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Background: Pseudomonas aeruginosa are known for their multiple mutations and rapid acquirement of antimicrobial resistance genes. The presence of metallo-?-lactamase (MBL) is the commonest reason for the treatment failure in carbapenem therapy. Production of extended spectrum ?-lactamase (ESBL) in these isolates makes the treatment more challenging. Due to the importance of the carbapenems in resistant infection management, finding the true frequencies of such enzymes is imperative. Methods: A total of 446 samples were collected from the admitted patients with infected burn, surgical wound, and endotracheal tube in situ. Isolation and identification of organisms and antimicrobial susceptibility testing were done by established methods. Identification of P. aeruginosa was confirmed by polymerase chain reaction (PCR). Production of ESBLs was detected phenotypically by double disc synergy, and MBL by double-disc synergy, combined disc, and modified Hodge test. Genes encoding ESBLs and MBLs were detected by PCR. Results: Among the 446 samples, 84.31% yielded growth, from which 232 (61.70%) were P. aeruginosa. Among the P. aeruginosa, 72 (31.03%) were resistant to imipenem. Phenotypically, 57 (79.17%) of these strains were ESBL and all were MBL producers. blaOXA-10 was the most common ESBL encoding gene (29.83%). blaNDM-1 was the most prevalent MBL encoding gene (34.72%). Moreover, 27 (38%) imipenem resistant P. aeruginosa had concurring ESBL and MBL genes.
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Objective:To establish a rapid method to detect the minimum inhibitory concentration (MIC) of imipenem in Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) based on ompK36 gene′s GD mutation. Methods:This was a methodological evaluation study. A total of 258 isolates of Klebsiella pneumoniae were collected from Lishui Municipal Central Hospital from March 2011 to December 2019. Porin gene ompK36 and carbapenemase genes blaKPC, blaNDM, blaIMP and blaOXA-48 were amplified by PCR and confirmed by sequencing. The MIC was detected and confirmed by microbroth dilution susceptibility test, and the corresponding patterns of genotype and MIC were constructed. Based on the patterns, a method for rapid detection of imipenem MIC by real-time fluorescence PCR (RT-PCR) was designed and established. The 159 isolates of non-repetitive Klebsiella pneumoniae collected by Lishui Disease Prevention and Control Center (CDC) from 2017 to 2019 were used for further verification. The sensitivity and specificity were calculated by fourfold table. Kappa test was used to compare the consistency between RT-PCR and microbroth dilution susceptibility test. Results:Among 258 isolates, 109 isolates did not carry carbapenemase gene, 65 isolates carried ompK36 gene GD mutation, 127 isolates carried blaKPC, 15 isolates carried blaNDM, 9 isolates carried blaIMP, and blaOXA-48 was not detected. With mircobroth dilution susceptibility test as the standard, there were 3 corresponding patterns between the drug resistance gene and the imipenem MIC of Kp: when all the 4 carbapenemase genes were negative, MIC≤1 mg/L, the sensitivity was 100% (107/107) and the specificity was 98.4% (125/127); when blaKPC was positive and ompK36 gene GD mutation was negative, 4 mg/L≤MIC≤16 mg/L, the sensitivity was 88.2% (60/68) and the specificity was 98.8% (164/166); when blaKPC and ompK36 gene GD mutation were both positive, MIC≥32 mg/L, the sensitivity was 96.6% (57/59) and the specificity was 96.6% (169/175). RT-PCR detected blaKPC, blaNDM, blaIMP, blaOXA-48 genes accurately.The RT-PCR results of ompK36 gene GD mutation in the KPC-producing isolates were 100% consistent with the sequencing results. In the 159 isolates from Lishui CDC, the sensitivity and specificity of imipenem MIC detected by RT-PCR were higher than 95% in all 3 patterns with mircobroth dilution susceptibility test as the standard, and Kappa value was 0.971. Conclusion:The RT-PCR based on ompK36 gene GD mutation was helpful to quickly determine the MIC range of imipenem in KPC-Kp.
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OBJECTIVE To establish a UPLC-MS/MS method for the determination of plasma concentration of three carbapenem antibiotics， i.e. ertapenem （ETP）， imipenem （IPM） and meropenem （MEM）. METHODS After protein precipitation with methanol， the plasma samples were separated by ACQUITY UPLC BEH C18 column （2.1 mm×50 mm， 1.7 μm） using stable isotopes of three antibiotics （ETP-D4， IPM-D4， MEM-D6） as the internal standard. The mobile phases were 98% acetonitrile +2% water +0.1% formic acid and 98% water +2% acetonitrile +0.1% formic acid， by gradient elution. The flow rate was 0.3 mL/min and the column temperature was 40 ℃. Scanning analysis was performed in the positive ion and multiple reaction monitoring mode. RESULTS The method had good specificity， good linearity （r2≥0.993） in the range of 0.2-200， 0.1-100 and 0.1-100 μg/mL of ETP， IPM and MEM， and good intra-batch and inter-batch precision and accuracy （all RE≤5.14%， all RSD≤11.15%）， the matrix effect and extraction recovery were consistent （RSD≤12.99%）. CONCLUSIONS This study establishes the UPLC-MS/MS method to simultaneously quantify the plasma concentration of ETP， IPM and MEM. The method has the advantages of simple pretreatment， short detection time and small sample quantity to meet clinical requirement.
