Use Of Broad-spectrum Cephalosporins Research Articles

A Retrospective Study of Risk Factors, Mortality, and Treatment Outcomes for Infections with Carbapenemase-Producing Enterobacterales in a Tertiary Hospital in Havana, Cuba.

(1) Background: The spread of carbapenem-resistant Enterobacterales in hospitals constitutes an important epidemiological and therapeutic problem that especially affects vulnerable patients such as perioperative patients. (2) Methods: We conducted a descriptive, observational, retrospective case-control study of patients infected with carbapenemase-producing carbapenem-resistant Enterobacterales (CP-CRE) and carbapenem-susceptible Enterobacterales during the perioperative period in a tertiary hospital. (3) Results: Metallo-β-lactamase was detected in all 124 CRE isolates, with NDM-type carbapenemase being dominant, while 3 isolates coproduced KPC-type enzyme and showed high resistance rates against all antibiotics except colistin (25.2%). By analyzing the risk factors for infection, steroid use (OR: 3.22, p < 0.01), prior use of two or more antibiotics (OR: 4.04, p = 0.01), prior use of broad-spectrum cephalosporins (OR: 2.40, p = 0.04), and prior use of carbapenem (OR: 4.77, p = 0.03) were found to be independent risk factors for CP-CRE infection. In addition, in this study, we observed that the clinical outcomes of bloodstream infections and pneumonia associated with CP-CRE posed higher mortality risks. However, by analyzing the associations between treatment options and mortality, it was found that, in bloodstream infections caused by CP-CRE, colistin-based regimens showed a significant advantage (PR = 0.40, p = 0.03). (4) Conclusions: High mortality is associated with nosocomial infections in the perioperative period caused by carbapenemase-producing Enterobacterales, the dissemination of which in health care settings in Cuba remains a public health challenge.

The use of first-generation cephalosporin antibiotics, cefalexin and cefradine, is not associated with induction of simulated Clostridioides difficile infection.

ObjectivesThe use of broad-spectrum cephalosporins is associated with induction of Clostridioides difficile infection (CDI). Recent knowledge on the importance of the healthy microbiota in preventing pathogen colonization/outgrowth highlights the caution needed when prescribing broad-spectrum antibiotics. The use of historical narrow-spectrum antibiotics, such as first-generation cephalosporins, is gaining increased attention once more as they have a reduced impact on the microbiota whilst treating infections. Here, the effects of two first-generation cephalosporins, compared with a third-generation cephalosporin, on the human microbiota were investigated and their propensity to induce simulated CDI.MethodsThree in vitro chemostat models, which simulate the physiochemical conditions of the human colon, were seeded with a human faecal slurry and instilled with either narrow-spectrum cephalosporins, cefalexin and cefradine, or a broad-spectrum cephalosporin, ceftriaxone, at concentrations reflective of colonic levels.ResultsInstillation of cefalexin was associated with reduced recoveries of Bifidobacterium and Enterobacteriaceae; however, Clostridium spp. recoveries remained unaffected. Cefradine exposure was associated with decreased recoveries of Bifidobacterium spp., Bacteroides spp. and Enterobacteriaceae. These changes were not associated with induction of CDI, as we observed a lack of C. difficile spore germination/proliferation, thus no toxin was detected. This is in contrast to a model exposed to ceftriaxone, where CDI was observed.ConclusionsThese model data suggest that the minimal impact of first-generation cephalosporins, namely cefalexin and cefradine, on the intestinal microbiota results in a low propensity to induce CDI.

Carbapenem-Resistant but Cephalosporin-Susceptible Pseudomonas aeruginosa in Urinary Tract Infections: Opportunity for Colistin Sparing.

