A RANDOMISED TRIAL OF EMPIRICAL ANTIBIOTIC THERAPY IN FEBRILE NEUTROPENIC PATIENTS WITH HEMATOLOGICAL DISORDERS: CEFTAZIDIME VERSUS AZLOCILLIN PLUS AMIKACIN

One hundred and two patients with neutropenia (<1 × 10⁹/L) secondary to primary hematological disorders or chemotherapy for hematological malignancies were prospectively randomised, upon the development of fever or other signs of infection, to receive empirical antibiotic treatment with either ceftazidime (± flucloxacillin) (n = 52) or azlocillin plus amikacin (± flucloxacillin) (A&A, n = 50). The two groups were equivalent with respect to clinical and laboratory parameters prior to antibiotic therapy and flucloxacillin was added to approximately 25% of the patients in each group on the clinical suspicion of Gram positive infection. When assessed at 96 hours, the complete response rates were 59.6% for the ceftazidime treated patients and 44% for A&A treated patients. Partial response rates were 17% and 20% respectively. This difference was not statistically significant. Eight patients died whilst on the trial, three of those initially randomised to ceftazidime and five initially randomised to A&A. Moderate to severe hypokalemia was encountered significantly less often in the ceftazidime treated group (p< 0.01), whilst other parameters of toxicity were equivalent. No primary or acquired resistance to ceftazidime was encountered. Separate analysis of those patients who did not receive flucloxacillin yielded identical results. We conclude that ceftazidime (±flucloxacillin) is as efficacious as azlocillin plus amikacin (±flucloxacillin) in the empirical antibiotic management of such patients and is associated with a lower incidence of moderate to severe hypokalemia.     

Uncovering a rare but critical complication following thyroid surgery: an audit across the UK and Ireland.

OBJECTIVE: Serious wound infection after thyroidectomy is uncommon, but actual incidence is not well documented in the literature. In the past a patient in our unit died secondary to fulminant streptococcal sepsis after thyroidectomy for benign disease. This prompted us to audit experience of serious wound infection among British Association of Endocrine Surgery (BAES) members. DESIGN: A questionnaire was posted to BAES members inquiring about experience of major wound infection following cervicotomy, incidence of minor wound infection, and prophylactic and therapeutic antibiotic usage. MAIN OUTCOME: Eight respondents experienced a case of fulminant wound infection after cervicotomy (8% total respondents). Five patients died and, in 6 patients, cases of streptococci were cultured. Then, 9% of respondents used prophylactic antibiotics routinely, 16% sometimes and 75% never. The most commonly used antibiotic was augmentin, and the most common reasons for use among those with a selective policy were re-operative cases (38%) and immunocompromised patients (38%). Also, 40% of respondents experienced major wound infection requiring intravenous antibiotics or surgical drainage. The most common choices of antibiotic used before sensitivities were obtained were augmentin (43%) and flucloxacillin (35%). CONCLUSIONS: Although rare, fulminant streptococcal wound infection after cervicotomy does occasionally occur and carries a high mortality.     

Prophylactic antibiotics for cardiac pacemaker implantation. A prospective trail.

A prospective trial was conducted to assess the value of prophylactic antibiotic treatment in preventing postoperative infection of permanent transvenous pacemaker systems. Four hundred and thirty-one patients were randomly allocated to treatment (234) or no-treatment (197) groups. Treated patients received systemic benzylpenicillin and flucloxacillin just before operation and one and six hours afterwards. Nine primary generator pocket infections occurred without evidence of wound dehiscence or skin erosion. Seven infections were in untreated patients and two in treated patients. Antibiotic prophylaxis diminishes the risk of infection after pacemaker implantations.     

