The Use of Noncarbapenem ß-Lactams for the Treatment of Extended-Spectrum ß-Lactamase Infections.

The continued rise in infections caused by extended-spectrum ß-lactamase (ESBL)-producing pathogens is recognized globally as one of the most pressing concerns facing the healthcare community. Carbapenems are widely regarded as the antibiotics of choice for the treatment of ESBL-producing infections, even when in vitro activity to other ß-lactams has been demonstrated. However, indiscriminant carbapenem use is not without consequence, and carbapenem overuse has contributed to the emergence of carbapenem-resistant Enterobacteriaceae. The use of non-carbapenem ß-lactams for the treatment of ESBL infections has yielded conflicting results. In this review, we discuss the available data for the use of cephamycins, cefepime, piperacillin-tazobactam, ceftolozane-tazobactam, and ceftazidime-avibactam for the treatment of ESBL infections.

Correlation between cephamycin consumption and the incidence of antimicrobial resistance in Acinetobacter baumannii at a university hospital in China from 2001 to 2009.

OBJECTIVES: To investigate the correlation between cephamycin consumption and the prevalence of antimicrobial resistance in Acinetobacter baumannii. METHODS: Cephamycins consumption was expressed as defined daily dose (DDD) per 1,000 patient days by World Health Organization (WHO) Anatomical Therapeutic Chemical (ATC) classification index from 2001 to 2009. The incidences of antimicrobial resistance in A. baumannii were calculated using WHONET 5.4 software in the Microbiology Department. Correlation coefficient was used for statistical analysis. RESULTS: The results showed that cefmetazole and total cephamycin consumption (i.e., cefmetazole, cefoxitin, cefminox) both positively correlated with the percentages of A. baumannii resistance to piperacillin/tazobactam, ceftazidime, cefepime, imipenem/cilastatin, amikacin, levofloxacin, meropenem, respectively, these antimicrobial agents involved beta-lactams, carbapenems, aminoglycosides and fluroquinolones. In addition, the A. baumannii resistance rates of piperacillin/tazobactam, ceftazidime, cefepime, imipenem/cilastatin, meropenem, amikacin, levofloxacin were associated with the A. baumannii resistance rates of a number of antimicrobial drugs. This finding indicated the possible cross-resistances in four different classes of antimicrobial drugs. It could be due to multidrug resistance in A. baumannii. CONCLUSIONS: The cephamycin consumption was significantly related to the prevalence of the antimicrobial drug resistance and might be correlated with multidrug resistance in A. baumannii. Hence, the prescription of cephamycin should be reduced and optimized in order to avoid the rapid increase of antimicrobial resistance in A. baumannii.

Significance of SIRS score in therapeutic strategy for acute appendicitis.

BACKGROUND/AIMS: The surgical indication for acute appendicitis has been discussed diversely. SIRS (systematic inflammatory response syndrome) is a concept that has been advocated as the clinical criteria on inflammatory diseases. The aim of the current study was to elucidate the significance of SIRS score in deciding therapeutic strategies for acute appendicitis. METHODOLOGY: One hundred and twenty-five patients who were admitted with the diagnosis of acute appendicitis were investigated in the current study. The ultimate surgical indication was decided by the physical examination done by the surgeons. Fifty-nine patients were indicated for appendectomy. The relationship between decision for the surgical treatment for acute appendicitis and SIRS score/positive status was investigated. RESULTS: SIRS score of the patients who were treated with appendectomy was significantly higher than that of the patients treated with conservative therapy containing starvation and administration of antibiotics therapy and SIRS positive status in patients treated with appendectomy was also higher than that in patients with conservative therapy. CONCLUSIONS: SIRS score is also useful as objective and auxiliary information to determine the surgical indication for acute appendicitis.

Effectiveness of inpatient and outpatient treatment strategies for women with pelvic inflammatory disease: results from the Pelvic Inflammatory Disease Evaluation and Clinical Health (PEACH) Randomized Trial.

OBJECTIVE: Pelvic inflammatory disease (PID) is a common and morbid intraperitoneal infection. Although most women with pelvic inflammatory disease are treated as outpatients, the effectiveness of this strategy remains unproven. STUDY DESIGN: We enrolled 831 women with clinical signs and symptoms of mild-to-moderate pelvic inflammatory disease into a multicenter randomized clinical trial of inpatient treatment initiated by intravenous cefoxitin and doxycycline versus outpatient treatment that consisted of a single intramuscular injection of cefoxitin and oral doxycycline. Long-term outcomes were pregnancy rate, time to pregnancy, recurrence of pelvic inflammatory disease, chronic pelvic pain, and ectopic pregnancy. RESULTS: Short-term clinical and microbiologic improvement were similar between women randomized to the inpatient and outpatient groups. After a mean follow-up period of 35 months, pregnancy rates were nearly equal (42.0% for outpatients and 41.7% for inpatients). There were also no statistically significant differences between outpatient and inpatient groups in the outcome of time to pregnancy or in the proportion of women with pelvic inflammatory disease recurrence, chronic pelvic pain, or ectopic pregnancy. CONCLUSION: Among women with mild-to-moderate pelvic inflammatory disease, there was no difference in reproductive outcomes between women randomized to inpatient treatment and those randomized to outpatient treatment.

