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Background: The outcome of heart transplantation is significantly affected by perioperative infections. Individualised immunosuppression strategies are essential to reduce the risk of such infections., Case Presentation: We report the successful management of a 56-year-old male patient diagnosed with dilated cardiomyopathy who underwent heart transplantation. During the perioperative period, the patient was prescribed cefoperazone sodium and sulbactam sodium, which induced a severe skin reaction: toxic epidermal necrolysis (TEN). The patient was treated with prednisone, immunoglobulins, etanercept, and other active immunomodulatory measures, together with an individualised anti-rejection regimen and physical therapy. The systemic rash resolved within a month, and the patient was successfully discharged after surgery., Conclusion: Effective management of heart transplantation necessitates balancing immunosuppression and infection prevention. Individualised immunosuppressive strategies are critical for optimal clinical outcomes., (© 2024. The Author(s).)

Objective: To evaluate associations between patient characteristics and cefoperazone/sulbactam-associated coagulation dysfunction., Methods: Retrospective analysis was performed on 821 cases of bacterial infection treated with cefoperazone/sulbactam for more than three days in the Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University, from January 2018 to June 2022. The patients were divided into normal coagulation function group (NCFG) (781 cases) and abnormal coagulation function group (ACFG) (40 cases) according to their coagulation function. Univariate and multivariate logistic regression analysis used the general data of the two groups of patients to investigate the risk factors of abnormal coagulation function caused by cefoperazone/sulbactam., Results: The incidence of abnormal coagulation function caused by cefoperazone/sulbactam was 4.87% (40/821). There was no significant difference in gender, body mass index (BMI), marriage, educational background, and concurrent medical conditions between the two groups (all P > .05). The patients in ACFG were older, the dosage and duration of cefoperazone/sulbactam were more prolonged, and the liver and kidney functions were more abnormal than those in NCFG, with significant differences (all P < .05). Univariate and multivariate logistic regression analysis showed that age (≥ 65 years old) (OR=1.293, 95%CI:0.897-1.287), duration of therapy (>10d) (OR=1.765, 95%CI:1.052-3.761), daily dosage (>6g) (OR=3.291, 95%CI:1.732-6.871), aspartate aminotransferase (AST) (≥ 23.98U/L) (OR=3.281, 95%CI:1.009-6.981), alanine aminotransferase (ALT) (≥ 24.03U/L) (OR=2.109, 95%CI:1.276-3.298), and serum creatinine (SCR) (>107 μ mol/L) (OR=2.716, 95%CI:1.023-4.398), prothrombin time (PT) (≥ 13.9U/L) (OR=1.571, 95%CI:1.287-1.945) were the risk factors (P < .05)., Conclusion: Elderly patients, time of use, daily dose of use, liver and kidney function, and PT are the risk factors of cefoperazone/sulbactam leading to abnormal coagulation function.

This study aim to assess the clinical efficacy and safety of generic cefoperazone/sulbactam compared to the branded cefoperazone/sulbactam (Sulperazon) in treating bacterial infections through a meta-analysis. Searches were conducted across PubMed, Embase, Cochrane Library, CNKI, WanFang, VIP databases, and Clinical Trials database, resulting in the inclusion of 11 studies comprising 7 randomized controlled trials (RCTs) and 4 retrospective cohort studies (RCSs). Meta-analysis of the RCTs indicated no statistical differences in clinical success rates, clinical cure rates, microbiological eradication rates, and incidence of adverse reactions between the generic cefoperazone/sulbactam and the branded version. Findings from the RCSs aligned with those from the RCTs, demonstrating that generic versions of cefoperazone/sulbactam are equivalent in efficacy and safety to their branded counterparts in treating bacterial infections.

Background and Aim: The use of cefoperazone/sulbactam (CPZ/SAM) could commonly cause vitamin K-dependent coagulation disorders and even hemorrhage sometimes. However, there is a lack of prediction tools estimating the risk for this. This study aimed at developing and internally validating a model for predicting CPZ/SAM-associated coagulation disorders in Chinese inpatients., Methods: A case-control study was conducted in 11,092 adult inpatients admitted to a Chinese general hospital between 2020 and 2021 and treated with CPZ/SAM. Patients with CPZ/SAM-associated coagulation disorders were identified through the Adverse Drug Events Active Surveillance and Assessment System-II and subsequent manual evaluation. Controls were selected from eligible patients who didn't develop coagulation disorders after CPZ/SAM therapy, with a 1:1 propensity score matching. The final predictors were obtained by univariable and multivariable logistic regression analyses. Internal validation and calibration for the model were performed using 1000 bootstrap resamplings., Results: 258 patients were identified as CPZ/SAM-associated coagulation disorders in 2184 patients eligible for inclusions and exclusions and the incidence was 11.8%. A final population of 252 cases and 252 controls was included for model development and validation. Malnutrition (OR = 2.41 (1.56-3.77)), history of recent bleeding (OR = 1.95 (1.32-2.90)), treatment duration (OR = 1.10 (1.07-1.14)), combination with carbapenems (OR = 4.43 (1.85-11.88)), and serum creatinine (OR = 1.01 (1.00-1.01)) were identified as final predictors. The model showed good discrimination, calibration, and clinical practicality, with the validated area under the receiver operating characteristic curve being 0.723 (0.683-0.770)., Conclusions: The model with good performance quantifies the risk for CPZ/SAM-associated coagulation disorders, and may support individual assessment and interventions to mitigate the risk after external validation., (© 2024. The Author(s).)

Cefoperazone (CPZ) is an antibiotic widely used for moderate to severe infections, especially in countries where resources are difficult to access. This case report aimed to draw attention to coagulopathy, a potential side effect of CPZ. This side effect can cause high mortality and morbidity in patients. In the mechanism of CPZ causing coagulopathy, it is reported that effects such as binding to vitamin K, disrupting vitamin K metabolism, and preventing platelet aggregation are responsible. In this presentation, a case who came to the emergency department with the complaint of hematuria caused by coagulopathy after the use of CPZ-containing antibiotics (CPZ + sulbactam) is presented., (Copyright © 2024 Emergency Nurses Association. Published by Elsevier Inc. All rights reserved.)