Persistent Wound Infection after Herniotomy Associated with Small-Colony Variants of Staphylococcus aureus

Summary A small-colony variant (SCV) of Staphylococcus aureus was cultured from a patient with a persistent wound infection (abscess and fistula) 13 months after herniotomy. The strain was nonhemolytic, nonpigmented and grew only anaerobically on Schaedler agar. As it was coagulase-negative, it was initially misidentified as a coagulase-negative Staphylococcus. In further analysis, however, the microorganism was shown to be an auxotroph that reverted to normal growth and morphology in the presence of menadione and hemin (Schaedler agar) and could be identified as a SCV of Staphylococcus aureus. Surgery and antibiotic treatment of the patient with flucloxacillin and rifampicin for 4 weeks resulted in healing of the chronic wound infection. Received: April 19, 1999 · Revision accepted: December 1, 1999     

Flucloxacillin–warfarin interaction: an under‐appreciated phenomenon

Current drug databases do not acknowledge an interaction between warfarin and flucloxacillin although case reports have indicated that flucloxacillin may increase warfarin requirement to maintain therapeutic international normalised ratio (INR). To assess whether flucloxacillin therapy leads to a significant increase in warfarin dose, we conducted a retrospective, observational, cohort study of hospital‐in‐the‐home patients previously stable on warfarin; who were treated with flucloxacillin or other antibiotics for at least 2 weeks between June 2015 and December 2016. The outcome measured was change in average warfarin dose at two time periods: 1 week prior to antibiotic treatment and the final week of antibiotic treatment. Four cases with flucloxacillin and four comparators treated with other antibiotics met inclusion criteria. All cases treated with flucloxacillin had a clinically and statistically significant increase in warfarin dose in the final week of antibiotic treatment compared with pre‐antibiotics. The warfarin dose increased by a range of 57–130% (P < 0.05). There was no significant change in warfarin dose for patients on vancomycin, benzylpenicillin or piperacillin‐tazobactam. One comparator on cephazolin had a statistically significant change in warfarin dose; however, they had a sub‐therapeutic INR on admission which warranted a dose increase. Due to the high risk of sequelae with sub‐therapeutic anticoagulation, close INR monitoring is essential for patients on a prolonged course of flucloxacillin.     

A current approach to diabetic foot infections

Foot infections are a common, complex, and serious problem in diabetic patients. Infections usually begin in foo ulcers, which are associated with neuropathy, vasculopathy, and various metabolic disturbances. These infections are potentially limb and sometimes life threatening. Etiologic agents are usually aerobic gram-positive cocci, but chronic or serious infections often contain gram-negative rods and anaerobes. Chronic infections can lead to contiguous bone infection. Diagnosing osteomyelitis may require imaging studies (especially magnetic resonance imaging) and occasionally bone biopsy. In addition to proper cleansing, debridement, and local wound care, diabetic foot infections require carefully selected antibiotic therapy. Serious infections necessitate hospitalization for initial parenteral broad-spectrum antibiotic therapy, but appropriately selected patients with mild infections can be treated as outpatients with oral (or even topical) agents. Initial antibiotic selection is usually empiric; modifications may be needed based on the results of properly obtained cultures and the clinical response. Therapy should be active against staphylococci and streptococci, with broader-spectrum agents indicated if polymicrobial infection is likely. Levels of most antibiotics, except fluoroquinolones, are often subtherapeutic in infected foot tissues. The duration of therapy ranges from a week (for mild soft tissue infections) to over 6 weeks (for osteomyelitis). No single antibiotic agent or combination has proven to be optimal. With appropriate local, surgical, and antimicrobial therapy, most diabetic foot infections can now be successfully treated.     

Antibiotic Treatment for Uncomplicated Neuropathic Forefoot Ulcers in Diabetes: a Controlled Trial

To investigate the effect of oral antibiotics in purely neuropathic ulcers (Wagner grade 1–2, no osteomyelitis), a double blind placebo-controlled study was performed. Forty-four patients were enroled and subjected to standard treatment with absolute pressure relief (half shoes), daily wound cleansing (topical disinfectant), sterile dressings (specialized nurse). Patients were randomized to an antibiotic (amoxicillin plus clavulanic acid), or placebo. The study was stopped when the antibiotic proved unsuitable according to swab result, or on clinical grounds (no improvement within 6 days of recruitment). Main outcome measure was the ulcer closing rate during 20 days, as assessed by standardized photographs. All ulcers except one were infected. Of the placebo group (n = 22), 2 patients had to be withdrawn within 6 days, versus 3 patients of the antibiotic-group (n = 22). In the placebo group, 10 ulcers were healed versus 6 ulcers in the antibiotic group (NS). Mean (95% CI) reduction in ulcer radius was 0.41 (0.21–0.61) mm day⁻¹ in the placebo group versus 0.27 (0.15–0.39) mm day⁻¹ in the antibiotic group (NS). In conclusion, there is no benefit from antibiotic treatment with amoxicillin plus clavulanic acid as a supplement to standard therapy in uncomplicated neuropathic foot ulcers, provided pressure relief is complete, and wound care is performed strictly supervised. However, a Type-II statistical error cannot be excluded in this small study.     