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Objective Combined with domestic and foreign guidelines,to explore the individualized treatment strategy of urosepsis,and to provide reference for standardized diagnosis and treatment of urosepsis patient.Methods To analyze the diagnosis and treatment process of a patient with urogenic sepsis who was admitted to the department of critical care medicine of the First Affiliated Hospital of Xi'an Jiaotong University in April 15,2021.During the diagnosis and treatment process,we performed puncture drainage fluid and urine culture as soon as possible to confirm the diagnosis from the perspective of etiology.Considering the possible pathogenic bacteria at the infection site,the drug resistance of pathogenic bacteria in medical units,and drug safety,imipenem and cilastatin was chosen for anti-infective therapy.A two-step approach was used for drug administration based on drug pharmacokinetics/pharmacodynamic(PK/PD)characteristics,and drug concentration monitoring.The patients were followed up after discharge.Results The patient was critically ill on admission and was diagnosed with urosepsis.We optimize the empirical use of antimicrobials based on their PK/PD characteristics.Ultrasound-guided percutaneous nephrostomy of the left renal pelvis was performed to adequately drain the infection.Urine culture returned as extended-spectrum β-lactamase(ESBL)-producing Escherichia coli,confirming the etiological diagnosis.After 7 days of treatment,the patient's condition improved,the antibacterial drugs were downgraded to piperacillin-tazobactam,and the total course of anti-infection was 14 days.The patient was in good condition 2 months after discharge,and underwent left ureteral calculus and lithotripsy in the local hospital,and the left nephrostomy tube was removed.After discharge,the patient's condition was stable,no recurrence was found after 7 months of follow-up,and daily life was not affected.Conclusions Management of infection foci in urosepsis patient is critical.Diagnosis and treatment should refer to domestic and foreign guidelines,and formulate treatment strategies based on the distribution of local pathogens,drug resistance,and the actual clinical conditions of patients.Optimize the use of antibiotics based on drug PK/PD characteristics,monitor the concentration of therapeutic drugs,and realize individualized treatment.
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Objective:Machine learning is not only an important branch of artificial intelligence, but also supporting technologies for bioinformatics analysis. In the presence work, four machine-learning-predictive model for the drug-sensitivity of Klebsiella pneumoniae to imipenem were established based on matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and the diagnostic effect of these methods was exmained. Methods:A retrospective study was performed and the data of MALDI-TOF-MS and imipenem sensitivity of a total number of 684 cases Klebsiella pneumoniae isolated from clinical specimens in the laboratory of microbiology department of Tianjin Haihe Hospital from 2019 January to 2020 December were collected. The mass spectrometry and imipenem sensitivity data of 70 cases identified as imipenem-sensitive and 70 resistant cases were simple randomly selected to establish the training set model; whereas 30 cases of sensitive and 30 cases of resistant cases were randomly selected to establish the test set model. Mass spectral peak data were subjected to Orthogonal Partial least squares Discriminant Analysis (OPLS-DA). The training set data model was established by machine learning least absolute shrinkage and selection operator (LASSO) algorithm, Logistic Regression (LR) algorithm, Support vector machines (SVM) algorithm, neural network (NN) algorithm. The area under the curve (AUC) and confusion matrix of training set and test set model were calculated and selected by Grid search and 10-fold Cross-validation respectively, the accuracy of the prediction model was verified by test set confusion matrix. Results:The R2Y and Q2 of OPLS-DA were 0.546 3 and 0.017 8. The AUC of the best training set and test set models were 1.000 0 and 0.858 1, 1.000 0 and 0.820 1, 0.940 8 and 0.756 1, 1.000 0 and 0.697 2 evaluated by LASSO, LR, SVM and NN model respectively. The accuracy of the model were 99% (69/70), 100% (70/70), 91% (64/70) and 100% (70/70) for prediction of drug resistance, 100% (70/70), 100% (70/70), 90% (63/70) and 100% (70/70) for drug sensitivity prediction, the correct rate were 99% (139/140), 100% (140/140), 91% (127/140) and 100% (140/140) in training set, the test set showed that the accuracy were 93% (28/30), 87% (26/30), 60% (18/30) and 60% (18/30) for prediction of drug resistance, 100% (30/30), 80% (24/30), 93% (28/30) and 67% (20/30) for drug sensitivity prediction, the correct rate were 97% (58/60), 83% (50/60), 77% (46/60) and 63% (38/60) by LASSO, LR, SVM and NN model respectively.Conclusion:The LASSO prediction model of Klebsiella pneumoniae sensitivity to imipenem established in this study has a high accuracy rate and has potential clinical decision support ability.