This paper briefly reports the occurrence and epidemiology of carbapenem-resistant but cephalosporin-susceptible (Car-R/Ceph-S) Pseudomonas aeruginosa isolates from urinary tract infections (UTIs) in a tertiary-care hospital in the Southern Region of Hungary, and the phenotypic characterization of the possible resistance mechanisms in these isolates. Isolates and data were collected regarding P. aeruginosa UTIs corresponding to the period between 2008 and 2017. Susceptibility testing was performed using the Kirby–Bauer disk diffusion method; minimum inhibitory concentrations (MICs) of the isolates were determined using E-tests. The phenotypic detection of ampicillin C-type (AmpC) β-lactamases, efflux pump overexpression and carbapenemase production was also performed. P. aeruginosa represented n = 575 (2.72% ± 0.64%) from outpatient, and n = 1045 (5.43% ± 0.81%) from inpatient urinary samples, respectively. Based on the disk diffusion test, n = 359 (22.16%) were carbapenem-resistant; in addition to carbapenems, n = (64.34%) were also resistant to ciprofloxacin; n = (60.17%) to gentamicin/tobramycin; n = (58.51%) to levofloxacin; and n = (27.57%) to amikacin. From among the carbapenem-resistant isolates, n = 56 (15.59%) isolates were multidrug-resistant, while n = 16 (4.46%) were extensively drug-resistant. From among the Car-R/Ceph-S isolates (n = 57), overexpression of AmpC was observed in n = 7 cases (12.28%); carbapenemase production in n = 4 (7.02%); while overexpression of efflux pumps was present in n = 31 (54.39%) isolates. To spare last-resort agents, e.g., colistin, the use of broad-spectrum cephalosporins or safe, alternative agents should be considered in these infections.

Epidemiology of extended spectrum β-lactamase, AmpC and class A carbapenemases-producing organisms isolated at San Camillo Hospital of Treviso (Italy) between April 2012 and March 2014

The indiscriminate use of broad-spectrum cephalosporins of the last years has favoured the selection of extended spectrum β-lactamases (ESBLs), AmpC and class A carbapenemases (KPC)-producing &lt;em&gt;Enterobacteriaceae&lt;/em&gt; strains, representing a real health emergency. At San Camillo Hospital of Treviso, Italy, between April 2012 and March 2014, we isolated 263 suspected ESBL-producing strains from various specimens, including urine (76.4%), wound swabs (9.9%), blood cultures (4.6%), vaginal swabs (2.7%), fragments of bone (1.5%) and other materials (4.9%). The majority of the isolated bacteria were represented by &lt;em&gt;Escherichia coli&lt;/em&gt; (43.3%), followed by &lt;em&gt;Klebsiella pneumoniae&lt;/em&gt; (34.2%), &lt;em&gt;Proteus mirabilis&lt;/em&gt; (15.2%), &lt;em&gt;Enterobacter&lt;/em&gt; spp. (3.8%), &lt;em&gt;Morganella morganii&lt;/em&gt; (1.1%), &lt;em&gt;Serratia&lt;/em&gt; spp. (0.8%), &lt;em&gt;Proteus vulgaris&lt;/em&gt; (0.4%), &lt;em&gt;Citrobacter freudii&lt;/em&gt; (0.4%), &lt;em&gt;Providencia&lt;/em&gt; spp. (0.4%) and &lt;em&gt;Pseudomonas aeruginosa&lt;/em&gt; (0.4%). Using confirmatory phenotypic tests, 89.4% of the isolated resulted ESBL producer, 15.3% of which were also AmpC-producers, 1.5% were ESBL negative and AmpC positive, 4.2% were ESBL negative and AmpC negative, and 4.9%, consisting solely of K.pneumoniae, were confirmed as KPC positive. ESBL-mediated resistance to cephalosporin is not always clearly evident using susceptibility testing performed by agar diffusion-disc or dilution methods, for this reason it is strictly recommended to use specific tests able to reveal important mechanisms of resistance. The optimal use of diagnostic tools in microbiology is necessary to fight the spreading of pathogens with multiple antibiotic resistance mechanisms and in order to avoid giving useless antibiotic therapies to the patients.

Clinical risk scoring system for predicting extended-spectrum β-lactamase-producing Escherichia coli infection in hospitalized patients

Extended spectrum β-lactamase-producing Escherichia coli (ESBL-EC) has important implications for infection control and empiric antibiotic prescribing. This study aims to develop a risk scoring system for predicting ESBL-EC infection based on local epidemiology. The study retrospectively collected eligible patients with a positive culture for E.coli during 2011 to 2014. The risk scoring system was developed using variables independently associated with ESBL-EC infection through logistic regression-based prediction. Area under the receiver-operator characteristic curve (AuROC) was determined to confirm the prediction power of the model. Predictors for ESBL-EC infection were male gender [odds ratio (OR): 1.53],age ≥55 years (OR: 1.50), healthcare-associated infection (OR: 3.21), hospital-acquired infection (OR: 2.28), sepsis (OR: 1.79), prolonged hospitalization (OR: 1.88), history of ESBL infection within one year (OR: 7.88), prior use of broad-spectrum cephalosporins within three months (OR: 12.92), and prior use of other antibiotics within three months (OR: 2.14). Points scored ranged from 0 to 47, and were divided into three groups based on diagnostic performance parameters: low risk (score: 0-8; 44.57%), moderate risk (score:9-11; 21.85%) and high risk (score: ≥12; 33.58%). The model displayed moderate power of prediction (AuROC: 0.773; 95% confidence interval: 0.742-0.805) and good calibration (Hosmer-Lemeshow χ(2)=13.29; P=0.065). This tool may optimize the prescribing of empirical antibiotic therapy, minimize time to identify patients, and prevent spreading of ESBL-EC. Prior to adoption into routine clinical practice, further validation study of the tool is needed.