Oral cefixime is similar to continued intravenous antibiotics in the empirical treatment of febrile neutropenic children with cancer.

Empiric oral antibiotic therapy for febrile neutropenic cancer patients has been suggested as a means to decrease hospitalization, but the safety of this approach has not been adequately studied in children. We compared continued iv antibiotic therapy with switching treatment to orally administered cefixime in a group of selected febrile neutropenic children for whom blood cultures were sterile after 48 h of incubation. Two hundred episodes of febrile neutropenia were studied (156 patients), and 100 episodes were randomized to receive each treatment. Failure to respond to therapy was defined by documented or suspected bacterial infection, recurrent fever, or discontinuation of assigned therapy for any reason before neutropenia resolved. Rates of treatment failure were similar in the oral cefixime group (28%) and in the iv antibiotic group (27%; P=1.0). Results support the safety of oral cefixime therapy for low-risk febrile neutropenic children, a therapeutic approach that would facilitate earlier outpatient management and decrease the costs of treatment.     

Clostridium difficile colitis in lung transplantation

Purpose. Clostridium difficile colitis (CDC) is the most common nosocomial infection of the gastrointestinal tract in patients with recent antibiotic use or hospitalization. Lung transplant recipients receive aggressive antimicrobial therapy postoperatively for treatment and prophylaxis of respiratory infections. This report describes the epidemiology of CDC in lung recipients from a single center and explores possible associations with bronchiolitis obliterans syndrome (BOS), a surrogate marker of chronic rejection.
Methods. Patients were divided into those with confirmed disease (CDC+) and those without disease (CDC−) based on positive C. difficile toxin assay. Because of a bimodal distribution in the time to develop CDC, the early postoperative CDC+ group was analyzed separately from the late postoperative CDC+ cohort with respect to BOS development.
Results. Between 1990 and 2005, 202 consecutive patients underwent 208 lung transplantation procedures. Of these, 15 lung recipients developed 23 episodes of CDC with a median follow-up period of 2.7 years (range, 0–13.6). All patients with confirmed disease had at least 1 of the following 3 risk factors: recent antibiotic use, recent hospitalization, or augmentation of steroid dosage. Of the early CDC+ patients, 100% developed BOS, but only 52% of the late CDC+ patients developed BOS, either preceding or following infection.
Conclusion. CDC developed in 7.4% of lung transplant patients with identified risk factors, yielding a cumulative incidence of 14.7%. The statistical association of BOS development in early CDC+ patients suggests a relationship between early infections and future chronic lung rejection.     

Changing Trends in Surgery for Benign Gallbladder Disease

Hospital charts and notes of 2181 consecutive cholecystectomies performed between 1969 and 1984 were computer analyzed. They were divided into three categories of patients operated on 5, 10, and 15 yr ago. The trends of change throughout this period were as follows: 1) The population operated on in the last 5 yr is older, the proportion of males, especially over 70-80 yr old, and diabetics, is growing constantly. 2) The frequency of acalculous cholecystitis and gangrenous changes increase; the same is true for common bile duct pathology and positive bile cultures. 3) There is a marked decrease in hospitalization time, postoperatively, without significant increase in rate of wound infection and thromboembolic phenomena, or mortality. It seems that there is no change in the frequency of gallstone-related pancreatitis and perforations of gallbladder. The same is disappointingly true for positive choledochal exploration index. We think that the subcostal approach, with rational prophylactic and therapeutic antibiotic regimen, contribute to the shortening of hospitalization time and the fixed rates of wound infection and herniae in scar. Prophylactic heparin given subcutaneously seems to avoid possible thromboembolic phenomena.     