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Abstract Carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa are being isolated from patient specimens with increasing frequency in Latin America and worldwide. The current study provides an initial description of the in vitro activity of imipenem/relebactam (IMR) against non-Morganellaceae Enterobacterales (NME) and P. aeruginosa infecting hospitalized patients in Latin America. From 2018 to 2020, 37 clinical laboratories in nine Latin American countries participated in the SMART global surveillance program and contributed 15,466 NME and 3408 P aeruginosa isolates. MICs for IMR and seven comparators were determined using CLSI broth microdilution and interpreted by CLSI M100 (2022) breakpoints. β-lactamase genes were identified in selected isolate subsets. IMR (96.9% susceptible), amikacin (95.9%), meropenem (90.7%), and imipenem (88.7%) were the most active agents against NME. Among piperacillin/tazobactam-nonsusceptible NME (n= 4124), 90.4% of isolates were IMR-susceptible (range by country, 97.2 [Chile] to 67.0% [Guatemala]) and among meropenem-nonsusceptible NME isolates (n= 1433), 74.0% were IMR-susceptible (94.1% [Puerto Rico] to 5.1% [Guatemala]). Overall, 6.3% of all collected NME isolates carried a KPC (metallo-β-lactamase [MBL]-negative), 1.8% an MBL, 0.4% an OXA-48-like carbapenemase (MBL-negative), and 0.1% a GES carbapenemase (MBL-negative). Amikacin (85.2% susceptible) and IMR (80.1%) were the most active agents against P. aeruginosa; only 56.5% of isolates were imipenem-susceptible. Relebactam increased susceptibility to imipenem by 22.0% (from 23.9% to 45.9%) in piperacillin/tazobactam-nonsusceptible isolates (n= 1031) and by 35.5% (from 5.5% to 41.0%) in meropenem-nonsusceptible isolates (n= 1128). Overall, 7.6% of all collected P. aeruginosa isolates were MBL-positive and 0.7% carried a GES carbapenemase. In conclusion, in 2018‒2020, almost all NME (97%) and most P. aeruginosa(80%) isolates from Latin America were IMR-susceptible. Continued surveillance of the in vitro activities of IMR and comparator agents against Gram-negative pathogens, and monitoring for β-lactamase changes (in particular for increases in MBLs), is warranted.
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Purpose: Real?life comparison of three intravitreal drug regimens used in cases of endophthalmitis at a tertiary care center in India. Methods: In this prospective, comparative study, patients of bacterial endophthalmitis were grouped according to intravitreal antibiotic drug regimens into Group 1 (ceftazidime and vancomycin), Group 2 (piperacillin + tazobactam and vancomycin), and Group 3 (imipenem and vancomycin). Forty?eight hours after injection nonresponding/worsening patients underwent vitrectomy. Vitreous samples were subjected to microbiological and pharmacokinetic tests. Results: A total of 64 patients were included and divided into Group 1: 29, Group 2: 20, and Group 3: 15 cases. Also, 75% of patients were post?surgical endophthalmitis, whereas 25% were post?traumatic. Improvement in vision (V90?0) and vision at 3 months (V90) were comparable between the three groups. Visual recovery was poorer in post?traumatic cases. In post?surgical cases, visual recovery was poorer in those presenting beyond 72 h of onset of symptoms (P = 0.0002). Polymerase chain reaction (PCR) positivity (66%) was higher than BACTECTM (33%) and culture (14%). Antibiotic resistance was comparable amongst the three groups. Most patients (62/64) further underwent vitrectomy. Ceftazidime and vancomycin achieved vitreous concentrations more than the minimum inhibitory concentration (MIC) at 48 h after the first injection. Conclusion: The choice of antibiotics did not affect the rate of vitrectomy and final vision in a real?life scenario. Ceftazidime and vancomycin can still be used as first?line intravitreal antibiotics owing to their comparable microbial sensitivity profile and adequate ocular bioavailability
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Introduction: Carbapenem resistance due to metallo-beta-lactamase (MBL)-producing bacteria is an emerging threat worldwide. This study aimed to detect the MBL production in clinical isolates of E. coli and Klebsiella pneumoniae species in our hospital setting and to evaluate the efficiency of two phenotypic methods for the detection of MBL production. Materials and Methods: The present study was carried out in the Department of Microbiology, MGM Medical College and Hospital, Aurangabad, Maharashtra, for a period of 2 years from April 2018 to March 2020. From a total of 12,324 various clinical specimens, 393 isolates of E. coli and Klebsiella pneumoniae species were tested for MBL production. MBL was detected by two different phenotypic methods, i.e., combined disc test and E-test. Results: Out of 393 isolates, 130 (33.07%) isolates were resistant to imipenem on screening of which 71 (18.06%) were Klebsiella pneumoniae and 59 (15.01%) were E. coli. About 43.66% Klebsiella pneumoniae isolates and 40.67% E. coli isolates were MBL-positive by the combined disc test. Using the E-test, MBL production was found to be 46.47% and 45.76% in Klebsiella pneumoniae and E. coli, respectively. Conclusion: Routine screening of MBL-producing organisms should be performed in diagnostic laboratories to control the spread of resistance and for the proper management of antibiotic therapy. E-test is better than the combined disc test for the detection of MBL-producing gram-negative bacilli.