Escherichia coli and Klebsiella pneumoniae bacteremia in patients with neutropenic fever: factors associated with extended-spectrum β-lactamase production and its impact on outcome

Escherichia coli and Klebsiella pneumoniae are main pathogens in neutropenic fever even if the proportion of Gram-positive cocci is increasing. Extended-spectrum β-lactamases (ESBL)-producing organisms are an emerging problem in nosocomial infection. Nevertheless, until now, information about risk factors for the acquisition and clinical outcomes of bacteremia due to ESBL-producing organisms is limited in neutropenic patients. From medical records collected between January 2007 and December 2008, we identified a total of 101 consecutive patients who developed bacteremia due to E. coli (n = 87) or K. pneumoniae (n = 14). Twenty-six (26 %) cases of bacteremia were caused by ESBL-producing organisms. A hospital stay of >2 weeks during the 3 months preceding bacteremia [adjusted odds ratio (OR), 5.887; 95 % confidence interval (CI), 1.572-22.041] and the use of broad-spectrum cephalosporins in the 4 weeks prior to bacteremia (adjusted OR, 6.186; 95 % CI, 1.616-23.683) were significantly related to the acquisition of ESBL. Twenty-four (92 %) of the ESBL-producing organisms were susceptible to either piperacillin-tazobactam or amikacin. Aminoglycosides (amikacin or isepamicin) were the main appropriate antimicrobial agents used against the ESBL-producing isolates during the initial empirical treatment (16/22, 73 %). However, the 30-day mortality rates for ESBL bacteremia and non-ESBL bacteremia were not significantly different (15 vs 5 %; p = 0.199). As alternatives to carbapenem, piperacillin-tazobactam plus amikacin or isepamicin combinations may be effective empirical therapeutic options for patients with neutropenic fever who are at high risk of developing bacteremia with ESBL-producing pathogens.

Risk Factors Associated with Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae Nosocomial Bloodstream Infections in a Tertiary Care Hospital: A Clinical and Molecular Analysis

Aim: To describe the risk factors and molecular epidemiology of nosocomial bloodstream infections caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae in a tertiary care hospital. Methods: Patients with enterobacteria-positive blood cultures were included. ESBL expression in the isolates was detected using the combination disk method. Antimicrobial susceptibility testing was performed using the disk diffusion method. bla_SHV, bla_TEM, and bla_CTX-M genes were identified in the isolated strains by PCR and sequencing. Klebsiella pneumoniae isolates were genotyped by PFGE. Results: Of the 90 isolates recovered, half were found to express ESBLs. Twenty-eight (62%) of these isolates were K. pneumoniae, 8 (18%) were Escherichia coli, 6 (13%) were Enterobacter cloacae, and 3 (7%) were Serratia marcescens. Multivariate logistic regression analysis showed that the only independent risk factor associated with infection by ESBL-producing strains was use of broad-spectrum cephalosporins. None of the isolates was resistant to imipenem. The bla_SHV5 gene was detected in 84% of isolates, followed by bla_CTX-M15 (27%), bla_SHV2 (9%), and bla_SHV12 (7%). PFGE identified six clones among the 28 ESBL-producing K. pneumoniae isolates. Conclusions: ESBL-producing K. pneumoniae clones were detected throughout the hospital. Use of broad-spectrum cephalosporins is the most important risk factor associated with the proliferation of ESBL-producing strains.

Increased Risk of Childhood Asthma From Antibiotic Use in Early Life

To address the major methodological issues of reverse causation and selection bias in epidemiologic studies of antibiotic use in early life and the development of asthma, we undertook a cohort study of this association in a complete population of children. Using the health-care and prescription databases of Manitoba, Canada, this longitudinal study assessed the association between antibiotic prescription use during the first year of life and asthma at age 7 years in a 1995 birth cohort of 13,116 children. Independent of well-known asthma risk factors, asthma was significantly more likely to develop in children who had received antibiotics in the first year of life at age 7 years. The association with asthma was observed for antibiotic use in non-respiratory tract infections (adjusted odds ratio [OR], 1.86; 95% confidence interval [CI], 1.02 to 3.37). The risk of asthma was highest in children receiving more than four courses of antibiotics (adjusted OR, 1.46; 95% CI, 1.14 to 1.88), especially among rural children, and in the absence of maternal asthma or a dog in the birth year. Broad-spectrum (BS) cephalosporin use was more common in these subpopulations of children. Antibiotic use in early life was associated with the development of childhood asthma, a risk that may be reduced by avoiding the use of BS cephalosporins.

