosed with solid tumours and 51% were adults; whereas MPOT isolates infected or colonised 51% of patients hospitalised in paediatric wards and 49% of patients diagnosed with haematological malignancies and 51% were paediatric patients (P=0.007, 0.001 and 0.004, respectively). MPOT isolates were recovered from 46% of the collected blood specimens, whilst POT 122 isolates were recovered from 61% of the collected respiratory specimens (P=0.05). CONCLUSION: The current study demonstrates that the easy, low-cost POT method is convenient for rapid delineation of A. baumannii clonal diversity in a tertiary-care hospital in Egypt.

Multiple mechanisms contributing to ciprofloxacin resistance among Gram negative bacteria causing infections to cancer patients.

Fluoroquinolones have been used for prophylaxis against infections in cancer patients but their impact on the resistance mechanisms still require further investigation. To elucidate mechanisms underlying ciprofloxacin (CIP) resistance in Gram-negative pathogens causing infections to cancer patients, 169 isolates were investigated. Broth microdilution assays showed high-level CIP resistance in 89.3% of the isolates. Target site mutations were analyzed using PCR and DNA sequencing in 15 selected isolates. Of them, all had gyrA mutations (codons 83 and 87) with parC mutations (codons 80 and 84) in 93.3%. All isolates were screened for plasmid-mediated quinolone resistance (PMQR) genes and 56.8% of them were positive in this respect. Among PMQR genes, aac(6')-Ib-cr predominated (42.6%) while qnr genes were harbored by 32.5%. This comprised qnrS in 26.6% and qnrB in 6.5%. Clonality of the qnr-positive isolates using ERIC-PCR revealed that most of them were not clonal. CIP MIC reduction by CCCP, an efflux pump inhibitor, was studied and the results revealed that contribution of efflux activity was observed in 18.3% of the isolates. Furthermore, most fluoroquinolone resistance mechanisms were detected among Gram-negative isolates recovered from cancer patients. Target site mutations had the highest impact on CIP resistance as compared to PMQRs and efflux activity.

Plasmid-Mediated Quinolone Resistance in Gram-Negative Pathogens Isolated from Cancer Patients in Egypt.

Fluoroquinolones (FQs) are the drugs of choice for prophylaxis of bacterial infections in immunocompromised cancer patients. This study aimed to investigate FQ resistance and the prevalence of plasmid-mediated quinolone resistance (PMQR) determinants in 239 Gram-negative isolates collected at a tertiary care cancer hospital in Cairo, Egypt. Disc diffusion and broth microdilution tests showed that 70.7% of the isolates were nonsusceptible to ciprofloxacin (MIC50 = 64 µg/ml). Polymerase chain reaction (PCR) revealed that 53.6% of the isolates carried at least one PMQR determinant, of which 23.4% were susceptible to ciprofloxacin. The most prevalent gene, aac(6')-Ib-cr, was identified in 36.8% of the isolates, while qnr genes were harbored by 31.0% (qnrS, 24.3%; qnrB, 7.1%, and qnrA, 0.4%). The oqxAB genes were only detected in Klebsiella sp. isolates (92.5%). PMQR determinants were more likely detectable among isolates recovered from pediatric patients than adults (59.3% vs. 43.8%) and were significantly associated with ceftriaxone and gentamicin resistance. A combined genetic analysis using random amplified polymorphic DNA-PCR and enterobacterial repetitive intergenic consensus-PCR showed that most of the qnr-positive isolates were not clonal. Findings of the current study raised concerns about the efficacy of prophylactic use of FQs in cancer patients in our region. It also demonstrates the possible role of PMQR-positive ciprofloxacin-susceptible isolates in the dissemination of resistance to other antimicrobial agents and the urgent need to reconsider the existing FQ breakpoints defined by the Clinical and Laboratory Standards Institute.

Bacteremia due to ESKAPE pathogens: An emerging problem in cancer patients.

