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Background: The preferred antibiotic salvage regimen for persistent methicillin-susceptible Staphylococcus aureus bacteremia (MSSAB) is unclear. Ertapenem with cefazolin or an antistaphylococcal penicillin has been primarily described, but identifying alternative carbapenem-sparing options may support antibiotic stewardship efforts and decrease the risk of antibiotic-associated Clostridioides difficile infection., Objective: We sought to evaluate the effectiveness and safety of daptomycin plus oxacillin (D/O) for persistent MSSAB., Methods: This was a single-center, retrospective cohort of patients with persistent MSSAB who received D/O between January 1, 2014, and January 1, 2023. Adult patients were included if they had blood cultures positive for MSSA ≥72 hours and received D/O combination for ≥48 hours. Patients were excluded if they were pregnant, incarcerated, or received another antibiotic considered to have excellent activity against MSSA. The primary outcome was time to MSSA bacteremia clearance post-daptomycin initiation. Secondary outcomes included microbiological cure, hospital length of stay, 90-day all-cause mortality, MSSA bacteremia-related mortality, 90-day readmission for MSSAB, and incidence of antibiotic-associated adverse effects. Time to MSSAB clearance post-D/O initiation was plotted using Kaplan-Meier estimation., Results: Seven unique patient encounters were identified including 4 with endocarditis. Despite a median MSSA bacteremia duration of 7.8 days, median clearance was 2 days post-daptomycin initiation. All achieved microbiological cure, and no adverse effects were reported. Ninety-day all-cause mortality, MSSAB-related mortality, and 90-day readmission for MSSAB occurred in 28.6%, 14.3%, and 14.3% of patients, respectively., Conclusions and Relevance: D/O was an effective, well-tolerated salvage regimen in this cohort and may represent a carbapenem-sparing option for persistent MSSAB., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Wesley D. Kufel has received research grants from Merck and Melinta and has served on the advisory board for Theratechnologies, Inc. Jeffrey M. Steele has served on the advisory board for Paratek Pharmaceuticals. All other authors have nothing to disclose.

Antistaphylococcal penicillins (ASP) and cefazolin are first-line treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. Borderline oxacillin resistance (i.e., oxacillin MICs 1-8 μg/mL) is observed in strains hyperproducing beta-lactamases. This mechanism is also behind the proposed inoculum effect. Minimal data exists on the comparative efficacy of cefazolin or ASP in qualitatively susceptible strains that demonstrate MICs of oxacillin of 1 to 2 μg/mL compared to strains with MIC of oxacillin < 1 μg/mL. We performed a retrospective cohort study of acute treatment outcomes in adult patients with community-acquired MSSA bacteremia treated with cefazolin or ASP, stratified by oxacillin MIC. The primary outcome was a composite of all-cause mortality during the index inpatient admission, failure to clear blood cultures within 72 h after initiating definitive therapy, and change in therapy due to perceived lack of efficacy. A total of 402 patients were included in this study, including 226 isolates with an oxacillin MIC ≥ 1 μg/mL and 176 isolates with an MIC < 1 μg/mL. There were no differences in the rate of the primary outcome occurrence between patients with an oxacillin MIC ≥ 1 μg/mL and an MIC < 1 μg/mL (16.4% versus 15.9%, P  = 0.90). There was no difference in the primary outcome between high versus low oxacillin MIC groups among those who received ASP (22.9% versus 24.1%, P  = 0.86) or cefazolin (10.3% versus 11.9%, P  = 0.86). In our cohort of patients with MSSA bacteremia, oxacillin MIC (i.e., ≥ 1 versus < 1 μg/mL) was not associated with acute treatment outcomes, regardless of the beta-lactam selected as definitive therapy.