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SUMMARY OBJECTIVE: The aim of this study was to explore the efficacy of imipenem combined with glutamine in the treatment of severe acute pancreatitis with abdominal infection in mainland China using meta-analysis. METHODS: We searched China National Knowledge Network, Wanfang Medical Network, Chinese Science Citation Database, PubMed, and Embase Databases for publications of imipenem combined with glutamine in the treatment of severe acute pancreatitis abdominal infection. The search time limit was from the establishment of the database to April 10, 2021. Stata software version 12.0 was used for statistical analysis; the combined effect size odds ratio and standardized mean difference values were calculated for the count data and measurement data, respectively; and the heterogeneity test was performed in this study. RESULTS: A total of five randomized controlled trials were included. A total of 499 cases were included, with 251 in the observation group and 248 in the control group. Meta-analysis results showed that the efficacy of imipenem combined with glutamine in the treatment of severe acute pancreatitis with abdominal infection was significantly better than that of imipenem alone (odds ratio=0.78, 95%CI 0.71-0.86, p=0.040). CONCLUSION: Imipenem combined with glutamine can significantly improve the efficacy in the treatment of severe acute pancreatitis with abdominal cavity infection.
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ObjectiveTo screen out the extended spectrum beta-lactamase （ESBL）-producing Escherichia coli with the strongest biofilm-forming ability through experiments， and discuss the effect of modified Dayuansan （MDYS） combined with imipenem-cilastatin and cilastatin sodium on the biofilm of E. coli. MethodThe paper diffusion and crystal violet staining methods were used to identify 19 clinically isolated strains of drug-resistant E. coli-induced enzymes and the biofilm-forming ability. The induced enzymes and the E. coli with the strongest biofilm-forming ability were screened out. The minimum inhibitory concentration （MIC） value of MDYS and imipenem-cilastatin and cilastatin sodium was determined by 2，3-bis（2-methoxy-4-nitro-5-sulfophenyl）-2H-tetrazolium-5-carboxamide （XTT） assay. The 1/2， 1/4， and 1/8 MIC of the water extract of MDYS， imipenem-cilastatin and cilastatin sodium alone， and MDYS combined with imipenem-cilastatin and cilastatin sodium was determined by methyl thiazolyl tetrazolium （MTT） assay to obtain the optimum concentration of drugs. BioFlux dynamically observed the effect of the optimum combined drug concentration on the number of bacteria in the biofilm and the biofilm formation of E. coli， and observed the distribution of live/dead bacteria with a laser confocal scanning microscope. Finally， the morphological changes in bacteria after drug treatment were observed statically by scanning electron microscopy. ResultE5E7 strain was ESBL enzyme and the E. coli with the strongest biofilm-forming ability. The results of MTT assay showed that the MIC values of the water extracts of imipenem-cilastatin and cilastatin sodium and MDYS were 1 mg·L-1 and 250 g·L-1， respectively. The results of XTT assay showed that compared with the blank group， the 1/2， 1/4， and 1/8 MIC MDYS groups and the combined drug groups significantly decreased the number of bacteria in the biofilm （P<0.01）. The inhibitory effect diminished as the concentration of imipenem-cilastatin and cilastatin sodium decreased. Compared with the imipenem-cilastatin and cilastatin sodium group with the same concentration， the combined drug group improved the inhibitory effect on the number of bacteria in the biofilm （P<0.01）. Compared with the MDYS group with the same concentration， 1/2 MIC imipenem-cilastatin and cilastatin sodium combined with 1/2， 1/4， and 1/8 MIC MDYS， 1/4 MIC imipenem-cilastatin and cilastatin sodium combined with 1/2 and 1/4 MIC MDYS， and 1/8 MIC imipenem-cilastatin and cilastatin sodium combined with 1/2 and 1/4 MIC MDYS decreased the number of bacteria （P<0.05， P<0.01）. The results of BioFlux showed that compared with the blank group， the 1/2 and 1/8 MIC imipenem-cilastatin and cilastatin sodium groups had an insignificant effect on the area of biofilm， whereas the 1/2 and 1/4 MIC MDYS groups significantly decreased the area of biofilm. The results under the scanning electron microscopy showed that as compared with the blank group and the imipenem-cilastatin and cilastatin sodium group， the division cycle was significantly longer under the action of MDYS combined with imipenem-cilastatin and cilastatin sodium. The length of the division cycle in the combined drug group was higher than that in drug alone group. ConclusionIn vitro studies reveal that MDYS combined with commonly-used antibiotics can inhibit the biofilm status of multi-drug resistant E. coli， and MDYS has the effect of enhancing sensitization and inhibiting bacteria with synergistic antibiotics.