BACKGROUND AND AIM: In recent years, a few of the antibiotic-resistant bacteria, known as ESKAPE pathogens, have been found responsible for serious infections. We investigated the risk factors, and impact of ESKAPE pathogens on course of blood stream infections (BSIs) in cancer patients in comparison to coagulase negative Staphylococci (CoNS). PATIENTS AND METHODS: The data of patients with ESKAPE positive blood cultures at National Cancer Institute, Cairo University were analyzed. Identification and antimicrobial susceptibility of isolates were done using Microscan Walk Away 96. RESULTS: In a 6month period, ESKAPE pathogens were isolated from non-duplicate blood cultures in 81 episodes of 72 cases of pediatric cancer patients, while CoNS were isolated from 135 blood cultures of 116 patients. The ESKAPE pathogens isolated were Enterobacter spp., methicillin-resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterococci in 12%, 23%, 37%, 10%, 9%, and 9% of episodes, respectively. Health-care acquired infections constituted 75% of ESKAPE infections. Duration of episodes and overall mortality were significantly higher in ESKAPE BSIs when compared to CoNS (14.5±7.6 versus 09.9±6.9), and (26% versus 4%); respectively, p value <0.001. CONCLUSIONS: ESKAPE pathogens were significantly associated with higher rates of morbidity and mortality indicating the need for improving the means of prevention of these types of infections within health care premises. Microbiology laboratories have a role in defining more dangerous infections and rapid diagnostics are required in the era of resistance.

Investigation and Management of a Rhizomucor Outbreak in a Pediatric Cancer Hospital in Egypt.

We describe an outbreak of mucormycosis in a pediatric oncology hospital during December 2010 and the measures taken to stop it. The outbreak began with two consecutive cases of laboratory-documented mucormycosis infections within 1 week. Investigations to track the source were conducted immediately. Air plate cultures from machines and ducts supplying patients' rooms revealed the growth of Rhizomucor. Of five affected patients, all had acute leukemia and three were histopathologically proven. All patients were treated with liposomal amphotericin B after mucormycosis was diagnosed. Posaconazole was used as a secondary prophylaxis in one case. Three patients died.

Increasing Antimicrobial Resistance Monitored in Surveillance Analysis of Blood Stream Infections in Febrile Neutropenic Pediatric Oncology Patients.

BACKGROUND: Continuous surveillance of pattern of blood stream infection is necessary in febrile neutropenia (FN)especially with the recent escalating trend in the management of pediatric cancer patients towards intensified regimens and with the increase in infections caused by resistant organisms limiting the choice of antibiotics. AIM: To monitor change in pattern of blood stream infections (BSI) in FN pediatric cancer patients. MATERIALS AND METHODS: Surveillance of FN episodes with positive BSI was prospectively monitored and compared to a previous surveillance in the same pediatric oncology unit. RESULTS: A total of 232 BSI positive episodes were documented in 192 patients during a 6 months period. The results of recent surveillance analysis showed an increase in intensified regimens of chemotherapy, antimicrobial resistance, fungal infections, and prolonged duration of episodes when compared to previous surveillance, with p value sof <0.001, 0.005, 0.021, and <0.001, respectively. There was an apparent decrease in the crude mortality but this was not statistically significant, to 6% in 2011 from 10 % in 2006. CONCLUSIONS: The pattern of BSI at our institution is still inclining towards gram positive organisms but is showing a shift towards more antibiotic resistance and fungal infections.

Antimicrobial resistance pattern and their beta-lactamase encoding genes among Pseudomonas aeruginosa strains isolated from cancer patients.

This study was designed to investigate the prevalence of metallo-ß-lactamases (MBL) and extended-spectrum ß -lactamases (ESBL) in P. aeruginosa isolates collected from two different hospitals in Cairo, Egypt. Antibiotic susceptibility testing and phenotypic screening for ESBLs and MBLs were performed on 122 P. aeruginosa isolates collected in the period from January 2011 to March 2012. MICs were determined. ESBLs and MBLs genes were sought by PCR. The resistant rate to imipenem was 39.34%. The resistance rates for P. aeruginosa to cefuroxime, cefoperazone, ceftazidime, aztreonam, and piperacillin/tazobactam were 87.7%, 80.3%, 60.6%, 45.1%, and 25.4%, respectively. Out of 122 P. aeruginosa, 27% and 7.4% were MBL and ESBL, respectively. The prevalence of bla(VIM-2), bla(OXA-10(-)), bla(VEB-1), bla(NDM(-)), and bla(IMP-1)-like genes were found in 58.3%, 41.7%, 10.4%, 4.2%, and 2.1%, respectively. GIM-, SPM-, SIM-, and OXA-2-like genes were not detected in this study. OXA-10-like gene was concomitant with VIM-2 and/or VEB. Twelve isolates harbored both OXA-10 and VIM-2; two isolates carried both OXA-10 and VEB. Only one strain contained OXA-10, VIM-2, and VEB. In conclusion, bla(VIM-2)- and bla(OXA-10)-like genes were the most prevalent genes in P. aeruginosa in Egypt. To our knowledge, this is the first report of bla(VIM-2), bla(IMP-1), bla(NDM), and bla(OXA-10) in P. aeruginosa in Egypt.