Rationale: Drug-induced aseptic meningitis (DIAM) is an uncommon meningitis and trimethoprim with or without sulfamethoxazole is the most involved antibiotic. Although DIAM is easily treated with the discontinuation of the causative drug, the diagnosis is a big challenge for physicians, as it remains a diagnosis of exclusion. Here, we present a case report of trimethoprim-sulfamethoxazole induced aseptic meningitis in a woman with acute osteomyelitis., Patient Concerns: A 52-year-old woman was admitted to the hospital for septic shock and acute osteomyelitis of the right homerus. She was started on antibiotic therapy with oxacillin and daptomycin, then oxacillin was replaced with cotrimoxazole, due to its excellent tissue penetration, including bone tissue. During cotrimoxazole therapy, the patient developed a fluent aphasia with ideomotor apraxia and muscle hypertonus., Diagnosis and Interventions: Having excluded infectious, epileptic and vascular causes of the acute neurologic syndrome of our patient, given the improvement and full recovery after discontinuation of cotrimoxazole, we hypothesized a DIAM., Outcomes: After discontinuation of cotrimoxazole, in 48 hours the patient had a full recovery., Lessons: Although DIAM can be easily managed with the withdrawal of the causative drug, it can be difficult to recognize if it is not included in the differential diagnosis. An antimicrobial stewardship program with a strict monitoring of patients by infectious disease specialists is essential, not only to optimize the appropriate use of antimicrobials, but also to improve patient outcomes and reduce the likelihood of adverse events., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Anti-staphylococcal penicillins (ASPs) are among the most commonly prescribed antibiotics in children and are associated with a risk of drug-induced liver injury (DILI). Despite the frequent use of ASPs in children, there is no consensus on whether liver function tests (LFTs) should be routinely monitored during treatment., Objectives: To review the literature on the frequency of ASP-related DILI in children to determine the incidence, risk factors and outcomes of hepatotoxicity., Methods: PubMed, MEDLINE and Embase were searched in January 2022 for original studies of children who received cloxacillin, dicloxacillin, flucloxacillin, methicillin, nafcillin or oxacillin that included ≥10 children aged up to 18 years, and presented data on the incidence of DILI in children exposed to ASPs., Results: Overall, two studies of oral flucloxacillin, two of intravenous (IV) methicillin, three of IV nafcillin and four of IV oxacillin were included. The mean onset of DILI ranged between 7.0 and 19.0 days following commencement of antibiotic treatment and all episodes resolved between 14.2 and 16.0 days after drug discontinuation, with no specific treatment required. This review found that the incidence of DILI in children was 1 in 50 000 for oral flucloxacillin and ranged from 1 in 3 to 13 for IV oxacillin, methicillin and nafcillin., Conclusions: This review found that routine LFT monitoring is not required in children receiving low dose oral flucloxacillin in a primary care setting, although pharmacovigilance is critical. For IV preparations, the existing data support routine LFT monitoring in those receiving treatment for at least 7 days., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Background: Drug reaction with eosinophilia and systemic symptoms syndrome is a rare but severe and potentially life-threatening hypersensitivity reaction, with significant morbidity and mortality. The clinical presentation of drug reaction with eosinophilia and systemic symptoms may include extensive skin rash, fever, lymphadenopathy, internal organ involvement, eosinophilia, and atypical lymphocytosis, most commonly due to drug-induced reaction. Our case is a rare occurrence of drug reaction with eosinophilia and systemic symptoms syndrome in the setting of oxacillin therapy., Case Presentation: A 55-year-old Caucasian male presented to the emergency department on account of acute onset, 2-day history of generalized pruritic rash with associated fever, occurring 3 weeks after commencing therapy with intravenous oxacillin for methicillin-sensitive Staphylococcus aureus bacteremia. He had no known drug allergies. Two days prior to hospitalization, he had a telehealth visit with the infectious diseases specialist on account of his rash, and was recommended to use oral diphenhydramine. However, with the onset of fever and persistence of his rash, he was advised to discontinue the oxacillin and present to the emergency department. On examination, he was febrile at 101.2 °F and had a generalized blanchable maculopapular and morbilliform rash involving the face, trunk, upper and lower extremities, but sparing the palms, soles, and oral mucosa. He had palpable nontender lymph nodes in the cervical and inguinal regions bilaterally. Laboratory studies revealed atypical lymphocytosis, eosinophilia, neutrophilia, and elevated serum transaminases. He was started on intravenous diphenhydramine and admitted to the in-patient medical service. On the second day of hospitalization, his fever resolved. However, his rash was persistent and generalized, as well as elevated transaminases and an abnormal cell count on the second day of hospitalization. To complete his 6-week course of antibiotics for methicillin-sensitive Staphylococcus aureus bacteremia, he was switched to an alternative therapy with cefazolin, and he was scheduled for weekly follow-up assessments following hospital discharge., Conclusions: Healthcare providers should increasingly be aware of the significant morbidity and mortality attributable to drug reaction with eosinophilia and systemic symptoms syndrome and the potential medications which may incite such life-threatening reactions. Early recognition of drug reaction with eosinophilia and systemic symptoms syndrome and prompt institution of management strategies can promote improved clinical outcomes. Enhanced patient-provider communication strategies should be implemented to better prepare patients for the likelihood of such drug reactions, with the goal of improving patient-centered care and adherence with treatment strategies., (© 2021. The Author(s).)