Purpose: To analyze the risk factors influencing the development of cefoperazone-induced coagulopathy in critically ill patients and determine the threshold of serum trough concentration., Methods: A retrospective case-control study was conducted in the intensive care unit patients treated with cefoperazone, and it was approved by the Ethical Committee of Drum Tower Hospital affiliated with the Medical School of Nanjing University (NO.2023-158-01). Patients were divided into the normal group and coagulopathy group based on prothrombin time. The clinical characteristics of the two groups were compared using univariate analysis. The serum concentration threshold and influencing factors of cefoperazone-induced coagulopathy in critically ill patients were analyzed using the receiver operating characteristic curve and multivariate logistic regression analysis., Results: A total of 113 patients were included, and cefoperazone-induced coagulopathy occurred in 39 patients, with an incidence of 34.5%. These patients experienced significant prothrombin time prolongation around day 6 (median) after cefoperazone application. The serum trough concentration threshold of cefoperazone-induced coagulopathy in critically ill patients was 87.765 mg/l. Multivariate logistic regression analysis revealed that the APACHE II score (p = 0.034), prophylactic use of vitamin K 1 (p < 0.001), hepatic impairment (p = 0.014), and C min  ≥ 87.765 mg/l (p = 0.005) were associated with cefoperazone-induced coagulopathy., Conclusion: Cefoperazone-induced coagulopathy usually occurs on the 6th day of cefoperazone use in critically ill patients. The risk will increase in patients with an APACHE II score > 25, hepatic impairment, and cefoperazone C min  ≥ 87.765 mg/l. Vitamin K 1 is effective in preventing this adverse reaction., (© 2024. The Author(s).)

Cefoperazone/sulbactam-induced hypoprothrombinaemia is associated with longer hospital stays and increased risk of death. The aim of this study was to develop and validate a nomogram for predicting the occurrence of cefoperazone/sulbactam-induced hypoprothrombinaemia in hospitalized adult patients. This retrospective cohort study involved hospitalized adult patients at Xi'an Central Hospital from January 2020 to December 2022 based on the Chinese pharmacovigilance system developed and established by the Adverse Drug Reaction Monitoring Center in China. Independent predictors of cefoperazone/sulbactam-induced hypoprothrombinaemia were obtained using multivariate logistic regression and were used to develop and establish the nomogram. According to the same standard, the clinical data of hospitalized patients using cefoperazone/sulbactam at the Third Affiliated Hospital of Xi'an Medical University from January 1, 2023 to June 30, 2023 were collected as the external validation group. The 893 hospitalized patients included 95 who were diagnosed with cefoperazone/sulbactam-induced hypoprothrombinaemia. Our study enrolled 610 patients: 427 in the training group and 183 in the internal validation group. The independent predictors of cefoperazone/sulbactam-induced hypoprothrombinaemia were surgery (odds ratio [OR] = 5.279, 95% confidence interval [CI] = 2.597-10.729), baseline platelet count ≤50×109/L (OR = 2.492, 95% CI = 1.110-5.593), baseline hepatic dysfunction (OR = 12.362, 95% CI = 3.277-46.635), cumulative defined daily doses (OR = 1.162, 95% CI = 1.162-1.221) and nutritional risk (OR = 16.973, 95% CI = 7.339-39.254). The areas under the curve (AUC) of the receiver operating characteristic for the training and internal validation groups were 0.909 (95% CI = 0.875-0.943) and 0.888 (95% CI = 0.832-0.944), respectively. The Hosmer-Lemeshow tests yielded p = 0.475 and p = 0.742 for the training and internal validation groups, respectively, confirming the goodness of fit of the nomogram model. In the external validation group (n = 221), the nomogram was equally robust in cefoperazone/sulbactam-induced hypoprothrombinaemia (AUC = 0.837, 95%CI = 0.736-0.938). The nomogram model constructed in this study had good predictive performance and extrapolation, which can help clinicians to identify patients at high risk of cefoperazone/sulbactam-induced hypoprothrombinaemia early. This will be useful in preventing the occurrence of cefoperazone/sulbactam-induced hypoprothrombinaemia and allowing timely intervention measures to be performed., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Bai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

BACKGROUND Owing to its broad-spectrum antibacterial activity, strong antibacterial effects, and ß-lactamase stability, cefoperazone/sulbactam has been recognized as a first-line empirical drug for treating severe infections. However, its administration is also characterized by numerous adverse effects, including coagulation dysfunction. Here, we summarize past clinical treatment data to provide data support for clinical use of cefoperazone sulbactam. MATERIAL AND METHODS We retrospectively analyzed the clinical medical records of 820 patients treated with cefoperazone/sulbactam from January 2015 to December 2020. A retrospective cohort study design was used. We assessed the general data of patients, age and sex distribution, type of primary disease, and incidence and days of abnormal blood coagulation with cefoperazone sulbactam. The chi-square test and t test were used to analyze the effect of cefoperazone sulbactam on coagulation function and the effect of vitamin K intervention on prognosis. RESULTS The rate of coagulation dysfunction was 24.39% (200 patients). Among these 200 patients, 50 were treated with vitamin K1. With increasing patient age, the number of patients with cefoperazone/sulbactam-induced coagulation dysfunction increased (peak at 81-90 years). APACHE II of coagulation dysfunction (15.54±4.095) was significantly higher than that in the normal group. It occurred at days 2-19 after administration of 9.0 g/day of cefoperazone/sulbactam. Measured coagulation indices were significantly higher after treatment with cefoperazone/sulbactam than before treatment, including international normalized ratio, prothrombin time, and activated partial thrombin time (P<0.0001). CONCLUSIONS All coagulation indices decreased significantly after vitamin K1 intervention, indicating improved coagulation function, especially in patients with high APACHE II scores. Hence, regulated vitamin K1 administration can benefit patients with coagulation dysfunction in clinical treatment.

Beta-lactam antibiotics commonly cause immune thrombocytopenia. Cross-reactivity in patients with drug-induced immune thrombocytopenia has rarely been reported. In this study, we describe the case of a 79-year-old man who developed thrombocytopenia after receiving piperacillin-tazobactam for an acute exacerbation of chronic obstructive pulmonary disease, and he was successfully treated with meropenem and cefotiam. However, thrombocytopenia recurred after cefoperazone-sulbactam administration. This indicated that cross-reactivity of platelet-specific antibodies occurred between piperacillin-tazobactam and cefoperazone-sulbactam. However, the responsible drug structures remain unknown, requiring further investigation. Likewise, chemical structure similarities among beta-lactam antibiotics must be examined to determine the risk of immune thrombocytopenia in the clinical setting.

