Cephalosporin Agents Research Articles

In Vitro Evolution of Cefiderocol Resistance in an NDM-Producing Klebsiella pneumoniae Due to Functional Loss of CirA.

ABSTRACTBy serially exposing an NDM-producing Klebsiella pneumoniae clinical strain to cefiderocol, we obtained a mutant with cefiderocol MIC of >128 μg/ml. The mutant contained an early stop codon in the iron transporter gene cirA, and its complementation fully restored susceptibility. The cirA-deficient mutant was competed out by the parental strain in vitro, suggesting reduced fitness.IMPORTANCE Cefiderocol, a newly approved cephalosporin agent with an extensive spectrum of activity against Gram-negative bacteria, is a siderophore cephalosporin that utilizes iron transporters to access the bacterial periplasm. Loss of functional CirA, an iron transporter, has been associated with cefiderocol resistance. Here, we show that such genetic change can be selected under selective pressure and cause high-level cefiderocol resistance, but with a high fitness cost. Whether these resistant mutants can survive beyond selective pressure will inform stewardship of this agent in the clinic.

Implementation of a Pharmacist-Driven Penicillin and Cephalosporin Allergy Assessment Tool: A Pilot Evaluation.

Penicillin is the most commonly reported drug allergy despite the low incidence of true immune-mediated reactions. Penicillin allergy labels have been shown to lead to significant patient, institutional, and public health care consequences. This project's purpose was to improve quality of care for patients with penicillin and cephalosporin allergies, admitted to a pediatric institution, by implementation of a pharmacist-driven allergy assessment tool. A group of physicians, pharmacists, and a nurse collaborated for process development. The process was standardized, and a tool was created to assist with assessments. Pharmacists were educated on the importance of this quality improvement project and trained on the process and tool used. Implementation occurred on March 2, 2020. During the 3-month implementation period, 40 patients were admitted with a documented penicillin or cephalosporin allergy. Of these, 11 patients (27.5%) received an allergy assessment. Most were identified as having low or moderate risk of recurrent reaction with future use of a penicillin or cephalosporin agent (81.8%), and 2 patients (18.2%) were de-labeled from their documented allergy. Penicillin and cephalosporin allergy assessment implementation at a pediatric hospital was successfully implemented and allowed for identification and initiation of future quality improvement projects including implementation of penicillin skin testing and direct oral amoxicillin challenges.

Arthritis-Dermatitis Syndrome: a Case of Disseminated Gonococcal Infection with Petechial Skin Rash

A previously healthy 36-year-old woman was admitted to the hospital with vaginal discharge, bilateral ankle pain, and a lower extremity skin rash, all of which developed after unprotected vaginal intercourse with a new male partner. On examination, there was a petechial and purpuric rash involving the lower extremities and bilateral tenosynovitis of the ankle dorsiflexor tendons. Urine NAAT was positive for Neisseria gonorrhea, confirming disseminated gonococcal infection (DGI). The patient was initially treated with oral azithromycin and intravenous ceftriaxone, but as a result of psychosocial circumstances, she was prematurely discharged on an oral cephalosporin agent. She represented with treatment-failure DGI and was treated with a 7-day course of intramuscular ceftriaxone. Repeat urine NAAT was negative for gonorrhea and the patient remained asymptomatic. This case features an atypical cutaneous manifestation of DGI, characterized by a painless petechial and purpuric skin rash rather than the tender papulo-pustular lesions that are typically seen. Additionally, it highlights the importance of DGI treatment with a 7-day parenteral cephalosporin therapy when antibiotic susceptibility is not available.

Prevalence of OXA-type Class D β-lactamases Among Clinical Isolates of Klebsiella Pneumoniae in Multiple Centers of Tehran, Iran.

