Amikacin (BBK8) in Infections Due to Gram-Negative Organisms in Children over the Age of One Month

1976 ◽  
Vol 4 (1) ◽  
pp. 1-14 ◽  
Author(s):  
J I Ramirez ◽  
H Trujillo ◽  
A Uribe ◽  
Nancy H Agudelo ◽  
Esther Luisa de Vidal

Thirty children over the age of one month were treated with amikacin ( BBK8), a new aminoglycoside derived from kanamycin A, with three intramuscular dosage schedules. Each group consisted of ten patients. The first received 7.5 mg/kg/12 hours, the second 7.5 mg/kg/24 hours and the third, 3.75 mg/kg/12 hours. The infections and the bacteria were similar in all three groups: pyelonephritis, abscesses of soft tissues, infected wounds, septicaemia, superinfected empyema, gastro-enteritis, chronic otitis media; the bacteria were E. coli, Klebsiella, Pseudomonas and Salmonella. A were sensitive by the Kirby-Bauer method, although two were resistant by dilution in Petri dish. Of the thirty patients, twenty four (80%) were cured. The schedule of 3.75 mg/kg/12 hours was as effective as the schedule of7.5 mg/kg/12 hours for infections such as pyelonephritis, superficial abcesses, contaminated wounds, gastro-enteritis and sepsis. The cases with infections localized in rather unaccessible sites required double the dose and strict drainage and cleanliness. Plasma levels with the administration of 3.75 mg/kg fluctuated between 8.3 and 12.6 mcg/ml; with 7.5 mg/kg they fluctuated between 8.6 and 13.1. The minimum inhibitory level ( MIL) for the majority of the bacteria was 1.25 mcg/ml. No toxic reactions were observed.

2015 ◽  
Vol 53 (4) ◽  
pp. 1183-1191 ◽  
Author(s):  
James C. Hurley ◽  
Piotr Nowak ◽  
Lars Öhrmalm ◽  
Charalambos Gogos ◽  
Apostolos Armaganidis ◽  
...  

The clinical significance of endotoxin detection in blood has been evaluated for a broad range of patient groups in over 40 studies published over 4 decades. The influences of Gram-negative (GN) bacteremia species type and patient inclusion criteria on endotoxemia detection rates in published studies remain unclear. Studies were identified after a literature search and manual reviews of article bibliographies, together with a direct approach to authors of potentially eligible studies for data clarifications. The concordance between GN bacteremia and endotoxemia expressed as the summary diagnostic odds ratios (DORs) was derived for three GN bacteremia categories across eligible studies by using a hierarchical summary receiver operating characteristic (HSROC) method. Forty-two studies met broad inclusion criteria, with between 2 and 173 GN bacteremias in each study. Among all 42 studies, the DORs (95% confidence interval) were 3.2 (1.7 to 6.0) and 5.8 (2.4 to 13.7) in association with GN bacteremias withEscherichia coliand those withPseudomonas aeruginosa, respectively. Among 12 studies of patients with sepsis, the proportion of endotoxemia positivity (95% confidence interval) among patients withP. aeruginosabacteremia (69% [57 to 79%];P= 0.004) or withProteusbacteremia (76% [51 to 91%];P= 0.04) was significantly higher than that among patients without GN bacteremia (49% [33 to 64%]), but this was not so for patients bacteremic withE. coli(57% [40 to 73%];P= 0.55). Among studies of the sepsis patient group, the concordance of endotoxemia with GN bacteremia was surprisingly weak, especially forE. coliGN bacteremia.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Angela Borg Cauchi ◽  
Maria Angela Gauci ◽  
Theresia Dalli ◽  
James Gauci ◽  
James Farrugia ◽  
...  