Introduction: The aims of the study were to investigate the risk factors of tigecycline-induced hypofibrinogenemia and to evaluate the safety of tigecycline with concomitant antithrombotic drugs., Methods: We performed a retrospective analysis of patients who received tigecycline for more than 3 days between January 2015 and June 2019. Clinical and laboratory data were collected including fibrinogen concertation, tigecycline dose, duration of treatment, disease severity, complete blood count, indicators of infection, liver and renal function. Risk factors of hypofibrinogenemia were analyzed by univariate and multivariate analysis. To evaluate the safety of tigecycline and concomitant antithrombotic drugs, bleeding events were assessed by comparing the decline in hemoglobin and the amount of red blood cell transfusion in patients with antithrombotic drugs and those without., Results: This study included a total of 68 cases, 20 of which experienced hypofibrinogenemia while receiving tigecycline treatment. Duration of treatment, cefoperazone/sulbactam combination therapy, and fibrinogen levels prior to initiation of tigecycline were risk factors associated with tigecycline-induced hypofibrinogenemia. There were 26 recorded bleeding incidents, 25 of which happened before the start of tigecycline. Antithrombotic and non-antithrombotic patients did not differ in their hemoglobin decline or need for red blood cell transfusions while taking tigecycline., Conclusion: A longer treatment duration, cefoperazone/sulbactam combination therapy, and a lower level of fibrinogen before tigecycline were associated with an increased risk of tigecycline-induced hypofibrinogenemia. A combination of antithrombotic drugs and tigecycline did not aggravate the bleeding events during tigecycline treatment., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Drug-induced hemolytic anemia (DIHA) is a rare complication of drug therapy and usually underdiagnosed. Cefoperazone/sulbactam is a compound prepared from the third generation of cephalosporin and β-lactamase inhibitor. There are limited data of DIHA induced from cefoperazone/sulbactam. A 93-year-old female patient, who had an operation on the biliary tract 3 months ago, was admitted to our hospital with an abdominal infection. After cefoperazone/sulbactam was given as anti-infection treatment, the patient developed hemolytic anemia on the third day. Cefoperazone/sulbactam was discontinued and replaced with meropenem. Subsequently the level of red blood cells, hemoglobin, and hematocrit returned to normal. Clinicians should pay attention to monitoring the possible adverse reactions during the use of cefoperazone/sulbactam and should be aware of the occurrence of DIHA, so as to give timely treatment., Competing Interests: None

Background: Intracranial infection is a serious complication after neurosurgery. According to a survey, the incidence of intracranial infection is about 2.2%-2.6%, and patients with severe symptoms may even pose a threat to their life safety., Objective: To explore the risk factors for intracranial infection caused by Acinetobacter baumannii after surgery and the clinical effect of sequential therapy of cefoperazone/sulbactam sodium., Methods: In this study, a retrospective study was used. In this case-control study, 48 cases of intracranial Acinetobacter baumannii infection after neurosurgery in our hospital from January 2016 to December 2021 were selected as the infection group, and 96 patients without intracranial infection after surgery during the same period were selected as the control group to study all kinds of related factors and analyze the risk factors for intracranial Acinetobacter baumannii infection; in addition, in accordance with the therapeutic regimen for anti-infection, the infection group was divided into the tigecycline group (patients with tigecycline therapy in this group) and the combined group (patients with tigecycline combined with cefoperazone/sulbactam sequential therapy), with 24 cases in each group in order to compare the therapeutic effects of the two groups., Results: Logistic regression factor model results show that increasing age of patients, surgical treatment for intracranial tumor or craniocerebral trauma, postoperative drainage time (≥3 days), and postoperative hospital stay (≥10 days) were the risk factors for postoperative intracranial infection of Acinetobacter baumannii in neurosurgical patients ( P < 0.05), and postoperative prophylactic antibiotic treatment can reduce the incidence of intracranial infection ( P < 0.05). The cerebrospinal fluid nucleated cell count, serum CRP, and serum PCT in the combined group 72 h after treatment were lower than those in the tigecycline group, and the difference was statistically significant ( P < 0.05). Compared with the clinical efficacy after 72-hour treatment, the cure rate and effective rate in the combined treatment group were 83.33% and 16.67%, respectively, and those in the tigecycline group were 54.17% and 33.33%, respectively. The invalid interest rate was 12.50%, and the combined treatment group was superior to the tigecycline group ( P < 0.05)., Conclusion: For patients with craniocerebral surgery, targeted preventive interventions should be carried out for the risk factors that may lead to intracranial Acinetobacter baumannii infection. The clinical effect of tigecycline combined with cefoperazone and sulbactam sodium sequentially in the treatment of intracranial Acinetobacter baumannii infection is better., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Zezhong Xiong et al.)

Antibiotic abuse can lead to gut microbiota disturbance and intestinal inflammation, which in turn may lead to serious inflammatory bowel disease and metabolic syndromes. To investigate the effect of fucoidan on alleviation of the side effects of antibiotics and its structure-activity relationship, we compared the effects of two fucoidan fractions with medium and low molecular weights (MF and LF) from Laminaria japonica on microbiota dysbiosis, colonic inflammation and intestinal mucosal damage in a cefoperazone-induced intestinal injury mouse model. Our results showed that oral administration of 200 mg kg -1 LF ( M w = 1.13 kDa) and MF ( M w = 26.7 kDa) together with 100 mg kg -1 cefoperazone for 10 days could significantly alleviate weight loss, colon shortening and enlargement, mucosal structural damage in the small intestine, cecum and colon induced by cefoperazone in mice. Meanwhile, LF and MF also significantly suppressed the overproduction of TNF-α, IFN-γ, and IL-6 in the colon; however, LF can restore the decrease in the levels of TNF-α and IL-6 in the small intestine and the decrease in the levels of TNF-α, IFN-γ, and IL-6 in the cecum induced by cefoperazone in mice. We found that the molecular weight of fucoidan plays an important role in the regulation of the gut microbiota in antibiotic-treated mice. Interestingly, fucoidans with different molecular weights resulted in quite different caecal microbiota communities. MF exhibited a much better effect on the restoration of the gut microbiota community richness and diversity and the beneficial bacterium Muribaculaceae . However, LF resulted in the dominance of bacteria including Staphylococcus in cefoperazone treated mice, without an increase in the community richness and diversity of caecal microbiota. In the LF and MF treated mice, an increase in the abundance of beneficial bacteria, Muribaculaceae , Acinetobacter&#95;lwoffii and Alloprevotella , and a decrease in the abundance of harmful bacteria, e.g. , Parasutterella , Helicobacter and Enterococcus were also observed. Considering the negative effect of LF on the gut microbiota, MF with a molecular weight of 26.7 kDa seemed to be a more suitable choice of prebiotics for patients receiving cefoperazone treatment.

Background: In this systematic review and meta-analysis, we aimed to assess the clinical efficacy and safety of cefoperazone-sulbactam against alternative antibiotics in the treatment of intra-abdominal infections. Methods: The PubMed, Cochrane, Web of Science, Ovid Medline, and CKNI databases were searched for relevant articles up to November 25, 2020. The primary outcome was clinical efficacy rate, and the secondary outcomes were microbiologic eradication rate, mortality rate, and adverse event (AE) risk. Results: Twelve studies involving 1,674 patients were included. Overall, the clinical efficacy rate of cefoperazone-sulbactam and comparators was 87.7% and 81.7%, respectively, and cefoperazone-sulbactam was associated with a higher clinical efficacy rate than that the comparator (odds ratio [OR] 1.98; 95% confidence interval [CI] 1.31-3.00; I 2  = 36%). Additionally, cefoperazone-sulbactam was associated with a lower clinical failure rate (OR 0.40; 95% CI 0.28-0.57; I 2  = 0) and a higher clinical cure rate (OR 1.54; 95% CI 1.17-2.03; I 2  = 0) than the comparators. Cefoperazone-sulbactam was associated with a higher microbiologic eradication rate than the comparator (OR 2.54; 95% CI 1.72-3.76; I 2  = 0). Finally, there was no significant difference between cefoperazone-sulbactam and the comparators in terms of mortality rate (OR 090; 95% CI 0.38-2.16; I 2  = 0) and AE risk (OR 1.07; 95% CI 0.74-1.55; I 2  = 0). Conclusions: The clinical efficacy and safety of cefoperazone-sulbactam were similar to those of alternative antibiotics in the treatment of intra-abdominal infections. Therefore, cefoperazone-sulbactam could be recommended as an effective and safe antibiotic for treating intra-abdominal infections.