Drug- and multidrug-resistant Klebsiella pneumoniae isolates have been found worldwide. Treatment failures against carbapenems and extended-spectrum cephalosporins, the currently recommended drugs, contribute to consider K. pneumoniae infections as untreatable infections. The emergence and spread of oxacillinases (OXAs) with carbapenem-hydrolyzing properties are a major concern and seriously become a public health problem worldwide. The present study was aimed to explore the blaOXA genes among clinical isolates of K. pneumoniae in some clinical settings in Tehran, Iran. A total of 90 K. pneumoniae isolates were collected from different clinical samples at hospitals in Tehran during the year 2016 and 2018. Antimicrobial susceptibility testing was performed on bacterial isolates using the Kirby-Bauer disc diffusion method on Mueller Hinton agar plates. PCR experiments were carried out to detect the presence of the blaOXA genes, including blaOXA- 1, blaOXA-2, blaOXA-4, blaOXA10, and blaOXA-48-like, using specific primers. The antibiotics susceptibility results showed that 41% of the K. pneumoniae isolates were resistant to imipenem and meropenem. Resistance rates for cephalosporin agents, including cefpodoxime, ceftazidime, cefuroxime, cefotaxime, and cefepime, were measured as 72.3%, 67.8%, 67.7%, 65.5%, and 60%, respectively. In the present study, 51.1% of isolates were classified as multidrug-resistant K. pneumoniae strains. The molecular assays showed that 56.6% of isolates harbored blaOXA-2. In addition, blaOXA-4, blaOXA-1, blaOXA-10, and blaOXA-48-like genes were also found in 16.7%, 5.6%, 1.1%, and 1.1% of isolates, respectively. The spread of blaOXAs, especially blaOXA-48-like, among K. pneumoniae isolates indicated the inadequate dissemination control of multidrug-resistant bacteria in the Iranian hospital environment. There is a reason to assume that OXA producing K. pneumoniae will limit clinical therapeutic options in the future and pose threats to national public health among the Iranian population.

PD32-01 NATIONAL PRESCRIBING TRENDS AMONG ADULTS WITH URINARY TRACT INFECTIONS: FINDINGS FROM THE UROLOGIC DISEASES IN AMERICA PROJECT

You have accessJournal of UrologyGeneral & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making III (PD32)1 Apr 2020PD32-01 NATIONAL PRESCRIBING TRENDS AMONG ADULTS WITH URINARY TRACT INFECTIONS: FINDINGS FROM THE UROLOGIC DISEASES IN AMERICA PROJECT Lydia Feinstein*, Brian R. Matlaga, Kevin C. Abbott, Tamara Bavendam, Ziya Kirkali, Erline Martinez-Miller, and Julia B. Ward Lydia Feinstein*Lydia Feinstein* More articles by this author , Brian R. MatlagaBrian R. Matlaga More articles by this author , Kevin C. AbbottKevin C. Abbott More articles by this author , Tamara BavendamTamara Bavendam More articles by this author , Ziya KirkaliZiya Kirkali More articles by this author , Erline Martinez-MillerErline Martinez-Miller More articles by this author , and Julia B. WardJulia B. Ward More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000896.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Concerns of multidrug resistance may be influencing prescribing practices for urinary tract infections (UTI). We assessed 10-year trends in pharmacotherapy for UTI among a large sample of US adults treated in outpatient settings. METHODS: We assessed trends in the prevalence of UTI-related prescription fills and medication duration from 2007-2016. To assess trends among those aged 18-64 years (N= 2,691,529 UTI episodes), we utilized the Optum© Clinformatics® Data Mart (CDM), a de-identified administrative claims database that includes individuals covered by commercial insurance in all 50 US states. For analyses among those aged ≥65 years (N=874,043 UTI episodes), we utilized the Medicare 5% Sample. UTI was defined as an outpatient claim with a UTI-related diagnosis code followed by a pharmacy claim for an anti-infectious agent within 72 hours. RESULTS: The most commonly used medications were quinolones, urinary anti-infectives, and sulfonamides (Table 1). Quinolone use was more common among men compared to women, while urinary anti-infective use was more common among women. The mean duration of medication use was 8 days, with variation by medication type (range: 5-16 days). Over time, quinolone use decreased while the use of urinary anti-infectives, cephalosporins, and combination therapy including azoles increased (Figure 1). CONCLUSIONS: Pharmacological treatment of UTI evolved over the 10-year study period, shifting from a primarily quinolone-based treatment paradigm to a more diverse pharmaceutical armamentarium that increasingly relied on cephalosporin agents. This evolution was likely driven by resistance patterns that particularly impact the effectiveness of quinolone agents. Nevertheless, regardless of the antibacterial agent used, treatment duration appeared to be longer than what guidelines typically suggest, representing an opportunity for practice improvement. Source of Funding: Funded by the NIH via a contract to Social & Scientific Systems. © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e636-e636 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Lydia Feinstein* More articles by this author Brian R. Matlaga More articles by this author Kevin C. Abbott More articles by this author Tamara Bavendam More articles by this author Ziya Kirkali More articles by this author Erline Martinez-Miller More articles by this author Julia B. Ward More articles by this author Expand All Advertisement PDF downloadLoading ...