Antistaphylococcal penicillins such as nafcillin and oxacillin are among the first choices of treatment for severe invasive methicillin-susceptible Staphylococcus aureus (MSSA) infections, although there has been limited safety evaluations between individual agents. Using the FDA Adverse Event Reports System (FAERS), oxacillin was observed to have a lower proportion of reports of acute renal failure (reporting odds ratio [ROR], 5.3 [95% confidence interval {CI}, 3.1 to 9.3] versus 21.3 [95% CI, 15.8 to 28.6], respectively) and hypokalemia (ROR, 0.7 [95% CI, 0.1 to 4.8] versus 11.4 [95% CI, 7.1 to 18.3], respectively) than nafcillin., (Copyright © 2020 American Society for Microbiology.)

BACKGROUND Drug reaction with eosinophilia and systemic symptoms (DRESS) is an idiosyncratic life-threatening reaction comprised of fevers, rash, and leukocytosis with eosinophilia. Though characteristically associated with leukocytosis, there are rare case reports of DRESS-induced agranulocytosis. DRESS is most frequently caused by antiepileptic medications; however, it has very rarely been reported in relation to oxacillin. We describe a case of oxacillin-induced DRESS associated with agranulocytosis. CASE REPORT A 52-year-old male was admitted for an epidural abscess secondary to oxacillin-sensitive Staphylococcus aureus, for which an extended course of oxacillin and rifampin was initiated. On day 22 of therapy, the patient developed a fever of 38.7°C (101.6°F) with rigors. His complete blood cell count revealed new leukopenia (1.8×10³/uL) with 16% eosinophils and 3% atypical lymphocytes. Antibiotics were transitioned from oxacillin and rifampin to vancomycin, cefepime, and rifampin for presumed sepsis of unclear etiology. On day 23, he was noted to have a pruritic erythematous blanching papular rash on his chest, trunk, neck, and left upper extremity. Infectious workup was unrevealing, and his fever curve up-trended to 39.3°C (102.7°F) with no clinical improvement on broad-spectrum antimicrobials, suggestive of a non-infectious etiology of his rash and fevers. His rash evolved into confluent red patches, and eosinophilia rose to 21%, which was concerning for a drug reaction. His RegiSCAR score was calculated to be 6, consistent with definite DRESS. Leukopenia resolved (6.3×10³/uL) 4 days after discontinuing oxacillin. His epidural abscess was ultimately treated with daptomycin, and DRESS was managed supportively with antihistamines and triamcinolone cream. CONCLUSIONS We highlight this case because of the rarity of DRESS with agranulocytosis related to oxacillin. Beta-lactam antibiotics are widely used, and while DRESS is an uncommon condition, clinicians should consider this diagnosis when managing patients with fevers, leukopenia, and rash.