Objective: To compare the occurrence and prognosis of antibiotic-associated diarrhea (AAD) between patients treated with cefoperazone/sulbactam and piperacillin/tazobactam in the neurosurgery department., Methods: This study retrospectively analyzed patients who received cefoperazone/sulbactam or piperacillin/tazobactam to prevent or treat hospital-acquired infections in the Department of Neurosurgery of The First Medical Center of Chinese PLA General Hospital between October 2019 and October 2020. For patients with AAD, clinical data, antibiotic usage, the incidence of diarrhea, treatment, and prognosis were collected and analyzed., Results: In total, 356 patients were enrolled, and 65 (18.6%) experienced AAD, 38 patients in the cefoperazone/sulbactam group and 27 patients in the piperacillin/tazobactam group. The AAD rate did not differ between the treatment arms. Conversely, the dosage, intensity, and duration of antibiotic therapy differed between the groups, whereas no differences were noted in the time to the appearance of diarrhea and prognosis. According to regression analysis, the incidence of AAD did not differ between the groups (odds ratio [OR] = 0.85, 95% confidence interval [CI] = 0.46-1.48)., Conclusion: Cefoperazone/sulbactam or piperacillin/tazobactam can lead to a similar incidence rate of AAD. The combined application of antibiotics and empiric therapy often occurs. The rational use of antibiotics should be improved.

We report a case of rashes in a patient undergoing cesarean section. She was administered cefoperazone and sulbactam sodium + metronidazole sodium chloride combined with morphine hydrochloride perioperatively, which caused a rash as an adverse side effect. The patient, 35 years old, underwent lower uterine segment cesarean section under combined spinal-epidural anesthesia. She received intravenous infusion of cefoperazone sodium and sulbactam sodium + metronidazole sodium chloride for anti-infection therapy before operation and morphine hydrochloride for analgesia at the end of the operation. The patient later experienced skin itching and had rashes on the waist, abdomen, and back. According to the patient's physical signs, the correlation with drug injection time, and the adverse side effects reported in the drug instructions and related literature, the adverse side effect may have been caused by cefoperazone sodium and sulbactam sodium, metronidazole sodium chloride, and morphine hydrochloride. The drugs were suspended, and the patient was given anti-allergic treatment. After that, the above symptoms subsided. Therefore, we suspect that cefoperazone sodium and sulbactam sodium, metronidazole sodium chloride, or morphine hydrochloride injection, or a combination of two or more of these drugs, caused the adverse side effect of skin rash in the patient. This study reports a case of adverse side effects of skin itching and rash after the use of cefoperazone sodium and sulbactam sodium, metronidazole sodium chloride, and morphine hydrochloride in a pregnant woman undergoing cesarean section. The occurrence of adverse side effects in special populations should attract clinicians' attention. When giving such drugs, medical personnel should take a full history the patient's allergy and closely monitor the occurrence of adverse side effects in the early stages of medication.

Cefoperazone-sulbactam (CS) and piperacillin-tazobactam (TZP) are used in the treatment of Gram-negative nosocomial infections (NIs). We aimed to compare the effects of these two antibiotics on mortality and treatment success. Patients treated with CS or TZP empirically for at least three days with suspicion of NI were included in this retrospective study. In total, 308 (154 patients in both treatment arms) patients were analyzed. Treatment success rate in CS and TZP group respectively (50% vs 51.2%, p  = 0.18), 28-day mortality rate (46.1% vs 42.8%, p  = 0.56) and antibiotic-related side effects (50.6% vs 46.1%, p  = 0.42) were similar except prolonged prothrombin time (19.4% vs 6.4%; p  = 0.001). According to this study results, CS and TZP have equal effectivity and safety for the empirical treatment of Gram-negative NIs. CS may be an appropriate alternative to TZP for antibiotic cycling or mixing strategy to reduce antibiotic resistance.

Objectives : Limited evidence has suggested that cefoperazone-sulbactam causes coagulation disorders and bleeding. Methods : The authors conducted a retrospective study to compare patients receiving cefoperazone-sulbactam versus those treated with cefoperazone-tazobactam or ceftazidime. Propensity-score matching was used to explore whether treatment with cefoperazone-sulbactam increased the risk of prothrombin time (PT) prolongation, coagulation disorders, and bleeding, or decreased platelets (PLT). Results : The cohort included 23,242 patients. Among patients receiving cefoperazone-sulbactam, the risk of PT prolongation, coagulation disorders, decreased PLT, and bleeding was 5.3%, 9.2%, 15.7%, and 4.2%, respectively. Propensity-score matching analyses suggested that cefoperazone-sulbactam increased the risk of PT prolongation (aOR 2.26, 95% CI 1.61-3.18), coagulation disorders (aOR 1.81, 95% CI 1.43-2.30), and decreased PLT (aOR 1.46, 95% CI 1.25-1.72), but not increase bleeding (aOR 1.05, 95% CI 0.79-1.40) compared with ceftazidime. Patients receiving cefoperazone-sulbactam had higher risk of PT prolongation (aOR 1.53, 95% CI 1.11-2.10), coagulation disorders (aOR 1.53, 95% CI 1.21-1.95), but not decreased PLT (aOR 0.93, 95% CI 0.81-1.07) or bleeding (aOR 1.11, 95% CI 0.87-1.42), compared with those receiving cefoperazone-tazobactam. Conclusion : Cefoperazone-sulbactam may be associated with a higher risk of PT prolongation and coagulation disorders compared with cefoperazone-tazobactam and ceftazidime.

Clostridium difficile (Cd) infection (CDI) typically occurs after antibiotic usage perturbs the gut microbiota. Mucosa-associated invariant T cells (MAIT) are found in the gut and their development is dependent on Major histocompatibility complex-related protein 1 (MR1) and the host microbiome. Here we were interested in determining whether the absence of MR1 impacts resistance to CDI. To this end, wild-type (WT) and MR1-/- mice were treated with antibiotics and then infected with Cd spores. Surprisingly, MR1-/- mice exhibited resistance to Cd colonization. 16S rRNA gene sequencing of feces revealed inherent differences in microbial composition. This colonization resistance was transferred from MR1-/- to WT mice via fecal microbiota transplantation, suggesting that MR1-dependent factors influence the microbiota, leading to CDI susceptibility., Competing Interests: The authors have declared that no competing interests exist.