Pharmacology Review

Cefepime is the only fourth-generation cephalosporin licensed for use in the United States. It is being used increasingly for treatment of infections caused by resistant gram-negative bacteria in older infants and children. Some hospitals have replaced antipseudomonal third-generation cephalosporin antibiotics (eg, ceftazidime) with cefepime because of high rates of infection caused by resistant gram-negative bacteria. Although cefepime generally is not used to treat infections in neonates, it is important for neonatologists to be familiar with the characteristics of the drug because there are a few circumstances in which cefepime may be appropriate therapy for an older infant hospitalized in a neonatal intensive care unit. It is important to understand the unique differences of the drug compared with older cephalosporins. The cephalosporin antibiotics are derivatives of cephalosporin C, a natural antibiotic derived from the fungus Emericellopsis minimum . Cephalosporins have a beta-lactam ring as their major structural component, and their spectrum of activity varies, depending on substitutions at the 3 and 7 positions of the cephalosporin nucleus. Traditionally, these antibiotics are grouped by their spectrum of activity against antimicrobial organisms (Table 1). First-generation cephalosporins are active against most gram-positive bacteria (except enterococci and Listeria ) and have limited activity against some gram-negative organisms. Second-generation cephalosporins have increased activity against gram-negative organisms. Cephamycins, which generally are classified with the second-generation cephalosporins, have enhanced activity against anaerobic bacteria. The third-generation cephalosporins have extended potency against gram-negative bacteria but are generally less active against susceptible staphylococci. Cefepime hydrochloride is a newer semisynthetic, broad-spectrum fourth-generation cephalosporin antibiotic. The other antibiotic in this class is cefpirome, which is not available for use in the United States. | | First Generation | Second Generation | Third Generation | Fourth Generation | |:----------:| ---------------- | ----------------- | ---------------- | ----------------- | | Oral | Cefadroxil | Cefaclor | Cefdinir | | | | Cephalexin | Cefprozil | Cefpodoxime | | | | Cephradine | Cefuroxime axetil | | | | | | Loracarbef | | | | Parenteral | Cefazolin | Cefamandole | Cefoperazone | Cefepime | | | Cephalothin | Cefuroxime | Cefotaxime | | | | Cephapirin | | Ceftizoxime | | | | | Cephamycins | Ceftriaxone | | | | | Cefotetan | Ceftazidime | | | | | Cefoxitin | | | Table 1. Generations of Cephalosporins Cefepime differs from the third-generation cephalosporins by having a quaternized N-methylpyrrolidine substitution at the C3 position of the cephem nucleus and an alkoxyimino group at the C7 position …

Most Enterobacter aerogenes strains in France belong to a prevalent clone.

The aim of this study was to determine the distribution in France of the Enterobacter aerogenes prevalent clone isolated in the hospitals of the Marseille area (A. Davin-Regli, D. Monnet, P. Saux, C. Bosi, R. Charrel, A. Barthelemy, and C. Bollet, J. Clin. Microbiol. 34:1474-1480, 1996). A total of 123 E. aerogenes isolates were collected from 23 hospital laboratories and analyzed by random amplification of polymorphic DNA and enterobacterial repetitive intergenic consensus-PCR to determine their epidemiological relatedness. Molecular typing revealed that 21 of the 23 laboratories had isolated this prevalent clone harboring the plasmid encoding for extended-spectrum beta-lactamase of the TEM-24 type. Most isolates were susceptible only to imipenem and gentamicin. Their dissemination seems to be clonal and was probably the result of the general use of broad-spectrum cephalosporins and quinolones. Four isolates showed an alteration of their outer membrane proteins, causing decrease of susceptibility to third-generation cephalosporins and imipenem and leading to the critical situation of having no alternative therapeutic. The large dissemination of the E. aerogenes prevalent clone probably results from its good adaptation to the antibiotics administered in France and the hospital environment, particularly in intensive care units.