Nafcillin and oxacillin are used interchangeably in clinical practice, yet few studies have evaluated the safety of these two agents. Our objective was to compare the differential tolerabilities of nafcillin and oxacillin among hospitalized patients. We conducted a retrospective cohort study of all patients who received 12 g/day of nafcillin or oxacillin for at least 24 h. Two hundred twenty-four patients were included. Baseline characteristics and comorbidities were similar among patients receiving nafcillin (n = 160) and those receiving oxacillin (n = 64). Hypokalemia, defined as a potassium level of ≤3.3 mmol/liter or ≤2.9 mmol/liter or as a ≥0.5-mmol/liter decrease from the baseline level, occurred more frequently among patients who received nafcillin (51%, 20%, and 56%, respectively) than among those who received oxacillin (17%, 3%, and 34%, respectively; P < 0.0001, P = 0.0008, and P = 0.005, respectively). By multivariate logistic regression analysis, receipt of nafcillin was an independent predictor of severe hypokalemia (odds ratio [OR] = 6.74; 95% confidence interval [CI], 1.46 to 31.2; P = 0.02). Rates of hepatotoxicity did not differ between groups; however, acute kidney injury occurred more commonly with nafcillin than with oxacillin (18% versus 6%; P = 0.03). Overall, 18% of patients who received nafcillin discontinued therapy prematurely due to adverse events, compared to 2% of patients who received oxacillin (P = 0.0004). Nafcillin treatment is associated with higher rates of adverse events and treatment discontinuation than oxacillin among hospitalized adult patients. These findings have important implications for patients in both inpatient and outpatient settings, particularly patients who require long-term therapy and cannot be monitored routinely. Future randomized controlled studies evaluating the efficacy, costs, and tolerability of nafcillin versus oxacillin are warranted., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Herein we present a case of a 9-month-old boy admitted to our hospital for acute femoral osteomyelitis and hip septic arthritis treatment. Acute hepatitis with concomitant skin rash developed on the sixth day of intravenous oxacillin therapy. No other known virus- or drug-related skin eruption or hepatitis was suspected. The boy recovered completely after antibiotics were shifted to teicoplanin, and no sequelae were noted. To our knowledge, this boy is the youngest case of reported oxacillin-related hepatitis in the literatures.

A 6-year-old girl had fever, abdominal pain, and severe anicteric hepatitis during intravenous oxacillin therapy for staphylococcal osteomyelitis. She had greatly elevated liver enzymes, prolonged prothrombin time, leukopenia, and eosinophilia. Clinical symptoms resolved and laboratory data returned to normal after withdrawing oxacillin and substituting cefazolin. This hepatotoxicity appears to be specific to oxacillin and not to other beta-lactams. Monitoring liver function tests during oxacillin therapy, especially in patients receiving prolonged treatment, may be warranted.

This study compared adverse drug reactions (ADRs) to oxacillin with those to nafcillin and other antibiotics. We reviewed the medical records of 222 children receiving outpatient parenteral antimicrobial therapy (OPAT) from February 1995 through June 1999. The diagnosis, antibiotics used, ADRs, action taken, and patient demographics were recorded. The most common ADRs were neutropenia (9.8%), rash (8.5%), and hepatotoxicity (3.8%). ADRs occurred more frequently in the oxacillin group (58.5%) than in the nafcillin group (29.3%; P=.004), the clindamycin group (12.5%; P<.001) and the "other" antibiotics group (14.4%; P<.001). Hepatotoxicity and rash occurred more frequently in the oxacillin group (22% and 31.7%, respectively) than in the nafcillin group (0% [P<.001] and 10.3% [P=.008]), the clindamycin group (1.4% [P<.001] and 8.3% [P=.001]), and the other antibiotics group (1.4% [P<.001] and 1.4% [P<.001]). On the basis of this retrospective analysis, oxacillin use in children was associated with a higher incidence of hepatotoxicity and rash, compared with the use of nafcillin and other intravenous antimicrobials.