Cefoperazone, a third-generation cephamycin with broad-spectrum antibacterial activity and the ability to permeate bacterial cell membranes, is active against commonly encountered multidrug-resistant pathogens for hospital-acquired pneumonia (HAP) and health care-associated pneumonia (HCAP). To clarify the clinical effects of cefoperazone-sulbactam in the treatment of HAP and HCAP, we conducted an open-label, randomized, noninferiority trial that recruited patients aged ≥18 years suffering HAP/HCAP. Participants were randomly assigned to the cefoperazone-sulbactam (2 g of each per 12 h) or cefepime (2 g per 12 h) arm. Clinical and microbiological responses were evaluated at early posttherapy and test-of-cure visits. Recruited patients were allocated to subpopulations for intent-to-treat ( n  = 154), per-protocol ( n  = 147), and safety ( n  = 166) analyses. Intent-to-treat analysis demonstrated that (i) at the early posttherapy visit, 87.3% of patients receiving cefoperazone-sulbactam and 84.3% of patients receiving cefepime achieved clinical improvement or cure (risk difference of 3.0%; 95% confidence interval [CI], -9.0% to 15.0%), and (ii) at the test-of-cure visit, 73.1% of patients receiving cefoperazone-sulbactam and 56.8% of patients receiving cefepime were assessed as cured (risk difference of 16.3%; 95% CI, 0.0% to 33.0%). These results indicated the noninferiority of cefoperazone-sulbactam to cefepime, which was confirmed by per-protocol analysis. The chest radiographic consolidation/infiltration resolution rate, microbiological eradiation rate, and percentage of adverse events were comparable in both groups. Serious adverse events were rare, and none was judged to be related to the study drugs. Cefoperazone-sulbactam at 2 g every 12 h was noninferior to cefepime at 2 g every 2 h for patients with HCAP., (Copyright © 2019 American Society for Microbiology.)

Candida albicans is the fourth most common cause of systemic nosocomial infections, posing a significant risk in immunocompromised individuals. As the majority of systemic C. albicans infections stem from endogenous gastrointestinal (GI) colonization, understanding the mechanisms associated with GI colonization is essential in the development of novel methods to prevent C. albicans-related mortality. In this study, we investigated the role of microbial-derived short-chain fatty acids (SCFAs) including acetate, butyrate, and propionate on growth, morphogenesis, and GI colonization of C. albicans. Our results indicate that cefoperazone-treated mice susceptible to C. albicans infection had significantly decreased levels of SCFAs in the cecal contents that correlate with a higher fungal load in the feces. Further, using in vivo concentration of SCFAs, we demonstrated that SCFAs inhibit the growth, germ tube, hyphae and biofilm development of C. albicans in vitro. Collectively, results from this study suggest that antibiotic-induced decreases in the levels of SCFAs in the cecum enhances the growth and GI colonization of C. albicans.

Purpose: Beta lactams are standard empirical therapy for febrile neutropenia (FN). The aim of this study was to evaluate the efficacy and safety of cefepime monotherapy compared with cefoperazone/sulbactam plus amikacin (CS + A) for empirical treatment of high risk FN., Methods: One hundred seventy-five patients with 336 FN episodes were randomized to receive either cefepime (2 g q8h for adults and 50 mg/kg q8h for children) or CS (2 g q8h for adults and 50 mg/kg q8h for children) plus amikacin (15 mg/kg once a day). Positive response was defined as afebrile within 72 h of starting antibiotics, persistent afebrile status more than 48 h and no requirement of second-line antibiotics and antifungal agents., Results: Three hundred thirty-six episodes were assessable for efficacy (168 cefepime, 168 CS + A). The positive response to antibiotics was identical for cefepime (53%) and CS + A (53%). Positive response was similar in MDI (microbiologically documented infection), 50 vs. 35% (p = 0.248), CDI (clinically documented infection), 50 vs. 35% (p = 0.259), combination CDI + MDI, 25 vs. 15% (p = 0.400), FUO (fever of unknown origin), 68 vs. 72% (p = 0.577) respectively in the two groups. The successful discontinuation of antibiotics at 72 h in FUO was similar in both groups (60 vs. 59%, p = 0.544). Total drug-related adverse events were similar in both groups (8 vs. 6%) except renal dysfunction was high in CS + A (1 vs. 7 events). Mortality was the same between two groups (8 vs 7%)., Conclusions: Cefepime monotherapy and CS + A had similar efficacy as first-line therapy for FN. Discontinuation of empirical antibiotics is safe and feasible approach in selected group of FUO patients.

Candida albicans is a fungal pathogen that poses a significant public health risk due to high incidence and mortality rates among immunocompromised patients. Candida albicans infections begin with successful gastrointestinal (GI) colonization; however, the mechanisms behind this colonization remain to be elucidated. In this study, we investigated the role of taurocholic acid (TCA) on growth and GI colonization of C. albicans. Our results indicate that cefoperazone-treated mice susceptible to C. albicans infection had significantly increased levels of TCA in the gut contents. In addition, an increase in TCA levels directly correlates with higher C. albicans load in the fecal and gut contents of antibiotic-treated infected mice. Using in vitro assays, we also demonstrated that TCA enhances the growth of C. albicans and its ability to develop filamentous hyphae. Furthermore, TCA significantly increased the ability of C. albicans to attach to mammalian cells. These results demonstrate that antibiotic treatment alters TCA levels in the gut and potentially enhances GI colonization of C. albicans.

Objective: Empirical antibiotic therapy in neutropenic patients presenting with fever plays a significant role in reducing mortality related to infection. Empirical therapies with broad-spectrum intravenous bactericidal, anti-pseudomonal antibiotics are accepted treatments for febrile neutropenic patients. The aim of this study was to compare the efficacy of piperacillin-tazobactam (PIP-TAZO) and cefoperozone-sulbactam (CS) therapies in adult patients with haematological malignancies presenting with neutropenic fever in a prospective study design., Methods: Patients with haematological malignancies (leukaemia, lymphoma, multiple myeloma, and myelodysplastic syndrome) were recruited from June 2010-May 2013. Participants were over 18 years old, with an absolute neutrophil count (ANC) of less than 500/mm³ following chemotherapy or expected to have an ANC less than 500/mm³ in the first 48 h post-chemotherapy, and with an oral body temperature ≥ 38.3°C at a single measurement or 38.0°C after 1-h monitoring. Patients were randomised to the two treatment groups. The initial empirical therapy comprised PIP-TAZO (4.5 g/6 h/day, IV) and CS (2 g/8 h/day, IV)., Results: The overall success rate was 61% with CS and 49% with PIP-TAZO (p =0.247). Factors affecting the treatment success included a neutrophil count <100/mm3, being in the relapse/refractory stage of malignancy, and the presence of a microbiologically documented infection (p <0.05)., Conclusions: PIP-TAZO and CS monotherapies are equally effective and safe for the empirical treatment of febrile neutropenic patients.