Abstract Background and Aims Infections related to peritoneal dialysis (PD) are still a cause of morbidity and mortality. We describe an overview of PD peritonitis and catheter-related infections (CRI) in Malta over a period of eleven years. We also describe trends in dialysis modality over the years. Method All patients undergoing PD in Malta during 2008 and 2018 were analysed. Data from 2008-2012 was retrospective, shown as mean, that from 2013-2018 prospective. International Society for Peritoneal Dialysis (ISPD) definitions were used. Results for categorical responses were summarized using absolute numbers and percentages. Medians (range) were used to describe continuous non-normally distributed data. Results The total number of patients undergoing PD from 2008 till 2018 were 137 (2008-2012), 91, 80, 126, 117, 102, 103 respectively. There was an overall male predominance of 63.5% (61-67). Patient years at risk were 85.80, 85.25, 89.71, 83.70, 79.69, 72.88 since 2013 respectively. The overall incidence of diabetes mellitus was 45.3% (41.8-50), cardiovascular disease 34.2% (33.8-35), hypertension 79.3% (73.8-84.6). PD was used in 50% of dialysis modality prior to 2012, 39% in 2018. Initially 51% used Automated PD (APD), with 21% assisted PD, in 2018 39% used APD, with 6% assisted PD. PD peritonitis rates from 2008 were 0.38, 0.31, 0.35, 0.46, 0.43, 0.57, 0.54, 0.43, 0.39, 0.40, 0.46 episodes/patient year respectively There was marked dominance of Gram-positive peritonitis, mainly Staphylococcal, with a reduction of coagulase-negative-Staphylococcus from 0.26 episodes/patient in 2013 to 0.03 in 2017, 0.11 in 2018. Methicillin-resistant S. aureus (MRSA) peritonitis decreased from 0.03 episodes/patient to nil in 2016, 2017, 0.01 episodes/patient in 2018. Amongst Gram-negative peritonitis, Pseudomonas rates decreased from 0.06 to 0.03 episodes/patient in 2018, nil in 2016. Escherichia coli rates decreased from 0.02 episodes/patient to nil in the last three years. Fungal rates from 0.03 to 0.01 episodes/patient/year, with nil in 2016, 2017. Catheter-related infection rates were 0.39 (2008-2012), 0.35, 0.91, 0.37, 0.38, 0.25, 0.50 episodes/patient/year respectively. There was a higher incidence of recurrent infections in 2014, none in 2015 and 2016. Gram-negative organisms accounted for 57% of all CRI, predominantly Pseudomonas at 0.12 (2008-2012), 0.06, 0.09, 0.09, 0.14, 0.03, 017 episodes/patient/year respectively. Gram-positive CRI were mostly Staphylococcus aureus, peaking in 2014 at 0.38 episodes/patient/year. MRSA rates declined from 0.15 to 0.01 episodes/patient/year in 2018. Conclusion PD peritonitis rates in Malta between 2008 and 2018 were below the ISPD recommended threshold. There were no episodes of MRSA in 2016, 2017, no Pseudomonas in 2016, no E coli in the last three years and no fungal PD peritonitis in 2016, 2017. CRI rates also declined, with an overall predominance of Gram-negative infections.


2009 ◽  
Vol 55 (5) ◽  
pp. 627-632 ◽  
Author(s):  
Thomas Candela ◽  
Marie Moya ◽  
Michel Haustant ◽  
Agnès Fouet

Poly-γ-glutamate has been described in many Gram-positive organisms. When anchored to the surface, it is a capsule and as such a virulence factor. Based on sequence similarities, few Gram-negative organisms have been suggested to synthesize poly-γ-glutamate. For the first time, a Gram-negative bacterium, Fusobacterium nucleatum , is shown to produce and secrete poly-γ-glutamate. Putative poly-γ-glutamate-synthesizing genes from Gram-negative organisms have been compared with their Gram-positive homologs by in silico analysis, i.e., gene sequence and phylogenetic analysis. Clusters of three instead of four genes were highlighted by our screen. The products of the first two genes display similarity with their Gram-positive equivalents, yet the sequences from the Gram-negative organisms can be distinguished from those of the Gram-positives. Interestingly, the sequence of the predicted product of the third gene is conserved among Gram-negative bacteria but displays no similarity to that of either the third or fourth gene of the Gram-positive operons. It is suggested that, like for Gram-positive bacteria, poly-γ-glutamate has a role in virulence for pathogens and one in survival for other Gram-negative bacteria.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S755-S755 ◽  
Author(s):  
Helio S Sader ◽  
Cecilia G Carvalhaes ◽  
Rodrigo E Mendes ◽  
Mariana Castanheira ◽  
Robert K Flamm