Resistance to second- and third-generation cephalosporins among Escherichia coli and Klebsiella species is rare in Finland

OBJECTIVE: To investigate the antimicrobial resistance of Escherichia coli and Klebsiella spp. from pus, urine and respiratory specimens, with particular emphasis on the detection of third-generation cephalosporin resistance. METHODS: E. coli (698) and Klebsiella sp. (476) strains from pus, respiratory and urinary specimens from hospital patients were collected from 19 laboratories. Data about consumption of third-generation cephalosporins and cefuroxime were collected from 24 hospitals. Antimicrobial susceptibility was tested with disk diffusion in primary laboratories and by an agar dilution method. Extended-spectrum beta-lactamase (ESBL) production was studied with a double disk synergy test and an ESBL Etest. The beta-lactamase classes were characterized with polymerase chain reaction probes of the TEM and SHV beta-lactamase families and isoelectric focusing. RESULTS: Only 0.6% of E. coli and 2.3% of Klebsiella spp. strains were resistant or intermediately resistant to cefotaxime, ceftriaxone and/or ceftazidime. The ESBL producers detected comprised one E. coli harboring TEM-like genes and five Klebsiella pneumoniae strains, two of which harbored SHV-like genes, two TEM-like genes and one both. Although consumption of cefuroxime has increased in the years 1990-1994, from 3.48 to 5.84 defined daily doses/100 bed-days, and the consumption of third-generation cephalosporins from 1.25 to 1.94 defined daily doses/100 bed-days, cefuroxime resistance of E. coli was only 3%. CONCLUSION: Although the use of broad-spectrum cephalosporins has increased, resistance to second- and third-generation cephalosporins is still rare in Finland.

Clostridium difficile-associated diarrhoea: epidemiological data from Western Australia

The incidence of Clostridium difficile-associated diarrhoea (CDAD) was investigated retrospectively at a 690-bed teaching hospital for the period 1983-92. Our aims were to determine: (i) the distribution by age and sex of patients with CDAD, (ii) the possibility of a seasonal trend and, (iii) the influence of infection control procedures, contamination of the hospital environment and the use of third-generation cephalosporins. The laboratory diagnosis of CDAD was based on demonstration of the organism by stool culture and/or detection of specific cytotoxin in stool filtrates. C. difficile was detected in 917 patients who were being investigated for diarrhoeal illness. Yearly isolations varied from a low of 49 in 1983 to a high of 120 in 1990 (Chi square for linear trend 128.8; P < 0.005). Most patients were elderly, with 63% aged 60 years or more; the majority (59%) were female. The relationship between culture of C. difficile and detection of cytotoxin in faecal extracts was also examined. Sixty percent of a sample of 132 isolates from patients in whom faecal cytotoxin was not detected produced cytotoxin in vitro, suggesting that culture is a more sensitive indicator of infection with C. difficile than cytotoxin detection. When the total number of faecal specimens received in the laboratory was used as a denominator there was an increase in the number of incident cases of CDAD between 1983 and 1990, apart from 1986. When occupied bed days was used as the denominator a similar trend was observed with a peak in 1990.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative susceptibility patterns of common clinical isolates to cefoperazone: 1981 to 1987

It has been postulated that the widespread use of broad-spectrum cephalosporins might lead to increased bacterial resistance to such agents. To determine if such increased resistance to cefoperazone might be detectable, the susceptibility patterns of common clinical isolates to cefoperazone were examined from the Pathology Laboratories at Baptist Medical Center, Jacksonville, Florida, from 1981, prior to approval by the Food and Drug Administration, to the present. Gram-negative aerobic and facultative anaerobic organisms, staphylococci, and members of the Bacteroides fragilis group were included in the analysis. The data obtained were compared with results of similar published studies nationwide. No significant decrease in susceptibility to cefoperazone was detected for any gram-negative species examined. A steady increase in the percentage of staphylococci (both coagulase positive and especially coagulase negative) resistant to cefoperazone was demonstrable at this institution. This was a direct function of the concomitant rise in the percentages of staphylococci resistant to methicillin observed over the testing interval. Anaerobic susceptibility patterns of the members of the B. fragilis group were also relatively constant during this period of time. The concentrations of antibiotic inhibiting 50 percent (MIC 50) and 90 percent (MIC 90) of B. fragilis isolates as determined by an agar dilution technique were 16 μg/ml and 64 μg/ml, respectively, both in 1981 and in 1987. No change in the national susceptibility patterns of common bacterial isolates to cefoperazone was demonstrable in the five-year period during which the antibiotic has been available for clinical use.