The present study is a non-inferiority study based on a descriptive and comparative case series for comparison of generic vs. original intravenous antimicrobials in septic oncology patients at an oncology private ICU. 1906 cancer patients admitted to Arturo Lopez Perez Foundation, Chile, were included in this study. After recruitment, a first retrospective group of 206 septic cancer patients recorded from 1st January, 2008 until July 14th, 2010, treated with original antibiotics (cefoperazone-sulbactam, imipenem-cilastatin, piperacillin-tazobactam) were included for analyses and a second prospective group of 143 septic cancer patients recorded from July 15th, 2010 until January 02, 2013, treated with the same but generic antibiotics were also included for comparisons. The trial protocol was developed in accordance with Helsinki and Good Clinical Practices recommendations. The results of this study showed no significant differences between the 2 groups in days of treatment, rate of success and lab test determinations (white cell count, PCR and procalcitonin), with lower, but not significant, total bed days and CPU bed days for generic antibiotics. Therefore, we conclude that the safety and efficacy of the generic antibiotics cefactam®, imipen® and Piperazam® are not inferior to original antibiotics for the treatment of severe sepsis in hospitalised patients at the Arturo Lopez Perez Foundation., (© Georg Thieme Verlag KG Stuttgart · New York.)

Although imbalances in gut microbiota composition, or "dysbiosis," are associated with many diseases, the effects of gut dysbiosis on host systemic physiology are less well characterized. We report that gut dysbiosis induced by antibiotic (Abx) treatment promotes allergic airway inflammation by shifting macrophage polarization in the lung toward the alternatively activated M2 phenotype. Adoptive transfer of alveolar macrophages derived from Abx-treated mice was sufficient to increase allergic airway inflammation. Abx treatment resulted in the overgrowth of a commensal fungal Candida species in the gut and increased plasma concentrations of prostaglandin E₂ (PGE₂), which induced M2 macrophage polarization in the lung. Suppression of PGE₂ synthesis by the cyclooxygenase inhibitors aspirin and celecoxib suppressed M2 macrophage polarization and decreased allergic airway inflammatory cell infiltration in Abx-treated mice. Thus, Abx treatment can cause overgrowth of particular fungal species in the gut and promote M2 macrophage activation at distant sites to influence systemic responses including allergic inflammation., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: This clinical study was designed to evaluate the efficacy and safety of this therapy in the treatment of respiratory and urinary infections caused by ceftriaxone-resistant bacteria in comparison with the effect of cefoperazone/sulbactam on cefoperazone-resistant bacteria., Methods: A total of 285 patients aged from 18 to 65 years old, with a respiratory or urinary tract bacterial infection, were enrolled into this multicentre, open-label, controlled clinical study, and bacteria that were either ceftriaxone-resistant or cefoperazone-resistant were isolated from the patients, whose condition had not improved after three days of treatment with ceftriaxone or cefoperazone. To be selected for the study, bacterial cultures obtained from the patients had to be positive before enrolment, and all of the isolates were required to be β-lactamase-positive. Of these patients, 253 completed the trial, and 263 were enrolled into the intention-to-treat (ITT) analysis. All of the 285 patients were included in the safety analysis., Results: The cure and effective rates were 39.55% and 85.07% in the ceftriaxone/sulbactam group and 36.43% and 79.84% in the cefoperazone/sulbactam group; the bacterial eradication rates were 83.58% and 83.72%; and the adverse-event rates were 7.48% and 7.80%, respectively. There were no significant differences between the two groups (p > 0.05)., Conclusion: Ceftriaxone/sulbactam is as effective and well-tolerated as cefoperazone/sulbactam for the treatment of intermediate and severe bacterial infections caused by resistant strains.

Background: Monotherapy has tended to replace the combination therapy in emprical treatment of febrile neutropenia. There is no reported trial which compares the efficacy of cefoperazone-sulbactam (CS) and piperacillin-tazobactam (PIP/TAZO) monotherapies in the treatment of febrile neutropenia. In this prospective randomized study, we aimed to compare the safety and efficacy of CS versus PIP/TAZO as empirical monotherapies in febrile neutropenic children with cancer., Procedure: The study included febrile, neutropenic children hospitalized at our center for cancer. They were randomly selected to receive CS 100 mg/kg/day or PIP/TAZO 360 mg/kg/day. Duration of fever and neutropenia, absolute neutrophil count, modification, and success rate were compared between the two groups. Resolution of fever without antibiotic change was defined as success and resolution of fever with antibiotic change or death of a patient was defined as failure. Modification was defined as changing the empirical antimicrobial agent during a febrile episode., Results: One hundred and two febrile neutropenic episodes were documented in 55 patients with a median age of 4 years. In 50 episodes CS and in 52 episodes PIP/TAZO was used. Duration of fever and neutropenia, neutrophil count, age, sex, and primary disease were not different between two groups. Success rates in the CS and PIP/TAZO groups were respectively 56 and 62% (P > 0.05). Modification rate between two groups showed no significant difference (P > 0.05). No serious adverse effect occurred in either of the groups., Conclusion: CS and PIP/TAZO monotherapy are both safe and effective in the initial treatment of febrile neutropenia in children with cancer., (Copyright © 2011 Wiley Periodicals, Inc.)

Background: Regulatory T cells (Treg cells), which are essential for regulation of immune response to respiratory syncytial virus (RSV) infection, are promoted by pharyngeal commensal pneumococcus. The effects of pharyngeal microflora disruption by antibiotics on airway responsiveness and relative immune responses after RSV infection have not been clarified., Methods: Female BALB/c mice (aged 3 weeks) were infected with RSV and then treated with either oral antibiotics or oral double distilled water (ddH(2)O) from 1 d post infection (pi). Changes in pharyngeal microflora were analyzed after antibiotic treatment for 7 d and 14 d. At 8 d pi and 15 d pi, the inflammatory cells in bronchoalveolar lavage fluid (BALF) were investigated in combination with tests of pulmonary histopathology, airway hyperresponsiveness (AHR), pulmonary and splenic Treg cells responses. Pulmonary Foxp3 mRNA expression, IL-10 and TGF-β1 in BALF and lung homogenate were investigated at 15 d pi. Ovalbumin (OVA) challenge was used to induce AHR after RSV infection., Results: The predominant pharyngeal commensal, Streptococcus, was cleared by antibiotic treatment for 7 d. Same change also existed after antibiotic treatment for 14 d. After RSV infection, AHR was promoted by antibiotic treatment at 15 d pi. Synchronous decreases of pulmonary Treg cells, Foxp3 mRNA and TGF-β1 were detected. Similar results were observed under OVA challenge., Conclusions: After RSV infection, antibiotic treatment cleared pharyngeal commensal bacteria such as Streptococcus, which consequently, might induce AHR and decrease pulmonary Treg cells.