A 67-year-old man who was treated with oxacillin for one week because of Staphylococcus aureus bacteremia, developed renal failure and diffuse, symmetric, palpable purpuric lesions on his feet. Necrotic blisters were noted on his fingers. Skin biopsies showed findings diagnostic of leucocytoclastic vasculitis. Oxacillin was discontinued and patient was treated with corticosteroids. The rash disappeared after three weeks and renal function returned to normal. Leucocytoclastic vasculitis presents as palpable purpura of the lower extremities often accompanied by abdominal pain, arthralgia, and renal involvement. Etiologic factors or associated disorders include infections, medications, collagen vascular disease and neoplasia. However, in half of the cases no etiologic factor is identified. Usually it is a self-limited disorder, but corticosteroid therapy may be needed in life-threatening cases since early treatment with corticosteroids in severe cases can prevent complications. Oxacillin should be included among the drugs that can cause leucocytoclastic vasculitis.

This randomized, double-blind, multicenter trial compared the efficacy and safety of linezolid, an oxazolidinone, with those of oxacillin-dicloxacillin in patients with complicated skin and soft tissue infections. A total of 826 hospitalized adult patients were randomized to receive linezolid (600 mg intravenously [i.v.]) every 12 h or oxacillin (2 g i.v.) every 6 h; following sufficient clinical improvement, patients were switched to the respective oral agents (linezolid [600 mg orally] every 12 h or dicloxacillin [500 mg orally] every 6 hours). Primary efficacy variables were clinical cure rates in both the intent-to-treat (ITT) population and clinically evaluable (CE) patients and microbiological success rate in microbiologically evaluable (ME) patients. Safety and tolerability were evaluated in the ITT population. Demographics and baseline characteristics were similar across treatment groups in the 819 ITT patients. In the ITT population, the clinical cure rates were 69.8 and 64.9% in the linezolid and oxacillin-dicloxacillin groups, respectively (P = 0.141; 95% confidence interval -1.58 to 11. 25). In 298 CE linezolid-treated patients, the clinical cure rate was 88.6%, compared with a cure rate of 85.8% in 302 CE patients who received oxacillin-dicloxacillin. In 143 ME linezolid-treated patients, the microbiological success rate was 88.1%, compared with a success rate of 86.1% in 151 ME patients who received oxacillin-dicloxacillin. Both agents were well tolerated; most adverse events were of mild-to-moderate intensity. No serious drug-related adverse events were reported in the linezolid group. These data support the use of linezolid for the treatment of adults with complicated skin and soft tissue infections.

Objective: To report a case of oxacillin-induced tissue necrosis in which recommended concentration guidelines for dilution and administration were used. Oxacillin concentration data, potential risk factors, and treatment options for extravasation injuries are also briefly reviewed., Case Summary: Oxacillin was infused peripherally by infusion pump in a 79-year-old white woman as prophylactic antibiotic coverage for permanent pacemaker placement. Oxacillin extravasation occurred after the second postoperative dose. A dime-sized area of necrosis was noted at the heparin-lock insertion site., Discussion: Only one case of oxacillin-induced necrosis has been reported. The degree of damage and concentration of drug used were not specifically described. Concentration may play a role in the appearance or absence of tissue damage after an antibiotic extravasation and should be taken into consideration when evaluating a drug's tissue toxicity potential., Conclusions: The potential exists for oxacillin 50 mg/mL to cause tissue damage in humans if an extravasation occurs. This reaction may be avoided with use of a less-concentrated preparation, avoidance of infusion pump administration, and identification of high-risk patients.

Teratogenic studies of oxacillin in humans have not been published. The population-based data-set of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996 contains 22,865 foetuses or newborns with congenital abnormalities and 38,151 matched control newborns without congenital abnormalities. The mothers of 14 cases and 19 controls were treated with oral oxacillin during pregnancy. A teratogenic risk of oxacillin was not detected in this case-control study.