Antimicrobial Prophylaxis for the Prevention of Surgical Site Infections in Orthopaedic Oncology - A Narrative Review of Current Concepts.

The incidence of surgical site infections (SSIs) after elective tumour orthopaedic surgery in adults is higher than non-oncologic orthopaedic surgery. Their causative microorganisms and antibiotic susceptibilities are also different from the non-oncologic cases; with no apparent predictable microbiological patterns. Clinicians continue to struggle to tailor the optimal prophylactic regimen for the very heterogeneous group of tumour patients. Many clinicians thus prolong the first-and second-generation cephalosporin agents, while a minority chooses to broaden the antimicrobial spectrum by combination prophylaxis. The variability in current practices and surgical techniques is enormous, even within the same setting. The scientific literature lacks adequate retrospective case-studies and there is currently only one prospective randomized trial. In this narrative review, we discuss various perioperative antibiotic concepts in oncologic orthopaedic surgery, including a summary of the state-to-the-art, opinions and difficulties related to the different prophylactic strategies.

1164. County-Level Geographic Distribution of Extended-Spectrum Cephalosporin-Resistant Enterobacteriaceae Across Outpatient Settings of the Veterans Health Administration, 2000–2017

BackgroundExtended-spectrum cephalosporin resistance (ESCR) among Enterobacteriaceae has emerged globally over the last two decades, with increased prevalence in the community. Data from European countries and healthcare-associated isolates in the United States have demonstrated substantial geographic variability in the prevalence of ESCR, but community-onset isolates in the United States have been less studied. We aimed to describe geographic distribution and spread of ESCR among outpatient settings across the Veterans Health Administration (VHA) over 18 years.MethodsWe analyzed a retrospective cohort of all patients who had any positive clinical culture specimen for ESCR Enterobacteriaceae collected in an outpatient setting; ESCR was defined by phenotypic nonsusceptibility to at least one extended-spectrum cephalosporin agent or detection of an extended-spectrum β-lactamase. Patient-level data were grouped by county of residence, and the total number of unique patients who received care within VHA for each county was used as a denominator. We aggregated data by time terciles (2000–2005, 2006–2011, and 2012–2017), and overall and county-level incidence rates were calculated as the number of unique patients in each year with ESCR Enterobacteriaceae per person-year.ResultsDuring the study period, there were 1,980,095 positive cultures for Enterobacteriaceae from 870,797 unique patients across outpatient settings of VHA, from a total of 107,404,504 person-years. Among those, 136,185 cultures (6.9%) from 75,500 unique patients (8.7%) were ESCR. The overall incidence rate was 9.0 cases per 10,000 person-years, which increased from 6.3 per 10,000 person-years in 2000 to 14.6 per 10,000 person-years in 2017. County-level incidence rates ranged widely but increased overall (interquartile range [IQR] in 2000–2005: 0–6.7; 2006–2011: 0–9.1; 2012–2017: 3.1–14.3 per 10,000 person-years), with some geographic clustering (figure).ConclusionThis study demonstrates that there has been geographic variation both in incidence rates and trends of ESCR Enterobacteriaceae in outpatient settings of VHA, which suggests the importance of tailoring local antibiotic-prescribing guidelines incorporating geographic variability in epidemiology. Disclosures M. Ohl, Gilead Sciences, Inc.: Grant Investigator, Research grant.

Increasing clinical resistance rate of Shigella sonnei to cefotaxime in Jiangsu Province, China, between 2012 and 2015.