Abstract Background Zidebactam (ZID) is a bicyclo-acyl hydrazide antibiotic with a dual mechanism of action: selective Gram-negative PBP2 binding and β-lactamase inhibition. We evaluated the frequency and antimicrobial susceptibility (S) of Gram-negative bacilli (GNB) isolated from patients with pneumonia in US hospitals. Methods All 3,086 clinical isolates were consecutively collected from patients hospitalized with pneumonia (1/patient) in 29 US medical centers in 2018, and the GNB (n = 2,171) were S tested against cefepime (FEP)-ZID (1:1 ratio) and comparators by reference broth microdilution methods. The FEP S breakpoint of ≤8 mg/L (CLSI, high dose) was applied to FEP-ZID for comparison purposes. An FEP-ZID S breakpoint of ≤64 mg/L has been proposed for non-fermentative GNB based on pharmacokinetic/pharmacodynamic target attainment and was applied. Enterobacterales (ENT) isolateswere screened for β-lactamase genes by whole-genome sequencing. Results GNB represented 70.3% of the collection, and the most common GNB were P. aeruginosa (PSA; 34.9% of GNB), K. pneumoniae (10.9%), E. coli (9.7%), S. marcescens (7.7%), and S. maltophilia (XM; 6.4%). FEP-ZID was highly active against PSA (MIC50/90, 2/8 mg/L; 98.8% and 99.9% inhibited at ≤8 and ≤16 mg/L, respectively; highest MIC, 32 mg/L), including resistant subsets (table). Among comparators, colistin (99.6%S), ceftazidime–avibactam (CAZ-AVI; 95.2%S), and ceftolozane–tazobactam (C-T; 94.5%S) were the most active compounds against PSA. FEP-ZID inhibited all ENT at ≤4 mg/L, including ESBL-producers (MIC90, 0.25 mg/L) and carbapenem-resistant ENT (MIC90, 4 mg/L). The most active comparators against ENT were CAZ-AVI (99.9%S), amikacin (98.5%S), and meropenem (MEM; 98.3%S). FEP-ZID inhibited 75.0% and 97.9% of XM isolates at ≤8 and ≤16 mg/L, respectively (highest MIC, 64 mg/L). The only other compounds active against XM were co-trimoxazole (MIC50/90, ≤0.12/2 mg/L; 95.7%S) and levofloxacin (MIC50/90, 1/2 mg/L; 70.7%S). FEP-ZID inhibited 71.0% and 98.9% of A. baumannii isolates at ≤8 and ≤64 mg/L,, respectively. Conclusion FEP-ZID showed potent in vitro activity against GNB causing pneumonia in US hospitals and may represent a valuable therapeutic option for these difficult-to-treat infections Disclosures All authors: No reported disclosures.


2018 ◽  
Vol 39 (12) ◽  
pp. 1419-1424 ◽  
Author(s):  
Rachael A. Lee ◽  
Morgan C. Scully ◽  
Bernard C. Camins ◽  
Russell L. Griffin ◽  
Danielle F. Kunz ◽  
...  

AbstractObjectiveDue to concerns over increasing fluoroquinolone (FQ) resistance among gram-negative organisms, our stewardship program implemented a preauthorization use policy. The goal of this study was to assess the relationship between hospital FQ use and antibiotic resistance.DesignRetrospective cohort.SettingLarge academic medical center.MethodsWe performed a retrospective analysis of FQ susceptibility of hospital isolates for 5 common gram-negative bacteria: Acinetobacter spp., Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Primary endpoint was the change of FQ susceptibility. A Poisson regression model was used to calculate the rate of change between the preintervention period (1998–2005) and the postimplementation period (2006–2016).ResultsLarge rates of decline of FQ susceptibility began in 1998, particularly among P. aeruginosa, Acinetobacter spp., and E. cloacae. Our FQ restriction policy improved FQ use from 173 days of therapy (DOT) per 1,000 patient days to <60 DOT per 1,000 patient days. Fluoroquinolone susceptibility increased for Acinetobacter spp. (rate ratio [RR], 1.038; 95% confidence interval [CI], 1.005–1.072), E. cloacae (RR, 1.028; 95% CI, 1.013–1.044), and P. aeruginosa (RR, 1.013; 95% CI, 1.006–1.020). No significant change in susceptibility was detected for K. pneumoniae (RR, 1.002; 95% CI, 0.996–1.008), and the susceptibility for E. coli continued to decline, although the decline was not as steep (RR, 0.981; 95% CI, 0.975–0.987).ConclusionsA stewardship-driven FQ restriction program stopped overall declining FQ susceptibility rates for all species except E. coli. For 3 species (ie, Acinetobacter spp, E. cloacae, and P. aeruginosa), susceptibility rates improved after implementation, and this improvement has been sustained over a 10-year period.