Animal experiments demonstrate that gentamycin, kanamycin and carbenicillin affect lipid peroxidation in the kidneys. This can be registered by chemiluminescence of renal and urinary homogenates. This phenomenon was also used in functional examination of the kidneys in 161 neonates treated by antibiotics. The earliest renal dysfunctions due to nephrotoxicity were detected by chemoluminescence induced by ions of bivalent iron. The method is simple and rapid, this making it convenient in neonatal practice for detection of nephropathy before the symptoms presentation.

Documented adverse reactions to anti-infective agents in patients of a home infusion company were studied to determine whether the prevalence of reactions was greater in patients receiving nafcillin or oxacillin than in those receiving other i.v. antiinfectives. Data on adverse drug reactions (ADRs) were obtained by reviewing the discharge summaries of all patients who received anti-infective therapy in 1990-1994 and the company's quarterly and annual ADR reports for that period. The occurrence of ADRs per total courses of therapy was calculated for groups of antiinfectives, as were intensity and causality. For ADRs to nafcillin and oxacillin, patient demographics and treatment information and outcomes were reviewed. A total of 2488 courses of anti-infective therapy were documented, and ADRs occurred in 10.9%. Nafcillin and oxacillin accounted for 105 courses, with an ADR rate of 31.4%; 99 patients received one of these drugs and 24 had ADRs, with rash and phlebitis the most common ADRs. Thirty-nine patients receiving nafcillin or oxacillin had documented infection with methicillin-sensitive Staphylococcus aureus. Seventy-five patients receiving nafcillin or oxacillin did not have an ADR; therapy was successful in 62 of these patients. Of the 24 patients with ADRs to nafcillin or oxacillin, 13 were switched to other i.v. anti-infectives, which were successful in 10 of them. Five patients were hospitalized because of ADRs to nafcillin or oxacillin. Most nafcillin or oxacillin ADRs that resulted in a therapy change or hospitalization occurred in the second or third week of therapy. Home care patients who received nafcillin or oxacillin therapy had a disproportionately high number of ADRs, compared with patients who received other anti-infective agents.

The possibility of the correction of intestinal microflora disorders and the functional activity of macrophages in dysbiosis, caused by the intragastric administration of ampiox, with the use of amben (PAMBA), an inhibitor of proteolytic enzymes, was studied. Quantitative and qualitative changes in the main representatives of automicroflora, the functional activity of macrophages in the phagocytosis of 51Cr-labeled sheep red blood cells, the intensity of protein synthesis, the content of cathepsin D, acidic phosphatase and nitro blue tetrazolium activity were determined. The combined administration of ampiox and amben normalized quantitative and qualitative ratios of the main representatives of intestinal microflora, as well as the characteristics of macrophage functional activity, studied in this investigation. The administration of amben to intact animals was found to stimulate bifido- and lactoflora.

An open, comparative, randomized study was performed in two medical intensive care units to compare the efficacy of the combination of aztreonam and either cloxacillin or oxacillin [(cl)oxacillin] with that of the combination of tobramycin and a cephalosporin. Of the 92 patients who were included in the study, 76 were evaluable. All patients suffered from severe, mostly pulmonary, infections and received ventilatory support. The aztreonam combination yielded an 80% rate of clinical cure; mortality was 15%. Use of the aminoglycoside combination resulted in a 51% rate of clinical cure; mortality was 23%. The difference in cure rate between the two combinations was statistically significant. Adverse effects were negligible in patients who received the aztreonam combination, and superinfection was seen in only 2%. Of the patients who received the aminoglycoside combination, 20% developed a superinfection and 11% developed a new renal insufficiency. Therefore, the combination of aztreonam and (cl)oxacillin is a valuable alternative to the combination of an aminoglycoside and a cephalosporin.

Pseudomembranous colitis has been reported as a complication of therapy with a number of different antibiotics. We present here a case of pseudomembranous colitis following therapy with oxacillin, in which the causative organism and the toxin it produces were isolated from the patient's stool. We believe this is the first documented case of oxacillin-induced pseudomembranous colitis.