The objective of this study is to evaluate the prevalence of Shigella sonnei (S. sonnei) and characterize the mechanism of its increasing resistance to cefotaxime, a third-generation cephalosporin agent between 2012 and 2015. We investigated the drug resistance in 95 isolates of S. sonnei by K-B dilution method and isolates with the extended-spectrum beta-lactamases (ESBLs)-producing genes were detected by polymerase chain reaction (PCR) and sequencing. Over a 4-year period, the resistance rate of S. sonnei to cefotaxime increased from 31.6% to 64.3%, between 2012 and 2015. Molecular characterization of the ESBL genes, comprising 28 strains of CTX-M-1 group: blaCTX-M-55 (n=22), blaCTX-M-3 (n=3) and blaCTX-M-15 (n=3); 11 strains of CTX-M-9 group: blaCTX-M-14 (n=9) and blaCTX-M-65 (n=2), and 36 strains with blaTEM-1 gene. None of S. sonnei isolates carried blaCTX-M-2 group and SHV-type. The antimicrobial resistance rate of S. sonnei to cefotaxime significantly increased. Accordingly, regular surveillance of the cephalosporin-resistant S. sonnei should be emphasized. Moreover, exploration of the mechanism underlying the resistance of S. sonnei to cefotaxime contributes to the prophylaxis of further emergence of drug resistance.

Pharmacokinetic drug evaluation of ceftobiprole for the treatment of MRSA

ABSTRACTIntroduction: Methicillin-resistant Staphylococcus aureus (MRSA), while decreasing in overall incidence, is still a prominent concern world-wide. New agents coming to market in the last 10 years allow practitioners to optimize treatment for MRSA infections. Ceftobiprole is a cephalosporin agent with MRSA activity, currently approved in selected countries for the treatment of community-acquired pneumonia and hospital-acquired pneumonia.Areas covered: Relevant literature regarding spectrum of activity, pharmacokinetics, pharmacodynamics, and clinical trials will be discussed.Expert opinion: Ceftobiprole is an addition to a growing number of antimicrobials with activity against MRSA. Concern for appropriate dosing in critically ill patients remains due to its ineffectiveness for the treatment of ventilator-associated pneumonia (VAP). While ceftobiprole has activity against gram-negative organisms, the allowance for use of an additional agent for gram-negative infections in clinical trials limits recommendations for monotherapy for empirical treatment of HAP. Ceftobiprole’s place in therapy will lie in its activity against gram positive organisms, such as Streptococcus spp. and Staphylococcus spp.

Gram-Negative Bacilli in Infants Hospitalized in The Neonatal Intensive Care Unit.

Gram-negative bacilli (GNB) account for a significant burden of infection and colonization in neonatal intensive care units (NICUs), and antibiotic resistance among these pathogens is of increasing concern. A prospective cohort study was performed in 4 NICUs between May 2009 and April 2012. The body sites from which GNB were isolated, antimicrobial susceptibilities of the GNB isolated, and antimicrobial therapy were assessed. Attending neonatologists treated 3.0% (188 of 6184) of eligible infants for GNB infection; 23% of 214 GNB isolates were nonsusceptible to antimicrobial agents, including gentamicin (14.8%), piperacillin-tazobactam (9.9%), third-generation cephalosporin (7.0%), and/or carbapenem agents (4.5%). Gentamicin was the most commonly used antibiotic overall, and much of its use was empiric. However, third-generation cephalosporin agents and cefepime were used more commonly as targeted therapy for identified Gram-negative pathogens. One-quarter of the GNB isolates were nonsusceptible to ≥1 antibiotic. Antimicrobial stewardship strategies for reducing antimicrobial use in NICUs should be implemented.

Colonization With Antimicrobial-Resistant Gram-Negative Bacilli at Neonatal Intensive Care Unit Discharge.

The epidemiology of the colonization of infants with antimicrobial-resistant Gram-negative bacilli (GNB) at discharge from the neonatal intensive care unit (NICU) is not well understood. A multicenter study in which rectal surveillance samples for culture were obtained at NICU discharge from infants hospitalized ≥14 days was performed. Factors associated with colonization with GNB resistant to gentamicin, third/fourth-generation cephalosporin agents, or carbapenem agents were assessed by using a fixed-effects model. Of these infants, 9% (119 of 1320) were colonized with ≥1 antimicrobial-resistant GNB. Prolonged treatment (≥10 days) with meropenem or third/fourth-generation cephalosporin agents or treatment for ≥5 days with a β-lactam/β-lactamase combination agent were associated with an increased risk of colonization with GNB resistant to gentamicin. Surgery and ≥5 days of treatment with third/fourth-generation cephalosporin agents, a β-lactam/β-lactamase combination agent, or metronidazole were associated with an increased risk of colonization with GNB resistant to third/fourth-generation cephalosporin agents. Female sex and prolonged treatment (≥10 days) with meropenem were associated with colonization with GNB resistant to carbapenem agents. Prolonged treatment with broad-spectrum antibiotics was associated with the colonization of infants with antimicrobial-resistant GNB within 7 days of NICU discharge. These findings suggest the potential for dissemination of resistant GNB from colonized infants to other NICUs, the community, or pediatric long-term care facilities. Antimicrobial stewardship efforts aimed at improving appropriate antibiotic use could have a beneficial effect on the emergence of antimicrobial-resistant GNB in the NICU population.