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ObjectiveTo screen out the extended spectrum beta-lactamase （ESBL）-producing Escherichia coli with the strongest biofilm-forming ability through experiments， and discuss the effect of modified Dayuansan （MDYS） combined with imipenem-cilastatin and cilastatin sodium on the biofilm of E. coli. MethodThe paper diffusion and crystal violet staining methods were used to identify 19 clinically isolated strains of drug-resistant E. coli-induced enzymes and the biofilm-forming ability. The induced enzymes and the E. coli with the strongest biofilm-forming ability were screened out. The minimum inhibitory concentration （MIC） value of MDYS and imipenem-cilastatin and cilastatin sodium was determined by 2，3-bis（2-methoxy-4-nitro-5-sulfophenyl）-2H-tetrazolium-5-carboxamide （XTT） assay. The 1/2， 1/4， and 1/8 MIC of the water extract of MDYS， imipenem-cilastatin and cilastatin sodium alone， and MDYS combined with imipenem-cilastatin and cilastatin sodium was determined by methyl thiazolyl tetrazolium （MTT） assay to obtain the optimum concentration of drugs. BioFlux dynamically observed the effect of the optimum combined drug concentration on the number of bacteria in the biofilm and the biofilm formation of E. coli， and observed the distribution of live/dead bacteria with a laser confocal scanning microscope. Finally， the morphological changes in bacteria after drug treatment were observed statically by scanning electron microscopy. ResultE5E7 strain was ESBL enzyme and the E. coli with the strongest biofilm-forming ability. The results of MTT assay showed that the MIC values of the water extracts of imipenem-cilastatin and cilastatin sodium and MDYS were 1 mg·L-1 and 250 g·L-1， respectively. The results of XTT assay showed that compared with the blank group， the 1/2， 1/4， and 1/8 MIC MDYS groups and the combined drug groups significantly decreased the number of bacteria in the biofilm （P<0.01）. The inhibitory effect diminished as the concentration of imipenem-cilastatin and cilastatin sodium decreased. Compared with the imipenem-cilastatin and cilastatin sodium group with the same concentration， the combined drug group improved the inhibitory effect on the number of bacteria in the biofilm （P<0.01）. Compared with the MDYS group with the same concentration， 1/2 MIC imipenem-cilastatin and cilastatin sodium combined with 1/2， 1/4， and 1/8 MIC MDYS， 1/4 MIC imipenem-cilastatin and cilastatin sodium combined with 1/2 and 1/4 MIC MDYS， and 1/8 MIC imipenem-cilastatin and cilastatin sodium combined with 1/2 and 1/4 MIC MDYS decreased the number of bacteria （P<0.05， P<0.01）. The results of BioFlux showed that compared with the blank group， the 1/2 and 1/8 MIC imipenem-cilastatin and cilastatin sodium groups had an insignificant effect on the area of biofilm， whereas the 1/2 and 1/4 MIC MDYS groups significantly decreased the area of biofilm. The results under the scanning electron microscopy showed that as compared with the blank group and the imipenem-cilastatin and cilastatin sodium group， the division cycle was significantly longer under the action of MDYS combined with imipenem-cilastatin and cilastatin sodium. The length of the division cycle in the combined drug group was higher than that in drug alone group. ConclusionIn vitro studies reveal that MDYS combined with commonly-used antibiotics can inhibit the biofilm status of multi-drug resistant E. coli， and MDYS has the effect of enhancing sensitization and inhibiting bacteria with synergistic antibiotics.
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Imipenem-cilastatin is a broad-spectrum carbapenem antibiotic drug that has been widely used in clinical practice ， but there is a lack of guidelines and expert consensus on the development of individualized regimens for special status populations [e.g. continuous renal replacement therapy （CRRT）patients，extracorporeal membrane oxygenation （ECMO）patients， critically ill burn patients ，neonates and children]. In this paper ，by searching population pharmacokinetics research of imipenem- cilastatin in special status populations ，it is recommended that imipenem-cilastatin is given 1 to 3 g/d for CRRT patients ；500 mg to 1 g，q6 h for burn patients ；750 mg to 1 g，q6 h for ECMO patients ；20 mg/kg or 25 mg/kg，q8 h for neonates ；and 25 mg/kg，q6 h for children.