A single dose of ceftriaxone administered 30 minutes before percutaneous endoscopic gastrostomy significantly reduces local and systemic infective complications

OBJECTIVE: The aim of this study was to determine the efficacy of antibiotic prophylaxis in percutaneous endoscopic gastrostomy (PEG). METHODS: An open prospective, randomised, multicenter study was conducted in 141 patients; 72 received ceftriaxone 1 g i.v. 30 min preintervention, and 69 received no study medication. A standardized protocol was followed for PEG preparation, insertion, and aftercare; all patients received a 15-Fr gastrostomy tube. Follow-up of local and systemic infection and clinical course was continued to postintervention day 10. An aggregate erythema and exudation score >3 or the presence of pus was taken as indicative of peristomal infection. The pharmacoeconomics of antibiotic use were also examined. RESULTS: In no-prophylaxis patients, wound infection rates were 25% on day 4 and 26.4% on day 10, versus 10.1% (p = 0.03) and 14.5% (p = 0.10), respectively, in prophylaxis patients. Results were disproportionally better in tumor patients: systemic infection rates were 16.7% versus 5.8% in no-prophylaxis versus prophylaxis patients (p = 0.045), and overall infection rates 38.9% versus 17.4%, respectively (p = 0.046). Pneumonia was more frequent in patients with underlying neurological disease. Antibiotic costs were the same in both groups (p = 0.792). CONCLUSIONS: Single dose ceftriaxone 1 g is an effective prophylaxis against local and systemic infection after PEG.     

Cutaneous vasculitis associated with fluoroquinolones

Cutaneous vasculitis is a clinical entity with a broad differential diagnosis, including an adverse drug reaction. It is defined as inflammation of skin blood vessel walls. During a 7-year-period, we observed three patients who developed isolated cutaneous vasculitis during antibiotic therapy of bacterial infection. All were treated with a fluoroquinolone (ciprofloxacin or levofloxacin) combined with rifampin (two cases) or flucloxacillin (three cases), respectively. In all three cases the lesions gradually resolved after treatment with the inciting fluoroquinolone had been stopped. In one patient, leukocytoclastic small-vessel vasculitis was histologically confirmed. Fluoroquinolone-associated cutaneous vasculitis consists of an isolated self-limiting disorder that is part of a systemic vasculitis, or even life-threatening disease. Clinicians should be aware of this serious adverse event because any continuation of treatment may be fatal.     

Capnocytophaga species: infections in nonimmunocompromised and immunocompromised hosts

Retrospective review of isolates of Capnocytophaga, a genus of capnophilic gram-negative bacilli, referred to the Massachusetts State Laboratory Institute in Boston revealed 31 patients with infection due to Capnocytophaga, 16 in nonimmunocompromised hosts. These infections included empyema (three patients), lung abscess (one), sinusitis (one), conjunctivitis (three), subphrenic abscess (one), wound (three), osteomyelitis (one), and bacteremia (three). Two of the wound infections were closed-fist injuries involving bone or soft tissue. Capnocytophaga was frequently isolated as part of a polymicrobial infection with other oral flora. There was only one death in the nonimmunocompromised group. In contrast, of 15 immunocompromised patients with 16 episodes of bacteremia due to Capnocytophaga, 87% had leukopenia and 73% had significant oral pathology such as gingivitis, mucositis, or ulceration. Five immunocompromised patients died. Thus, Capnocytophaga species may cause disease in both nonimmunocompromised and immunocompromised hosts. Isolation of this organism should suggest an oral source for infection.     

Antibiotic prophylaxis in percutaneous endoscopic gastrostomy (PEG)--results from a prospective randomized multicenter trial