Direct reporting cefazolin from VITEK® 2 forE. coli,K. pneumoniaeandP. mirabilisisolated from urine cultures using new CLSI interpretations

Background: In recent years, Clinical and Laboratory Standard Institute (CLSI) has recommended a series breakpoint changes for cefazolin, including testing it as a surrogate agent for oral cephalosporins for treating uncomplicated urinary tract infections (uUTIs). Objectives: This study was conducted to evaluate the feasibility of direct reporting the cefazolin results from VITEKO 2 for E. coli, K. pneumoniae, K. oxytoca and P. mirabilis isolated from patients with uUTIs using 2014 CLSI recommendation. Material and Methods: Cefazolin susceptibility results of urine cultures of the above four species generated from January 1, 2013 December 31, 2013, using both GN AST card N208 on VITEKO 2 and cefazolin disk (gold standard) methods, were extracted from SoftMic Laboratory Information System and analyzed for their category agreement using 2014 CLSI interpretations. Results: Cefazolin susceptibilities of 1969 urinary isolates (1869 patients) of E. coli, K. pneumoniae/K. oxytoca and P. mirabilis comparing their VITEKO 2 and disk test results, category agreement for cefazolin tested with both methods was 98%. The linear correlation between sensitive cefazolin and sensitive cephalothin MICs versus cefazolin zone diameters was good, with a predictive value of 99%. Conclusion: It is acceptable to report cefazolin directly from VITEKO 2 for the named species from urine cultures. The susceptibility correlation among cefazolin, cephalothin and cefixime were excellent (excluded non-susceptible), further testing with individual oral cephalosporin agents, in this institute, may not be necessary. Recommendation: Final report accompanied by a comment in accordance with 2014 CLSI guideline is recommended to provide therapeutic guidance to clinicians. Key Word: Cefazolin, Urine Culture, CLSI, Interpretations, VITEKO 2

In vitro activities of first-generation cephalosporin agents against oral streptococci from odontogenic infections between 2005 to 2015 years

In vitro activities of first-generation cephalosporin agents against oral streptococci from odontogenic infections between 2005 to 2015 years

Antimicrobial activity of ceftaroline and other anti-infective agents against microbial pathogens recovered from the surgical intensive care patient population: a prevalence analysis.

Ceftaroline is a new parenteral cephalosporin agent with excellent activity against methicillin-sensitive (MSSA) and resistant strains of Staphylococcus aureus (MRSA). Critically ill surgical patients are susceptible to infection, often by multi-drug-resistant pathogens. The activity of ceftaroline against such pathogens has not been described. Three hundred thirty-five consecutive microbial isolates were collected from surgical wounds or abscesses, respiratory, urine, and blood cultures from patients in the surgical intensive care unit (SICU) of a major tertiary medical center. Using Clinical and Laboratory Standards Institute (CLSI) standard methodology and published breakpoints, all aerobic, facultative anaerobic isolates were tested against ceftaroline and selected comparative antimicrobial agents. All staphylococcal isolates were susceptible to ceftaroline at a breakpoint of ≤1.0 mcg/mL. In addition, ceftaroline exhibited excellent activity against all streptococcal clinical isolates and non-ESBL-producing strains of Enterobacteriaceae (93.5%) recovered from SICU patients. Ceftaroline was inactive against ESBL-producing Enterobacteriaceae, Pseudomonas aeruginosa, vancomycin-resistant enterococci, and selective gram-negative anaerobic bacteria. At present, ceftaroline is the only cephalosporin agent that is active against community and healthcare-associated MRSA. Further studies are needed to validate the benefit of this novel broad-spectrum anti-infective agent for the treatment of susceptible serious infections in the SICU patient population.