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La pustulosis exantematosa generalizada aguda (PEGA) es una patología dermatológica poco frecuente, caracterizada por la aparición brusca y generalizada de múltiples pústulas puntiformes, estériles, no foliculares, sobre una base eritematosa y edematosa. Es desencadenada frecuentemente por fármacos, entre los cuales resaltan los antibióticos. Presentamos el caso de un paciente varón de 40 años, que ingresó a emergencia por síndrome doloroso abdominal a descartar patología tumoral intraabdominal, indicándole inicialmente ceftriaxona y metronidazol. Al día siguiente, reingresó a emergencia encontrando, tras la cirugía de emergencia, una apendicitis aguda complicada con perforación intestinal, por lo cual rotan la antibioticoterapia a imipenem-cilastatina + metronidazol. A las siguientes 48 horas, presentó eritema generalizado y algunas pústulas pequeñas y microvesículas en región torácica, extremidades superiores y cuello. Asimismo, se observó en los exámenes de laboratorio, leucocitosis neutrofílica e hipoalbuminemia. En la biopsia, se encontró pústulas neutrofílicas subcorneales e intraepidérmicas, con dermis papilar edematosa e infiltrado inflamatorio perivascular con presencia de neutrófilos y escasos eosinófilos. Con todo lo descrito anteriormente, llegamos a la conclusión de una PEGA, desencadenado por los antibióticos recibidos, ceftriaxona o imipenem-cilastatina. Tras 6 días de la suspensión de imipenem-cilastatina, paciente mostró mejoría de lesiones dérmicas, con leve eritema y escasa descamación fina.
Acute generalized exanthematic pustulosis (PEGA) is a rare dermatological pathology characterized by the sudden and generalized appearance of multiple, sterile, non-follicular, punctate pustules on an erythematous and edematous base. It is frequently triggered by drugs, among which antibiotics stand out. We present the case of a 40-year-old male patient who was admitted to the emergency room due to abdominal pain síndrome, to rule out intra-abdominal tumor pathology, initially indicating ceftriaxone and metronidazole. The next day, he was re-admitted to the emergency room, finding, after emergency surgery, acute appendicitis complicated with intestinal perforation, for which they rotated the antibiotic therapy to imipenem-cilastatin + metronidazole. At the next 48 hours, he presents generalized erythema and some small pustules and microvesicles in the thoracic region, upper extremities and neck. Likewise, it is shown in laboratory tests, neutrophilic leukocytosis and hypoalbuminemia. In the biopsy, subcorneal and intraepidermal neutrophilic pustules are found, with edematous papillary dermis and perivascular inflammatory infiltrate with the presence of neutrophils and few eosinophils. With everything described above, we reached the conclusion of a PEGA, triggered by received antibiotics, ceftriaxone or imipenemcilastatin. After 6 days of the suspension of imipenem-cilastatin, the patient shows improvement of dermal lesions, with mild erythema and scant fine scaling.
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ABSTRACT The aim of this study was to discuss a case of late-onset Klebsiella oxytoca keratitis after deep anterior lamellar keratoplasty and its treatment. A 21-year-old female patient presented with redness and effluence in the left eye at 5 months after uncomplicated deep anterior lamellar keratoplasty surgery. In the examination, a single suture was loosened in the superior nasal region and there was an infiltration area and epithelial defect in the graft and recipient bed junction in the area of the loose suture. Topical fortified vancomycin and fortified ceftazidime treatment was started empirically hourly, but there was insufficient response. After K. Oxytoca growth in a swab and suture culture taken from the patient, fortified vancomycin was replaced with fortified imipenem. It was observed that the infiltration area rapidly regressed and the epithelial defect was closed after fortified imipenem treatment. Fortified imipenem may be considered as an alternative treatment, especially in cases in which there is no response to treatment and culture growth is detected.(AU)
RESUMO O objetivo deste estudo é discutir um caso de ceratite tardia por Klebsiella oxytoca, após ceratoplastia lamelar anterior profunda, bem como seu tratamento. Uma paciente de 21 anos apresentou vermelhidão e efluxo no olho esquerdo 5 meses após cirurgia de ceratoplastia lamelar anterior profunda sem complicações. Ao exame, havia uma única sutura solta na região nasal superior e uma área de infiltração com defeito epitelial no enxerto e na junção com o leito receptor na área da sutura solta. Iniciou-se empiricamente um tratamento tópico com vancomicina e ceftazidima fortificada de hora em hora, porém com resposta insuficiente. Após o crescimento de K. oxytoca a partir de cultura de swab e sutura retirados da paciente, a vancomicina fortificada foi substituída por imipenem fortificado. Observou-se que a área de infiltração regrediu rapidamente e que o defeito epitelial foi fechado com o tratamento com imipenem fortificado. O imipenem fortificado pode ser considerado um tratamento alternativo, especialmente nos casos sem resposta ao tratamento e detecção de crescimento na cultura.(AU)