OBJECTIVE: To determine the efficacy of antibiotic prophylaxis in percutaneous endoscopic gastrostomy (PEG) as a part of a standardized regimen. METHODS: An open prospective randomised multicenter study in 216 patients. 106 received ceftriaxone 1 g i.v. 30 min preinterventionally and 110 no study medication. A standardized protocol was followed for PEG preparation, insertion, and aftercare; all patients received a 15 French gastrostomy tube. Follow-up of local and systemic infection and clinical course was continued to postintervention day 10. An aggregate erythema and exudation score > 3 or the presence of pus was taken as indicative of peristomal infection. The pharmacoeconomics of antibiotic use were also examined. RESULTS: In no-prophylaxis patients, wound infection rates were 23.6% on day 4 and 24.5% on day 10 vs. 7.6% (p < 0.05) and 11.4% (p < 0.05), respectively, in prophylaxis patients. Results were disproportionally better in tumor patients in comparison with neurological patients. Patients systemic infection rates were 11.8% vs. 1.9% in noprophylaxis vs. prophylaxis (p < 0.05), and overall infection rates 36.3% vs. 13.3%, respectively (p < 0.05). Pneumonia was more frequent in patients with underlying neurological disease and reduced in the prophylaxis group. Antibiotic and application costs were similar in both groups (p = 0.400). CONCLUSIONS: Single-dose ceftriaxone 1 g is a effective prophylaxis against local and systemic infection after PEG and should be a part of a standard regimen.     

Vibrio vulnificus infection

We report 3 cases of Vibrio vulnificus infections from Taiwan. Patient 1, who manifested symptoms of primary septicemia, died after 2 days. Patient 2, who had a wound infection and signs and symptoms of sepsis but negative blood cultures, responded to tobramycin and chloramphenicol plus surgical debridement, and recovered after 26 days of hospitalization. Patient 3 had secondary septicemia originating from a wound inflicted by a shrimp. Originally, the patient seemed to respond to ceftazidime and amikacin treatment along with surgical debridement, but subsequently died from adult respiratory distress syndrome (ARDS) induced by several episodes of aspiration which occurred after initial clinical improvements. We conclude that, for patients with severe wounds and evidence of V. vulnificus infection, an appropriate, powerful antibiotic, such as one of the third generation cephalosporins should be used as initial therapy unless the nature of the infection indicates other treatment.     

Clinical impact of infections caused by ESBL-producing E. coli and K. pneumoniae

The outcome of infections occurring at different anatomic sites caused by ESBL-producing E. coli or K. pneumoniae was retrospectively analysed for a 3-y period. 23 cases were compared to 46 controls with infections caused by third-generation cephalosporin-susceptible strains matched by age, severity of illness and duration of hospitalization before onset of infection. Only 27.8% of cases received appropriate empirical antimicrobial therapy compared with 79.6% of controls (OR(paired)=0.053, p=0.001). This did not result in higher costs of antibiotic therapy, a longer median post-infection hospital stay or higher mortality in cases of patients with urinary tract or wound infections. In cases of patients with respiratory tract and bloodstream infections (RTI/BSI), median costs of definitive antibiotic treatment were significantly higher than in controls (325 vs 58.9 Euros, p=0.002). Moreover, more case patients with RTI/BSI had a post-infection stay exceeding the 75th percentile of 15 d on ICU and of 18 d in hospital, respectively (50% vs 6.67%, p=0.034). There was no difference in in-hospital mortality between case and control patients with RTI/BSI (25% vs 20%, p=1.0).     

Can septicemia and ascitic fluid infections in cirrhotic patients be treated by the oral route alone?

The aim of this study was to determine the efficacy of oral antibiotics in the treatment of severe infections in cirrhosis. Twenty-two patients (17 males, 5 females) with spontaneous bacteremia (n = 7) or bacterial peritonitis (n = 15) were treated with oral pefloxacin 400 mg per 24 hr alone (n = 1) or in combination with another oral antibiotic, trimethoprimsulfamethoxazole (n = 13), amoxicillin (n = 6), cefadroxil (n = 2), or metronidazole (n = 1). In patients with spontaneous bacteremia, all organisms were found to be sensitive to oral antibiotics, and a favorable response was elicited in 6 out of 7 (86 p. cent) within 3 days (mean) of treatment. In patients with spontaneous peritonitis, ascitic fluid cultures were positive in 11 cases, and organisms were sensitive to pefloxacin in 9 out of 11 cases. A favorable response was elicited in 13 out of 15 within 2 to 8 days of treatment. Fourteen patients died (64 p. cent), 3 of infection (bacteremia n = 1, peritonitis n = 2), and 11 patients of causes unrelated to infection, mainly variceal hemorrhage, hepatorenal syndrome or hepatocellular carcinoma, although the clinical symptoms of infection were controlled. One-year survival was 57 p. cent in patients with bacteremia and 33 p. cent in those with bacterial peritonitis. Oral treatment was well tolerated in all patients. We suggest that most bacteremia and spontaneous bacterial peritonitis in cirrhotic patients can be treated with oral antibiotics. In some patients, this may be accomplished on an out patient basis.     