Answer to March 2014 Photo Quiz

Answer: Bacteremia caused by Tsukamurella tyrosinosolvens. The isolate was definitively identified as Tsukamurella tyrosinosolvens via DNA sequence analysis of the 16S rRNA gene. Similar to those of aerobic actinomycetes such as Gordonia spp., Rhodococcus spp., and Nocardia spp., cell walls of Tsukamurella spp. contain mycolic acids and allow for a weakly positive reaction upon modified acid-fast staining (1). The longer bacillary form of Tsukamurella spp. potentiates preliminary differentiation from Gordonia spp. (short coryneform bacilli) and Rhodococcus spp. (some coccoid forms) (1). Additional phenotypic delineation of Tsukamurella spp. can be guided with demonstration of growth in lysozyme (also Nocardia spp.) and specialized characterization of mycolic acid and menaquinone chemistry. However, molecular techniques, particularly those centered on gene sequencing, are necessary for definitive identification of aerobic actinomycetes to both the genus and species levels (1). Tsukamurella spp. have been documented to be etiologies of clinical disease, with reports increasing in recent years. Within a 12-year period at a university hospital, Liu et al. (2) rank ordered isolates of T. tyrosinosolvens, Tsukamurella spumae, and Tsukamurella pulmonis in the context of keratitis or catheter-related bloodstream infection. On rare occasions, Tsukamurella paurometabola has also been implicated in clinical disease (1). Specific to T. tyrosinosolvens, a recent report by Karunakaran et al. (3) typified a common clinical presentation. A catheter-related bloodstream infection in a 51-year-old hematology patient was resolved via catheter removal and an imipenem regimen. T. tyrosinosolvens has also been implicated in cerebellar abscess (4) and presentations of respiratory disease (5, 6). The two preceding citations shared an underlying status of immunosuppression, ranging from antecedent lung transplantation to delivery of chemotherapeutic agents by a central venous catheter. The cerebellar abscess presented in an immunocompetent patient with predisposing chronic otitis media that was refractory to penicillin and cephalosporin agents. Antimicrobial susceptibility testing was not performed on this isolate, due to the inconclusive utility of the Clinical and Laboratory Standards Institute standards for testing aerobic actinomycetes other than Nocardia spp. (7). Liu et al. (2), in a limited data set, suggested that T. pulmonis yielded higher MICs for clindamycin, erythromycin, vancomycin, and tetracycline than other Tsukamurella spp. Antimicrobials with lower MICs across multiple species included gentamicin, levofloxacin, and ciprofloxacin. Similar to data reported by Karunakaran et al. (3), our patient defervesced quickly upon removal of the peripherally inserted central catheter (PICC) line and initiation of antimicrobial therapy. The patient was discharged to home on parenteral vancomycin therapy. (See page 711 in this issue [doi:10.1128/JCM.03462-12] for photo quiz case presentation.)

Approach to Antimicrobial Prophylaxis for Urology Procedures in the Era of Increasing Fluoroquinolone Resistance

To evaluate rationale antimicrobial prophylaxis options in patients undergoing urologic procedures in the era of increasing fluoroquinolone resistance. Literature was accessed through MEDLINE (1980-October 2013) using the search terms "urologic surgical procedures," "antibiotic prophylaxis," and "drug resistance." Pertinent article titles and abstracts were reviewed by the authors in addition to reference citations from publications. All English language publications identified were evaluated. The American Urology Association guidelines recommend fluoroquinolones (FQs) as first-line agents for preoperative prophylaxis to prevent infection after urologic procedures. Since the latest publication of these guidelines in 2008, resistance within this class of drugs has been increasing especially among common urologic pathogens like Escherichia coli. Limited data are available to support non-FQ alternatives for preoperative prophylaxis, and small studies published prior to 2000 have been conducted using such regimens with success. FQs have become the mainstay of prophylaxis in this population because of ease of administration, relatively low cost, and excellent oral bioavailability; however, β-lactam class antimicrobials may be emerging as effective alternatives based on more favorable resistance profiles. Based on the current available literature, geographic areas with increasing FQ resistance should consider using cephalosporin agents as alternatives for prophylaxis in patients undergoing urologic procedures, reserving FQ in patients unable to tolerate β-lactams because of type-1 hypersensitivity reactions or other adverse effects.