68 patients (from newborns to 18 years of age) were studied prospectively for adverse effects associated with methicillin, nafcillin and oxacillin. Hematologic, liver and renal function tests were monitored before and during therapy. 3 of 28 patients receiving methicillin developed eosinophilia within 5-8 days. Of 32 patients on nafcillin, 2 had neutropenia within 4-13 days, 3 had eosinophilia within 1-4 days and 1 elevated liver enzymes on day 3. Of 8 patients receiving oxacillin, 1 developed neutropenia on day 11 and another showed elevation of liver enzymes on day 15. All abnormalities were reversible with the discontinuation of therapy. Appropriate laboratory tests should be monitored to detect an occurrence of adverse reaction to methicillin, nafcillin and oxacillin.

The semisynthetic penicillins, like the parent drug penicillin G, are remarkably safe drugs. However, a significant number of patients have been reported in whom profound neutropenia has developed. This is a side effect of these drugs not appreciated by a significant number of physicians. I report two more cases of neutropenia due to nafcillin and review the literature on neutropenia induced by semisynthetic penicillin. The relative risk of each individual drug is evaluated, and the two proposed mechanisms of production of the neutropenia are discussed.

Four children had cutaneous necrosis associated with the administration of intravenous (IV) nafcillin sodium therapy. One patient required skin grafting. Hospitalization was prolonged with this patient and with one other in an effort to ensure healing. Adult rats, inoculated subcutaneously with nafcillin that was appropriately diluted according to manufacturer's recommendations, exhibited similar lesions. Oxacillin sodium, methicillin sodium, and cephalothin sodium, similarly diluted, did not necrose skin. Nafcillin should be added to the list of agents that produce similar toxic conditions. Frequent observation of the IV infusion site to detect extravasation may obviate this hazard.

The development of granulocytopenia during oxacillin therapy is reported in 2 patients. In both cases the onset of granulocytopenia occurred 24 days after therapy was instituted with similar clinical presentations. The bone marrow aspirates revealed myeloid hyperplasia, left shift and maturation arrest. 24 h after oxacillin was discontinued the granulocyte counts rapidly rose towards normal, with subsequent complete recovery. Although sought for, leukoagglutinins could not be demonstrated in either patient. The occurrence of granulocytopenia in patients receiving natural and semisynthetic penicillins is reviewed and the mechanisms are outlined.

Neutropenia developed in 3 pediatrics patients during treatment with oxacillin. The time of onset ranged from 18 to 24 days after beginning treatment with dose of 150 mg/kg/24 h. Concomitant symptoms were fever and rashes. During treatment with oxacillin it is necessary to monitor blood cell count every week.

An instance of profound neutropenia secondary to oxacillin which resolved rapidly on withdrawal of the drug was reported. It was accompanied by eosinophilia. Although the bone marrow findings were indicative of destruction of granulocytes in the periphery, antibody could not be demonstrated.

We have reported a rare case of oxacillin-associated pseudomembranous colitis in which great difficulty was experienced in successfully isolating the organism in a routine hospital laboratory, resulting in delay in treatment. Toxin assay done at a reference laboratory finally allowed successful treatment. Toxin assay can be valuable in the diagnosis and management of this potentially serious illness.

Hepatotoxicity, in association with intravenous oxacillin therapy, is described and documented for the first time by liver biopsy in an illicit drug user suffering from acute staphylococcal endocarditis. Mild gastrointestinal symptomatology, fever, eosinophilia and abnormal liver enzyme abnormalities were noted. Liver biopsy showed features consistent with a drug-induced hepatic injury. Cessation of therpy led to rapid reversal of clinical and biochemical changes and on further observation no evidence of chronic hepatic dysfunction was noted. A brief review of oxacillin hepatic injury is presented.

Acute interstitial nephritis secondary to administration of antibiotics is a well-described entity. Oxacillin, however, has never been directly implicated. An 80-year-old man had a rising creatinine level and eosinophiluria while receiving oxacillin sodium. These findings disappeared when use of the drug was discontinued. We conclude that oxacillin is an additional penicillin that can cause interstitial nephritis.