PEDIATRICS ◽  
1996 ◽  
Vol 97 (5) ◽  
pp. 739-741
Author(s):  
Lynne M. Bird ◽  
Marilyn C. Jones ◽  
Nathan Kuppermann ◽  
W. Charles Huskins

Klippel-Trenaunay-Weber syndrome (KTWS) is a sporadically occurring congenital malformation syndrome consisting of hemangiomata, venous varicosities, and hypertrophy of soft tissues and/or overgrowth of bone.1-3 Although the list of potential complications is long, KTWS is generally a nonprogressive condition. The problems, which include edema, stasis dermatitis, skin ulceration, cellulitis, anemia, thrombosis, phleboliths, phlebitis, bone and joint abnormalities, scoliosis, and paresthesias, tend to be chronic in nature.4 Recognized life-threatening complications include disseminated intravascular coagulation (DIC)5 and gastrointestinal bleeding as a result of hemangiomata in the intestine.6,7 Systemic infection has not been reported as a major cause of morbidity and mortality. The purpose of this report is to present 4 patients with KTWS who had invasive infection with gram-negative organisms to document another life-threatening complication of this syndrome.


1980 ◽  
Vol 75 (1-2) ◽  
pp. 161-172 ◽  
Author(s):  
Heonir Rocha ◽  
Vanete S. Oliveira ◽  
Moema Magnavita G. de Oliveira

Animals (122 mice) were infected each with eighty cercariae of S. mansoni and subsequently challenged intravenously eight weeks later with the following gram-negative organisms. S. typhi, E. coli, Klebsiella-enterobacter species, Proteus mirabilis and Pseudomonas aeruginosa. Enumeration of bacteria in the liver, spleen and blood and S. mansoni from the portal sistem was performed from one to four weeks later in infected animals. A significant difference between infection produced by S. typhi and other gram negative organisms was observed: S. typhi persisted longer in the spleen and liver and could be recovered from S. mansoni worms up to three weeks following bacterial infection. Other gram negative bacteria disappeared from S. mansoni worms after two weeks of initial challenge. Additional animals (51 mice) infected with S. mansoni were given S. typhi, E. coli or sterile saline. After two weeks, animals were sacrificed and the recovery rate of worms from the portal system, and the mesenteric and hepatic oogram were determined. in animals infected with E. coli a significant decrease in the number of worms was observed compared to the saline control group; thirty worms were recovered in the control group compared to two worms in e. coli infected animals. In addition, the patterns of oviposition was significantly different in these latter animals suggesting complete inhibition of this process. Following S. typhi infection the difference in recovery of worms and pattern of oviposition was minimal. These findings suggest a difference in the interaction of various gram negative bacteria and S. mansoni and are consistent with the clinical observation of prolonged salmonella bacteremia in patients with schistosomiasis.


1983 ◽  
Vol 11 (2) ◽  
pp. 113-115 ◽  
Author(s):  
Ingemar Helin

In a prospective study, twenty children with a mean age of 4 years were treated with pivmecillinam, 25 mg to 40 mg per kilogram body-weight and day, for acute pyelonephritis. Urine cultures yielded growth of E. coli in sixteen instances, Klebsiella spp. in two, S. saprophyticus in one and a mixed Gram-positive flora in one patient. All children fulfilled the diagnostic criteria for upper urinary tract infection. In all cases where Gram-negative pathogens were responsible, the infections were eradicated. One reinfection was registered in a child with a concomitantly discovered congenital urological malformation. Pivmecillinam also cured one patient infected with S. saprophyticus but was ineffective in the case of mixed Gram-positive flora. It is concluded that pivmecillinam is a valuable new drug for the management of pyelonephritis in children, as most of these infections are caused by Gram-negative organisms.