Clinical Pharmacodynamics of Antipseudomonal Cephalosporins in Patients with Ventilator-Associated Pneumonia

Advanced-generation cephalosporins are frequently used for empirical coverage of ventilator-associated pneumonia (VAP) due to their activity against a broad spectrum of Gram-positive and Gram-negative aerobic bacteria, including Pseudomonas aeruginosa and Enterobacteriaceae. Providing optimal antibiotic exposure is essential to achieving successful response in patients with VAP. We evaluated exposures of two antipseudomonal cephalosporins, ceftazidime and cefepime, in patients with VAP due to Gram-negative bacilli to identify the pharmacodynamic parameter predictive of microbiological success. Population pharmacokinetic models were used to estimate individual free drug exposures. Pharmacodynamic indices were determined for each patient using the baseline Gram-negative bacilli with the highest drug MIC. Classification and regression tree analysis was utilized to partition exposure breakpoints, and multivariate logistic regression was conducted to identify predictors of microbiological success. A total of 73 patients (18 receiving ceftazidime therapy and 55 receiving cefepime therapy) were included. MICs ranged widely from 0.047 to 96 μg/ml. The microbiological success rate was 58.9%. Predictive breakpoints were identified for all pharmacodynamic parameters, including a serum fT>MIC greater than 53% (P=0.02). When controlling for APACHE II (odds ratio [OR], 1.01; 95% confidence interval, 0.93 to 1.09; P=0.85) and combination therapy (OR, 0.74; 95% confidence interval, 0.25 to 2.19; P=0.59), achieving a greater than 53% fT>MIC remained a significant predictor of success (OR, 10.3; 95% confidence interval, 1.1 to 92.3; P=0.04). In patients with VAP due to Gram-negative bacilli, serum exposure of greater than 53% fT>MIC was found to be a significant predictor of favorable microbiological response for antipseudomonal cephalosporins. These data are useful when determining dosing regimens for cephalosporin agents under development for pneumonia.

Spectrum and potency of ceftaroline against leading pathogens causing community-acquired respiratory tract and skin and soft tissue infections in Latin America, 2010

Ceftaroline, the active metabolite of the prodrug ceftaroline fosamil, is a cephalosporin with in vitro bactericidal activity against Gram-positive organisms, including methicillin-susceptible and -resistant Staphylococcus aureus, β-haemolytic and viridans group streptococci, and Streptococcus pneumoniae, as well as common Gram-negative organisms. In this study a total of 986 isolates collected in 2010 from patients in 15 medical centers in five Latin American countries from the Assessing Worldwide Antimicrobial Resistance Evaluation Program were identified as community-acquired respiratory tract or skin and soft tissue infection pathogens. Ceftaroline was the most potent agent tested against S. pneumoniae with a MIC90 value (0.12μg/mL) that was eight-fold lower than ceftriaxone, levofloxacin, and linezolid. Its spectrum of coverage (100.0% susceptible) was similar to tigecycline, linezolid, levofloxacin and vancomycin. Against Haemophilus influenzae and Moraxella catarrhalis, ceftaroline was the most active agent tested. The activity of ceftaroline against S. aureus (including MRSA) was similar to that of vancomycin and tetracycline (MIC90, 1μg/mL) and linezolid (MIC90, 2μg/mL). The β-haemolytic streptococci exhibited 100.0% susceptibility to ceftaroline. Ceftaroline activity against Escherichia coli, Klebsiella spp., and Enterobacter spp. was similar to that of ceftriaxone and ceftazidime. These parenteral cephalosporin agents have potent activity against non-extended-spectrum β-lactamase-phenotype strains, but are not active against extended-spectrum β-lactamase-phenotype strains. These results confirm the in vitro activity of ceftaroline against pathogens common in community-acquired respiratory tract and skin and soft tissue infection in Latin America, and suggest that ceftaroline fosamil could be an important therapeutic option for these infections.

Ventriculoperitoneal Shunt Infections in Adult Patients

Ventriculoperitoneal Shunt Infections in Adult Patients

Ventriculoperitoneal Shunt Infections in Adult Patients

Ventriculoperitoneal Shunt Infections in Adult Patients