Are prophylactic oral antibiotics indicated for the treatment of intraoral wounds?

Patients with intraoral and oral-cutaneous wounds commonly present to emergency departments (EDs), usually after sustaining blunt facial trauma. Many of these wounds are minor, small (<1 cm), hemostatic on presentation, and confined to the oral mucosa, requiring no specific intervention. Some of these injuries, however, do require wound repair, in particular large mucosal wounds (1 to 2 cm) and those that communicate with the overlying facial skin ("through-and-through" wounds). Most emergency medicine textbooks consider these larger wounds to be at significant risk for infection because of oral bacterial flora and thus recommend that a course of prophylactic antibiotics be prescribed when primary repair of these wounds is performed in the ED, in addition to routine oral and local wound care. However, studies have shown that other wounds commonly considered to be at significant risk for secondary infection, such as simple lacerations of the hand, do not appear to conclusively benefit from prophylactic antibiotic therapy when careful wound preparation is performed before primary repair. We therefore reviewed the available literature to determine the strength of evidence supporting the use of prophylactic oral antibiotics for intraoral wounds treated and repaired in the ED.     

Effect of locally applied GM-CSF on oral mucositis after stem cell transplantation: a prospective placebo-controlled double-blind study

Oral mucositis is a frequent side effect of myeloablative chemo- and radiotherapy preceding stem cell transplantation. It causes pain, poor food intake, and is a port of entry for infection. We studied whether GM-CSF applied topically in the oral cavity can prevent or ameliorate this mucositis. In 36 consecutive patients undergoing a stem cell transplantation, we performed a double-blind placebo-controlled study of 300 micrograms GM-CSF in a 2% methylcellulose gel daily versus a 2% methylcellulose gel alone. Both were locally applied in the oral cavity. The primary end-point was mucositis as measured by the WHO toxicity scale for mucositis, oral assessment scale, and a subjective pain scale, all scored daily. The secondary end-points were need to give parenteral nutrition and morphine, incidence of fever and infections, and duration of neutropenia and hospitalization. No differences were found in the median subjective pain scores, WHO scores, and oral assessment scores between the placebo and the GM-CSF groups. In both groups, nine patients required morphine for pain control. Ten patients in the placebo group and 11 in the GM-CSF group received parenteral nutrition. Documented infections, use of broad-spectrum antibiotics, and number of days with fever were similar in the placebo and the GM-CSF groups. The duration of neutropenia below 0.5 x 10(9)/l (median 14.5 days in the placebo group versus 17 days in the GM-CSF group) and the duration of hospitalization (28.5 versus 29 days) was also not significantly different. We found no beneficial effect of 300 micrograms GM-CSF dissolved in a 2% methylcellulose gel applied locally for chemo- and radiotherapy-induced mucositis in patients undergoing a stem cell transplantation.     

Maintenance treatment with antibiotics in cystic fibrosis patients sense or nonsense?

The majority of patients with cystic fibrosis (CF) have chronic lung infection with a variety of organisms. It is accepted clinical practice to treat acute exacerbations of infection with appropriate oral or intravenous antibiotics. The aim of this paper is to review the use of maintenance antibiotics for these patients with chronic pulmonary infection. There is clinical trial evidence to support the use of maintenance treatment for patients chronically infected withStaphylococcus aureus orPseudomonas aeruginosa. No such evidence is available in the case ofHaemophilus influenzae orBurkholderia cepacia. Chronic infection withStaphylococcus aureus is commonly treated with maintenance oral flucloxacillin and chronic infection withPseudomonas aeruginosa either with 3-monthly intravenous antibiotics or long-term aerosol antibiotics. Further clinical trials need to be performed on many aspects of maintenance treatment for CF patients with chronic pulmonary infection.