Comparing a combination of penicillin G and gentamicin to a combination of clindamycin and amikacin as prophylactic antibiotic regimens in prevention of clean contaminated wound infections in cancer surgery.

BACKGROUND AND AIM: Appropriate antibiotic selection and timing of administration for prophylaxis are crucial to reduce the likelihood of surgical site infection (SSI) after a clean contaminated cancer surgery. Our aim is to compare the use of two prophylactic antibiotic (PA) regimens as regards efficacy, timing, and cost. PATIENTS AND METHODS: Two hundred patients with gastric, bladder, or colorectal cancer were randomized to receive preoperative PA, group A received penicillin G sodium and gentamicin and group B received clindamycin and amikacin intravenously. The demographic data of patients were collected, and they were observed for wound infections. RESULTS: Infected wounds occurred in 19 patients with a rate of 9.5%. Highest incidence of SSI was among bladder cancer patients (14.2%); p=0.044. The rate of SSI was 11% in group A, and 8% in group B, p=0.469. The cost of PA administered in group A was significantly less than that of group B (21.96±3.22LE versus 117.05±12.74LE, respectively; p<0.001). SSI tended to be higher among those who had longer time for antibiotic and incision (≥30min) than those who had shorter time interval (<30min), (13% vs. 6.5%, respectively). CONCLUSION: Both penicillin+gentamicin and clindamycin+amikacin are safe and effective for the prevention of SSI in clean contaminated operative procedures. In a resource limited hospital, a regimen including penicillin+gentamicin is a cost-effective alternative for the more expensive and broader coverage of clindamycin+amikacin. Timing of PA is effective in preventing SSIs when administered 30min before the start of surgery.

Antibiotic resistance is associated with longer bacteremic episodes and worse outcome in febrile neutropenic children with cancer.

PURPOSE: With the increasing emergence of multiresistant pathogens, better understanding of these infections is necessary. The aim of the present study was to evaluate the risk factors associated with isolating a multiresistant organism (MRO) from a positive blood culture in pediatric cancer patients with febrile neutropenia (F&N), and to study its impact on clinical course and outcome of febrile episodes. PATIENTS AND METHODS: The association between MRO with underlying malignancy, age, disease status, hospitalization during episode, absolute neutrophil count, absolute monocyte count, clinical foci of infection, and pathogens isolated was assessed in bacteremic pediatric cancer patients. The MRO phenotype was defined as diminished susceptibility to ≥3 of the broad spectrum antibody classes. RESULTS: Among 239 episodes of blood stream infections (BSI), Gram-positive, and Gram-negative organisms were detected in 180 (75%), and 59(25%) episodes, respectively; with 38% of isolates showing multiresistance (n = 92). Significant risk factors (P < 0.05) for MRO were hospitalization, Gram-negative organisms, presence of clinical focus of infection, reduced ANC, prolonged duration of neutropenia, and previous intake of antibiotics. Of the episodes with prolonged duration of fever extending for more than 7 days 62% (64|93) were associated with a multiresistant phenotype, while it accompanied 72% (18|25) of the cases with an unfavorable outcome; P-value <0.001. CONCLUSION: Isolation of MRO is more likely to be associated with a prolonged course and an unfavorable outcome. Continuous multidisciplinary surveillance of BSI is warranted to develop strategies for antimicrobial resistance control.

Clinical implications of icaA and icaD genes in coagulase negative staphylococci and Staphylococcus aureus bacteremia in febrile neutropenic pediatric cancer patients.