In patients with an impaired state of consciousness, EEG is fundamental, a correct neurological work-up. Cephalosporins have been identified as a case of triphasic waves' (TW) reversible encephalopathy. We report a case of an acute reversible encephalopathy with TWs during treatment with cefoperazone. We report the occurrence and regression of a confusional state with TWs encephalopathy at EEG after the administration of cefoperazone for urinary tract infection in a patient admitted for syncope. In conclusion, cefoperazone should be considered as a cause of toxic encephalopathy with EEG TWs, when there is a temporal relationship with its administration; EEG monitoring is useful in the neurological follow-up.

Simultaneous drug-induced immune hemolytic anemia (DIIHA) caused by multiple drugs is rare. We report a case of a patient who developed DIIHA caused by 2 drugs. The patient's serum exhibited agglutination of ceftizoxime- or sulbactam-coated red blood cells (RBCs; via a drug-adsorption mechanism) and of uncoated RBCs in the presence of sulbactam (via an immune-complex mechanism). Although ceftizoxime is known to exhibit a positive reaction by an immune-complex method with or without reactivity with drug-coated RBCs, this patient's antibodies were reactive only against drug-coated RBCs. On the other hand, sulbactam, which is known to cause hemolytic anemia by nonimmunologic protein adsorption, exhibited positive reactions in tests with both drug-coated RBCs and in the presence of sulbactam. This is the first report of DIIHA due to a sulbactam-cefoperazone combination and the fourth report of DIIHA due to ceftizoxime. Owing to the patient's complicated laboratory results, DIIHA was suspected only at a late stage. We propose that for the prompt diagnosis of DIIHA, tests for all possible causative drugs should be conducted by 2 methods.

Cefoperazone is a parenteral third generation cephalosporin which is active against many Gram positive and Gram negative organisms. Cefaperazone, like other cephalosporins which contain methyltiotetrazole side chain, can cause hypoprotrombinaemia and bleeding problems. Here we report a nine-year old child with Meckel's diverticulum who had cefoperazone induced massive gastrointestinal bleeding on the fifth day following the operation.

Background: Combinations of a third-generation cephalosporin and metronidazole, with or without an aminoglycoside, often are used for the treatment of intra-abdominal infections in surgical settings. Simpler regimens that preserve an adequate spectrum of coverage, but allow easier administration and have fewer side effects, may be a more desirable option., Methods: This randomized, open-label, active comparator study evaluated the effectiveness (non-inferiority hypothesis) of the beta-lactam/beta-lactamase inhibitor combination cefoperazone-sulbactam (2-8 g/day), compared with ceftazidime (2-6 g/day)-amikacin (15 mg/kg/day)-metronidazole (500 mg three times daily) in 154 and 152 subjects, respectively, having intra-abdominal infections. The study was conducted at 17 centers in India., Results: Non-inferiority of cefoperazone-sulbactam (91.9%) compared with ceftazidime-amikacin-metronidazole (81.8%) was demonstrated for continued resolution of clinical signs and symptoms at the 30-day follow-up (primary endpoint) with a treatment difference of 10.1% (95% confidence interval 2.1%, 18.1%; pre-defined non-inferiority limit > -12.5%). Superiority of cefoperazone-sulbactam also was demonstrated for this endpoint, with significantly more subjects achieving continued resolution at the 30-day follow-up than in the comparator group (p = 0.015). On microbiologic outcomes, cefoperazone-sulbactam had higher success rates than ceftazidime-amikacin-metronidazole (92.9% vs. 80.0%). The pathogens (202 isolated) isolated most commonly were Escherichia coli (38.6%) and Klebsiella spp. (12.9%). The incidence of treatment-related adverse events was 6.5% and 16.4% in the cefoperazone-sulbactam and ceftazidime-amikacin-metronidazole groups, respectively, with more discontinuations due to treatment-related adverse events in the comparator arm (3.2% vs. 9.9%)., Conclusion: Empirical cefoperazone-sulbactam monotherapy could be a useful adjunct to surgical intervention for intra-abdominal infections.

Cefoperazone and sulbactam are prescribed in combination and used in the treatment of moderate to severe bacterial infections. Serious anaphylaxis is a rare side effect. This report describes a fatal case of suspected anaphylaxis after intravenous administration of a combination of the two drugs. Heart blood was analyzed for cefoperazone by protein precipitation with acetonitrile and by liquid-liquid precipitation for sulbactam after protein precipitation with aqueous acetonitrile, followed by tandem mass spectrometry in the product ion scan mode for identification and by liquid chromatography mass spectrometry in the selected ion monitoring mode for quantitation. Calibration curves for cefoperazone and sulbactam were linear over the range 0.07 to 1.93 and 0.046 to 0.914 microg/ml respectively. The decedent's blood concentrations of cefoperazone and sulbactam were 0.368 and 0.143 microg/ml respectively. As these concentrations were below concentrations reported after single dosing studies and below those considered to be minimally inhibitory, death was presumed to have been caused by hypersensitivity and not an overdose. In conclusion, this procedure is useful for detecting and quantitating cefoperazone and sulbactam in postmortem blood and may be useful in the evaluation of anaphylaxis.

Cefoperazone is a third-generation cefalosporin that contains the N-methyl- thio-tetrazole (NMTT) side chain, which inhibits vitamin K-dependent carboxylation. Administration of NMTT-containing cefalosporins can cause alterations in the hepatic glutathione redox state, resulting in a dose-related increase in oxidised glutathione, which is responsible for the inhibition of microsomal reduction of vitamin K epoxide. In addition, cefoperazone is not metabolised and is excreted predominantly through the bile. In patients with hepatic impairment, the clearance of cefoperazone has been shown to be significantly reduced and the half-life prolonged. We report a case of choledocholithiasis related to a prolonged prothrombin time and INR secondary to cefoperazone therapy.

We report a case of an anaphylactic reaction due to a preoperatively administered antibiotic. A 72-year-old man scheduled to undergo cholecystectomy and choledocholithotomy received a cefoperazone infusion after being turned to a lateral position for insertion of an epidural catheter. Immediately after local injection of lidocaine, he, complained of inguinal itching. His systolic blood pressure then decreased to 60 mmHg and complained of discomfort and vomited. Soon, his systolic blood pressure decreased to 40 mmHg and he lost consciousness. Antibiotic infusion was stopped and he was returned to a prone, head-down position. His Spo2 decreased to 90%, and oxygen was administered. Following ephedrine 10 mg injection, his systolic blood pressure increased to 80 mmHg and he became conscious, but an erhythemic area appeared on his precordial region. Repeated epinephrine 0.05 mg injection restored his blood pressure to the preoperative level. Since a blood sample obtained 15 minutes after the event revealed high serum IgE levels, he was diagnosed as IgE-mediated anaphylactic reaction. Subsequent intradermal tests were tentatively positive to cefoperazone and negative to lidocaine. Surgery was successfully performed using cefotiam, which was also negative in a preoperative intradermal test.