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Humans , Male , Adult , Imipenem/therapeutic use , Corneal Transplantation , Klebsiella oxytoca/isolation & purification , Keratitis/diagnosisABSTRACT
Objective:To investigate the in vitro antibacterial effects of imipenem combined with common antibiotics on bla KPC-2 type carbapenem resistant klebsiella pneumoniae (CRKP) targeting bla KPC-2 gene. Methods:Six strains of unrepeated bla KPC-2 type confirmed by polymerase chain reaction and DNA sequence were isolated in Yueqing People's Hospital, China between January 2018 and January 2019 were included in this study. The susceptibility rate of imipenem against nine conventionally used antibiotics was determined. The sensitivity test of imipenem combined with eight antibiotics was performed with the checkerboard method. Fractional inhibitory concentration was calculated to assess the efficacy of imipenem combined with common antibiotics. The in vitro treatment time-antibacterial effect curve was drawn to evaluate the antibacterial effects. Results:The resistance rate of six strains of bla KPC-2 type was 100.00% (6/6) for imipenem, meropenem, ceftazidime, ciprofloxacin, rifampicin and cefotaxime, and it was 66.67% (4/6) for minocycline and clavulanic acid and 33.33% (2/6) for tigecycline. Imipenem combined with tigecycline had a better antibacterial effect and exhibited a synergistic effect on four strains of bla KPC-2 type CRKP and an additive effect on two strains of Bla KPC-2 type CRKP. The curve of time for in vitro treatment of KPN2 with imipenem combined with tigecycline against bactericidal effect revealed that the antibacterial rate of imipenem at the 1/2 minimum inhibitory concentration combined with tigecycline at the 1/4 minimum inhibitory concentration was > 95% at (t+2) and the antibacterial effect could maintain (t+10) hours to (t+12) hours. The antibacterial rate of imipenem combined with tigecycline against strain 002 was gradually decreased with time, and the growth curve of strain 002 rised gradually. Conclusion:In vitro drug sensitivity test revealed that imipenem combined with tigecycline exhibits a good synergistic effect on bla KPC-2 type CRKP. Findings from this study provide a reference for clinical treatment of bla KPC-2 type CRKP.
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Drug-resistant Acinetobacter baumannii is a frightening reality. The aim of this study is to examine the expression profiles of blaOXA-51 gene in carbapenemases producing A. baumannii treated with imipenem/sulbactam combination. Carbapenemases producing A. baumannii was identified among clinical isolates of A. baumannii obtained from patients at Shahid Rajaee hospital, Gachsaran, Iran, from January to June 2018. Synergism testing of imipenem/sulbactam on carbapenemases producing A. baumannii was carried out by broth microdilution method. Eventually, the expression of blaOXA-51 gene was carried out to investigate the inhibitory properties of imipenem/sulbactam combination against carbapenemases producing A. baumannii using quantitative real time RT-PCR. Among A. baumannii isolates, 24% were carbapenemases producing A. baumannii. Imipenem/sulbactam combination revealed synergistic and partial synergistic effect for all tested isolates (FIC= 0.313-0.75). Finally, imipenem/sulbactam combination displayed significant down-regulation of blaOXA-51 gene in carbapenemases producing A. baumannii. Imipenem synergizes with sulbactam against carbapenemases producing A. baumannii by targeting of the blaOXA-51 gene.
Subject(s)
Sulbactam/agonists , Imipenem/agonists , Acinetobacter baumannii/drug effects , Patients/classification , In Vitro Techniques/instrumentation , Pharmaceutical Preparations/analysis , Hospitals/classification , MethodsABSTRACT
AIM: To investigate the effects of imipenem-cilastatin sodium combined with immunoglobulin on serum PCT, hs-CRP and TNF-α in child with baby sepsis complicated with disseminated intravascular coagulation (DIC). METHODS: Ninty-two cases of patients with sepsis and DIC neonates admitted to our hospital from January 2013 to April 2019 were enrolled in this study. All the children were divided into observation group and control group according to random number table method, 46 cases in each group. The patients in the control group were treated with imipenem-cilastatin sodium, and the patients in the observation group were treated with imipenem-cilastatin sodium combined with immunoglobulin. The efficacy of the two groups, the time of DIC index returned to normal, bleeding stopped and ICU hospitalization time, coagulation parameters (FIB, PLT, D-D, TT), serum inflammatory factor levels and incidence of adverse reactions were compared. RESULTS: The total effective rate of treatment in the observation group was 93.48% (43/46), which was higher than that in the control group (78.26%, 36/46) (P0.05). CONCLUSION: Imipenem-cilastatin combined with immunoglobulin is effective in the treatment of baby sepsis complicated with DIC. It can alleviate or eliminate bleeding and other symptoms, shorten ICU hospitalization time, improve coagulation function, and reduce serum PCT and hs-CRP, TNF-α expression, and the body's inflammatory response, combined with fewer adverse reactions, which has a higher clinical value.