BACKGROUND: Staphylococci are the most frequently isolated organisms from blood cultures of febrile neutropenic (FN) cancer patients. We aimed to define the nature of these isolates by studying the prevalence of icaA and icaD genes in coagulase-negative staphylococci (CoNS) and Staphylococcus aureus isolates in relation to clinical and microbiological features. PROCEDURE: Fifty-five CoNS and S. aureus isolates from blood cultures of FN pediatric patients receiving chemotherapy were tested for slime production using Congo red agar plate test (CRA test), and for the presence of icaA and icaD genes by PCR. RESULTS: Of the CoNS isolates, eight were positive for ica genes, and three were slime positive/ica negative. A total of 11 (24.4%) cases of CoNS bacteremia were either ica genes or CRA test positive. There was a concordance between ica genes and CRA test positivity (P < 0.001). S. aureus isolates exhibited icaA and icaD genes more than CoNS isolates (P = 0.03). Vancomycin was significantly more prescribed in episodes of ica-positive cases (P = 0.029). CONCLUSIONS: The results of the present study support the hypothesis that the ica genes are important virulence markers for clinically significant CoNS isolates, indicating their ability to produce slime. This could be used to assign a group with higher risk FN. On the other hand, absence of these genes may permit, along with other clinical criteria, the consideration of a low-risk FN episode and allow for safe early discharge.

Profile of infections in newly diagnosed patients with acute leukemia during the induction phase of treatment.

BACKGROUND AND PURPOSE: Acute leukemia is the most common pediatric malignancy. Despite the significant progress in the treatment of infectious complications, infection-related morbidity and mortality continue to be of great importance. Prompt initiation of the appropriate empiric antibiotic treatment has improved infection outcome. The aim of the present study is to assess the type, frequency, and severity of infectious complications in a cohort of pediatric cancer patients treated at a single medical institution. We also aim to identify factors affecting bloodstream infections in newly diagnosed ALL and AML pediatric patients during the induction phase of treatment. PATIENTS AND METHODS: This study was carried out at the Department of Pediatric Oncology, National Cancer Institute, Cairo University, during the time period from January 1st to June 30th 2007. Inclusion criteria were pediatric age group (from 0-16 years), newly diagnosed acute leukemia, positive blood culture and documented site of infection. Data were analyzed using the SPSS package version 15. A p-value ≤0.05 was considered significant. RESULTS: This is a retrospective study including 100 newly diagnosed cases of acute leukemia. Fifty-four patients had ALL, and 46 patients had AML. 348 infectious episodes were recorded. Blood stream infections (BSI) occurred once or twice in 32%, 3-4 episodes in 58%, and five or more episodes in 10% of the cases. Gram-positive cocci were the most frequently observed cause of BSI, accounting for 77.9% of the total isolates followed by Gram negative organisms seen in 18.9% and mixed infections in 8%. The majority of the episodes (n= 208, 58.4%) responded to first-line empirical antibiotic therapy. CONCLUSION: Clinical and laboratory risk factors could be identified and can help prediction of serious BSI. KEY WORDS: Acute leukemia - Blood stream infection - Bacterial infection - Pediatric cancer patients.

Early hospital discharge versus continued hospitalization in febrile pediatric cancer patients with prolonged neutropenia: A randomized, prospective study.

BACKGROUND: Hospitalization with single or multi-agent antibiotic therapy has been the standard of care for treatment of febrile neutropenia in cancer patients. We hypothesized that an empiric antibiotic regimen that is effective and that can be administered once-daily will allow for improved hospital utilization by early transition to outpatient care. PROCEDURE: Febrile pediatric cancer patients with anticipated prolonged neutropenia were randomized between a regimen of once-daily ceftriaxone plus amikacin (C + A) and imipenem monotherapy (control). Afebrile patients on C + A satisfying "Early Discharge Criteria" at 72 hr continued treatment as outpatients. We compared the outcome, adverse events, duration of hospitalization, and cost between both groups. RESULTS: A prospective randomized controlled clinical trial was conducted on 129 febrile episodes in pediatric cancer patients with prolonged neutropenia. No adverse events were seen in 32 children (84% of study arm) treated on an outpatient basis. We found a statistically significant difference between the duration of hospitalization of the C + A group [median 5 days] and control [median 9 days](P < 0.001), per episode antibiotic cost (P < 0.001) and total episode cost (P < 0.001). There was no statistically significant difference in the response to treatment at 72 hr or after necessary antimicrobial modifications. CONCLUSIONS: We conclude that pediatric febrile cancer patients initially considered at risk for sepsis due to prolonged neutropenia can be re-evaluated at 72 hr for outpatient therapy. The convenience, low incidence of adverse effects, and cost benefit of the once-daily regimen of C + A may be particularly useful to reduce the overall treatment costs and duration of hospitalization.