1992 ◽  
Vol 106 (2) ◽  
pp. 173-177 ◽  
Author(s):  
A. G. Douglas-Jones ◽  
C. Rodd ◽  
E. M. V. James ◽  
R. G. S. Mills

AbstractMalakoplakia presenting in the head and neck is very rare. We present a case of an inflammatory mass in the neck, clinically mimicking actinomycosis in a 67-year-old man. Repeated culture of E. coli and histological and electron microscopic examination of biopsy material showed an infiltration of granular macrophages and intracellular gram negative bacilli, but no classical Michaelis-Gutmann bodies. The clinical and pathological findings and criteria for the diagnosis of malakoplakia are discussed.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S65-S66
Author(s):  
Kenneth Klinker ◽  
Karri A Bauer ◽  
C Andrew DeRyke ◽  
Levita K Hidayat

Abstract Background A primary tenet of antimicrobial stewardship programs (ASPs) is to establish empiric antibiotic treatment recommendations. While traditional antibiograms are useful, intrinsic variability in susceptibility exists when stratifying by source and/or location. In contrast, a syndromic antibiogram displays the likelihood of adequate coverage for a specific infection syndrome, considering the weighted incidence of pathogens causing that syndrome. The aim of the study was to compare antibiotic susceptibilities using a traditional versus syndromic antibiogram. Methods Between 2016–2019, 20 US institutions per year submitted up to 250 consecutive targeted gram-negative pathogens from hospitalized patients as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART). MICs were determined by broth microdilution and interpreted using 2020 CLSI breakpoints, except for imipenem/relebactam (I/R) for which FDA breakpoints were used. The traditional antibiogram included the 3 most common Gram-negative pathogens from all sources and represented critical organisms considered for empiric antibiotic coverage; the syndromic antibiogram included the 3 most commonly isolated Gram-negative pathogens from a respiratory source based on patient location. Results 17,561 Gram-negative isolates, including 6,654 lower respiratory isolates were evaluated. The top 3 most common Gram-negative organisms included: E. coli (n=6095, 44%), Klebsiella spp. (n=4097, 30%), P. aeruginosa (n=3649, 26%). Cumulative susceptibilities were comparable using a traditional vs. syndromic antibiogram (Figure 1); however, cefepime (FEP), piperacillin/tazobactam (TZP), and meropenem (MEM) susceptibilities were 5 – 8% lower when stratified by patient location (Figure 2) and ≥10% for P. aeruginosa (Figure 3). Ceftolozane/tazobactam (C/T) and I/R demonstrated ≥90% susceptibility regardless of respiratory source or patient location. Figure 1. Cumulative susceptibility of E. coli, Klebsiella spp, and P. aeruginosa for traditional vs. syndromic antibiogram Figure 2. Syndromic antibiogram evaluating cumulative susceptibility of E. coli (n = 637), Klebsiella spp. (n = 1190) and P. aeruginosa (n = 1997) respiratory isolates stratified by patient location Figure 3. Syndromic antibiogram evaluating susceptibility of P. aeruginosa (n = 1997) respiratory isolates stratified by patient location Conclusion Our analysis demonstrated that susceptibilities were lower for first-line agents when stratified by ICU and P. aeruginosa. ASPs should consider syndromic antibiograms based on source and patient location to optimize empiric antibiotic therapy recommendations. Disclosures Kenneth Klinker, PharmD, Merck & Co, Inc (Employee) Karri A. Bauer, PharmD, Merck Research Laboratories (Employee) C. Andrew DeRyke, PharmD, Merck & Co., Inc. (Employee, Shareholder) Levita K. Hidayat, PharmD BCIDP, Merck & Co (Employee)


Sign in / Sign up

Export Citation Format

Share Document