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OBJECTIVE: To compare and evaluate different methods of estimating %T>MIC based on drug concentration monitoring data, and clarify the implementation plan and treatment objectives of therapeutic drug monitoring. METHODS: The plasma drug concentrations of 25 patients with severe infections were collected at multiple time points after imipenem reached steady state. A population pharmacokinetic model was established by NONMEM method. The plasma drug concentrations were estimated by Bayesian feedback method at 6 and 8 h after imipenem administration. Meanwhile, the established calculation model of %T>MIC combined with the same drug concentrations was used to estimate the %T>MIC. The results of these two methods were compared with the true value of %T>MIC. RESULTS: The established population pharmacokinetic model could fit the data well. The covariate serum creatinine (CR) had a significant effect on the apparent distribution volume (Vc) of central ventricle. The final model was Vc=18.8×(CR/70.9)ΘCR_VC. When MIC=2, the results of Bayesian method and %T>MIC calculation model method showed 76.9% and 84.6% deviation within±10% of the true values, respectively. CONCLUSION: The two methods had good predictive accuracy when the MIC breakpoint was less than 2, but they decreased with the increase of MIC. Different therapeutic drug monitoring schemes should be considered for different levels of MIC.
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OBJECTIVE: To explore the application of therapy drug monitoring of imipenem in ICU, and to provide evidence for the use of imipenem in critically ill patients. METHODS: A cross-sectional survey was conducted to collect clinical data of 67 patients receiving therapeutic drug monitoring of imipenem in ICU from January 1, 2016 to December 31, 2018. Using SPSS21.0 statistical software, 71 cases of therapeutic drug monitoring data (blood drug concentration, f%T>MIC) and related clinical data were analyzed. RESULTS: Of all 71 cases of therapeutic drug monitoring, there are 37 cases (52.11%) f%TMIC≥40%,26 cases(36.62%)f%TMIC70%,and 10 cases(14.08%) f%TMIC=100%. f%TMIC of all cases with 0.25 g q6h were 70%. Among other dosage regimens, the highest proportion of f%T>MIC>40% was 1 g q12h (66.67%) and the highest proportion of f%T>MIC>70% was 0.5 g q8h(43.59%). According to different f%T>MIC, those patients were divided into ≤40% group, >40%-70% group and>70%group. Only group>70% showed a downward trend in the infection index of patients before and after medication. The body temperature decreased significantly (P=0.004), while the average PCT level of group MIC>70% group showed a downward trend in serum creatinine after treatment, but there was no significant difference (P=0.285). The serum drug concentration in CRRT group was slightly higher than that in non-CRRT group, and there was no significant difference in f%T>MIC (P=0.376, P=0.209, P=0.988). CONCLUSION: The level of f%T>MIC of imipenem in ICU is unsatisfactory. For critically ill patients, when imipenem f%T>MIC>70%, the antimicrobial effect is better.
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Background: The war against multidrug-resistant bacteria is challenging and of global concern. Hospitals are increasingly plagued by resistant gram negative pathogens. Bacteria of the family Enterobacteriaceae such as Escherichia coli and Klebsiella pneumoniae are part of the normal human intestinal flora but are also often responsible for community- and healthcare-associated infections. These bacteria are prone to acquiring resistance genes.Methods: Rectal swabs/swabs from the peri-anal area of the patients who were admitted in the Intensive Care Unit (ICU) of the accident and emergency department of this teaching hospital. Swabs were collected first on day 1 of admission, then day 4, and thereafter weekly during the period of stay in the ICU. All the swabs were immediately inoculated into trypticase soy broth with one 10μg meropenem disc and were incubated overnight at 35±2ºC, ambient air. Next day, the broth was vortexed, and then sub-cultured onto a MacConkey agar plate. On the third day, MacConkey agar plates were examined for lactose fermenting (pink-coloured) colonies. The representative isolated colonies were subjected to conventional antimicrobial susceptibility testing by the Kirby Bauer Disc diffusion method following the CLSI guidelines to know the susceptibility to carbapenem and other antimicrobial agents. Carbapenemase production was done by a Modified Hodge Test (MHT) and Imipenem-EDTA test.Results: Out of 89 patients, carbapenem resistant Klebsiella pneumoniae and E. coli isolates were recovered from 35 (39.3%) patients i.e. Klebsiella pneumoniae isolates from fifteen patients and carbapenem resistant E. coli isolates from twenty patients. Prevalence of carbapenemase producing isolates was found to be 1.42%. Conclusions: Surveillance for CRE can definitely help reduce rates of healthcare associated infections.