A retrospective analysis of the clinical and microbiological efficacy and safety of cefoperazone/sulbactam in the treatment of 39 cardiosurgical patients operated under the conditions of artificial circulation is presented. The age of the adult patients (n = 28) varied from 44 to 58 years and that of the pediatric patients varied from 4 months to 6 years. Antibacterial therapy of 26 patients was needed because of postoperative infectious complications, such as nosocomial pneumonia in 22 patients and sepsis in 4 patients. The antibacterial therapy with cefoperazone/sulbactam in 9 patients was performed during the operation because of active infectious endocarditis. In 4 patients there were observed clinical and laboratory signs of infection without the infection foci. The initial empirical therapy with cefoperazone/sulbactam was applied to 14 patients (group 1) and the target-aimed therapy based on the data of the pathogen susceptibility to cefoperazone/sulbactam was used in 6 patients (group 2). 19 patients (group 3) were treated with cefoperazone/sulbactam because of the fail of the previous antibacterial therapy, including the 4th generation cephalosporins and carbapenems as well. Cefoperazone/sulbactam was used in the monotherapy of 15 cases (38%). Cefoperazone/sulbactam showed high efficacy in the treatment of severe nosocomial infections and infectious endocarditis (in combination with vancomycin or linezolid). It amounted to 93, 100 and 79% in groups 1, 2 and 3 respectively, the total of 94%. The results of the microbiological assay were evident of the cefoperazone/sulbactam high activity against the problem gram nagative isolates of Klebsiella pneumoniae (n = 12), Acinetobacter baumanii (n = 4), Pseudomonas aeruginosa (n = 4) and Stenotrophomonas maltophilia (n = 5). Adverse reactions were stated in 2 patients (5%), 1 case of urticaria requiring discontinuation of the drug use. Many of the patients proved to be colonized by MRS before the therapy with cefoperazone/sulbactam. The high probability of staphylococcal superinfection required combination of cefoperazone/sulbactam with antistaphylococcal agents, such as rifampicin, fusidin, vancomycin, linezolid. The best results were provided by the target-aimed therapy based on the microbiological monitoring.

Objective: To describe a case of cefoperazone-induced acute interstitial nephritis (AIN) in which the diagnosis was supported by renal biopsy., Case Summary: A 35-year-old woman presented to our hospital with decreased urine output and no past history of renal problems. Fifteen days prior to presentation, she had started treatment with intramuscular cefoperazone 1 g/day for a scalp infection. On day 12 of therapy, the patient noted decreased urine output, anorexia, and weakness, but she continued taking cefoperazone for 3 more days. Hemodialysis and oral prednisolone 1 mg/kg (30 mg twice daily) were started. Renal function returned to normal after 2 months of prednisolone treatment., Discussion: Although AIN has been linked with other cephalosporins, as of June 18, 2004, to our knowledge, this is the first report of a cefoperazone-induced case. We based our diagnosis on the features of acute-onset renal failure, abnormal urinalysis findings, eosinophilia, inflammatory infiltrate in the interstitium, and recovery from renal failure after initiation of corticosteroid treatment. Application of the Naranjo probability scale indicated a probable relationship between the acute renal failure secondary to the possible AIN and cefoperazone therapy in this patient., Conclusions: This case indicates that cefoperazone, like other cephalosporins, can cause AIN. We recommend close monitoring of renal function in patients who are prescribed this drug.

The use of cefoperazone/sulbactam in combination with amikacin in the treatment of 20 patients with mucoviscidosis and exacerbation of bronchopulmonary pathological process resulted in marked positive dynamics of the clinical and functional indices of the lungs state. The bacteriological effect with respect to the main pathogens in the cases of mucoviscidosis was strain-dependent: eradication of 10 (83.4%) out of 12 Staphylococcus aureus strains and only 3 (15.8%) out of 19 Pseudomonas aeruginosa strains. The most frequent adverse reaction was diarrhea (5 children) successfully corrigated by loperamide. Discontinuation of the drug use was required in 3 patients because of macrohematuria (1 child) and allergic eruption.

Recent studies have highlighted the emergence of infections involving multiresistant Acinetobacter clinical isolates. Sulbactam offers direct antimicrobial activity against Acinetobacter species. Accordingly, co-administration of sulbactam with ampicillin or cefoperazone offers the potential of effective empirical therapy against Acinetobacter and other bacteria such as Enterobacteriaceae in institutions in which they are susceptible. Many in vitro studies have indicated that Acinetobacter remains fully susceptible to ampicillin-sulbactam or cefoperazone-sulbactam. Furthermore, ampicillin-sulbactam has proven clinically effective and well tolerated in the treatment of severe acinetobacter infections, including bacteremia. Therefore, ampicillin-sulbactam is a sensible option for the treatment of life-threatening acinetobacter infections.

We report a case of anaphylactic reaction occurring during general anesthesia that may have been accompanied by a coronary artery spasm. The present case and a review of the medical literature suggest that coronary artery spasm is evoked by common vasoactive mediators with anaphylactic reactions. Coronary artery spasm should be counted as a symptom of the cardiovascular manifestation of anaphylaxis. Clinicians should be aware of this possible complication when treating an anaphylactic reaction, especially in patients at risk for atherosclerosis. Early recognition of ST segment elevation is essential for diagnosis and treatment of coronary artery spasm.

In a prospective, randomized, controlled trial, we compared sulbactam/cefoperazone with imipenem as empirical monotherapy for febrile, granulocytopenic patients; 101 patients received sulbactam/cefoperazone (2 g/4 g every 12 hours) and 102 patients received imipenem (500 mg every 6 hours). Documented infections were present in 40% of patients treated with sulbactam/cefoperazone (40 of 101) and in 39% of patients receiving imipenem (40 of 102). The number of pretherapy gram-positive pathogens (52 isolates) was twice the number of pretherapy gram-negative pathogens (26 isolates). The overall favorable clinical response rates for sulbactam/cefoperazone (91 of 103 patients, or 88%) and imipenem (84 of 104 patients, or 81%) were similar. Both drugs were generally well tolerated. However, diarrhea occurred more often in patients treated with sulbactam/cefoperazone (31 of 101 patients, or 31%, vs. 15 of 102 patients, or 15%; P = .007), while seizures developed only in patients receiving imipenem (0 of 101 patients vs. 3 of 102 patients, or 3%). Superinfections developed in 16% of patients in both study groups but were infrequently caused by beta-lactam-resistant gram-negative bacilli (two cases with sulbactam/cefoperazone therapy and six cases with imipenem). These results support the efficacy and safety of either sulbactam/cefoperazone or imipenem as empirical monotherapy for febrile granulocytopenic patients.