For diagnosis of drug allergy and antibiotic allergy in particular it is necessary to use several cell reactions in combination in vitro and to estimate them in complex with clinical data. To obtain reliable results it is recommended to observe the conditions of choosing the time of the test, antibiotic optimal concentrations and pH 6.8.

An elderly woman was admitted for treatment of severe stasis ulceration, associated with varicose veins. One course of cloxacillin was given orally followed by a second course of penicillin-G to eradicate persistant hemolytic streptococcal skin infection. Deep progressive jaundice subsequently developed due to intrahepatic cholestasis and persisted for several weeks before resolution. Having excluded a progressive extrahepatic malignant lesion by appropriate investigations, the diagnosis was substantiated by classical changes present in a percutaneous liver biopsy.

When patients allergic to penicillin develop life-endangering infections that require treatment with beta-lactam antibiotics, they face a fatal infection or the possibility of a fatal allergic reaction. We have approached this situation by using an oral desensitization procedure before full-dose antibiotic therapy. Thirty consecutive patients with histories of allergic reactions to penicillin, positive immediate wheal and flare skin-test reactions to penicillin determinants, and life-threatening infections were studied. Bacterial endocarditis requiring penicillin G therapy led to desensitization of 19 patients, Pseudomonas sepsis of pneumonia requiring treatment led to desensitization of nine subjects, and staphylococcal infections requiring therapy with a penicillinase-resistant penicillin led to desensitization of two patients. Penicillin G or carbenicillin were administered orally, beginning with 100 U or 60 microgram, respectively. At 15-min intervals, progressively doubled doses were given during continuous monitoring for the appearance of allergic reactions. Within 5 hr, full therapeutic doses were administered intravenously. Skin-test reactions disappeared or diminished in all 23 subjects who were retested after desensitization. Full courses of antibiotic therapy and cure of the infections were accomplished in 30 of 30 patients. No deaths, anaphylaxis, or severe acute allergic reactions occurred. Pruritic cutaneous eruptions appeared in nine patients (30%) 6 to 48 hr after the onset of therapy. One patient developed reversible nephritis 3 wk into therapy with penicillin G. The results of this study suggest that oral desensitization is an effective, relatively safe approach to administering beta-lactam antibiotics to penicillin-allergic patients with life-threatening infections.

Severe bacterial infections accompanying conditions during childhood which demand for surgical intervention mostly are caused by Staph. aureus, E. coli, Klebsiella/Aerobacter or Ps. aeruginosa. 20 patients, 10 of them suffering from a putrid peritonitis, showed a good efficacy of Optocillin (Bay 1-1330), a combination of 6-((R)-2-[3-methylsulfonyl-2-oxo-imidazolidine-1-carboxamido]-2-phenyl-acetamido)-penicillanic acid sodium salt (mezlocillin, Baypen) and 5-methyl-3-phenyl-4-isoxazolylpenicillin (oxacillin, Stapenor), in 85%. Bacteria were eliminated in 79%.

A retrospective review of all patients who received oxacillin intravenously in doses greater than 6 g/day was done. Eight patients in whom oxacillin-associated hepatitis developed were found and compared with a control group of 46 patients who had received high-dose oxacillin and in whom oxacillin-associated hepatitis did not develop. The latent period to development of typical symptoms of hepatitis varied from 2 to 21 days. Laboratory abnormalities were compatible with anicteric hepatitis and reverted to normal after withdrawal of the drug. Oxacillin hepatitis most like represents a hypersensitivity reaction. We recommend that routine liver chemistries be done regularly in all patients receiving high-dose intravenous oxacillin.

Oxacillin-induced neutropenia is reported in a 16-year-old boy being treated for osteomyelitis. The startling neutropenia developed after 20 days of 200 mg/kg/day of intravenous oxacillin. The neutropenia was not associated with symptoms and was rapidly reversible upon stopping the antibiotic. This reaction may happen with any of the betal lactam antibiotics and is believed to be a direct toxic effect on white cell precursors in the bone marrow.