Possible asymptomatic carrier of salmonella typhimurium in the preputium: a case report.

Salmonella infections lead to several clinical syndromes such as acute gastroenteritis and bacteremia. Less frequent manifestations are extraintestinal focal infections, including urinary tract infections. A 10-month-old boy was admitted to the hospital with recurrent urinary tract infections treated with antibiotics. Salmonella typhimurium was isolated from the urine samples obtained in urine bags. The organism was also grown from a suprapreputial swab, but was not grown in the suprapubic urine specimen. Renal ultrasonography, intravenous pyelography and voiding cystourethrogram were found normal. The patient was then circumcised, following with no uropathogens were isolated from the urine. It is believed that circumcision not only prevented further urinary tract infection and protected the case from becoming a carrier of Salmonella typhimurium, it also halted a possible spread of Salmonella infection to the general public.

A randomised controlled trial of antibiotic prophylaxis in elective caesarean delivery.

OBJECTIVE: To determine whether prophylactic antibiotic administration using cefoxitin at the time of elective caesarean section significantly reduces infectious morbidity. SETTING: A tertiary teaching hospital in a large urban city in South Africa. PARTICIPANTS: Women undergoing elective caesarean section. DESIGN: A prospective, double-blind randomised placebo-controlled trial. METHODS: Four hundred and eighty women undergoing elective caesarean section had cefoxitin or placebo administration after umbilical cord clamping. Postpartum complications including febrile morbidity, wound infection, endometritis, urinary tract infection, pneumonia and transient postpartum fever were recorded, as were the duration of hospital stay and the need for therapeutic antibiotics. RESULTS: Wound infection was the most common complication occurring in 13.3% and 12.5% of women in the placebo and cefoxitin groups, respectively. Prophylactic antibiotics did not decrease febrile morbidity, wound infection, endometritis, urinary tract infection and pneumonia. Women who received cefoxitin stayed on average a day less in hospital than those who received placebo (6.9 vs 7.8 days, risk difference 0.94 CI 1.57 - 0.31 days). Eleven women (4.6%) in the placebo group and eight (3.4%) in the cefoxitin group had microbiological evidence of wound infection. Staphylococcus aureus was the most common pathogen (43%) isolated. Similar proportions in both groups (6.3% placebo and 5.1% cefoxitin) required a course of therapeutic antibiotics. CONCLUSION: Antibiotic prophylaxis with cefoxitin in elective caesarean section did not reduce post-operative infectious morbidity in this double-blind randomised placebo controlled trial.

Incidence of beta-lactamase production and antimicrobial susceptibility of anaerobic gram-negative rods isolated from pus specimens of orofacial odontogenic infections.

The incidence of beta-lactamase production in anaerobic gram-negative rods isolated from 93 pus specimens of orofacial odontogenic infections and the antimicrobial susceptibility of these isolates against 11 antibiotics were determined. A total of 191 anaerobic gram-negative rods were isolated from the specimens. Beta-lactamase was detected in 35.6% of the black-pigmented Prevotella and 31.9% of the nonpigmented Prevotella. However, no strains among the other species isolated produced beta-lactamase. Ampicillin, cefazolin and cefotaxime showed decreased activity as regards beta-lactamase-positive Prevotella strains, whereas the activity of ampicillin/sulbactam, cefmetazole, and imipenem continued to be effective against such strains. All tested beta-lactam antibiotics were effective against Porphyromonas and Fusobacterium. Erythromycin showed decreased activity against nonpigmented Prevotella and Fusobacterium. Clindamycin, minocycline and metronidazole were powerful antibiotics against which anaerobic gram-negative rods could be tested. The present study showed that beta-lactamase-positive strains were found more frequently in the Prevotella strains than in any of the other species of anaerobic gram-negative rods. The effectiveness of adding sulbactam to ampicillin was demonstrated, as well as the difference in cephalosporin activity against beta-lactamase-positive strains.

Extended-spectrum beta-lactamases. An overview.

The emergence of extended-spectrum beta-lactamase (ESBL)- producing Klebsiella pneumoniae and other ESBL-producing Enterobacteriaceae is an increasing problem and presents a dilemma for clinicians. The problem is not only detection of this resistance in the microbiology laboratory, but also a therapeutic dilemma due to multiple drug resistance to extended-spectrum beta-lactams and other agents, including fluoroquinolones, trimethoprim-sulfamethoxazole, and gentamicin. Currently, imipenem appears to be the drug of choice for serious infections due to these isolates, based on accumulating clinical experience. Because options for therapy are limited, control and prevention measures are particularly important. These should include not only traditional infection control measures such as contact precautions, but also antibiotic utilization measures, such as widespread empiric use of ceftazidime.

Cefminox versus metronidazole plus gentamicin intra-abdominal infections: a prospective randomized controlled clinical trial.

BACKGROUND: The aim of this prospective study was to compare the safety and efficacy of a new cephamycin, cefminox 2 g/12 h, to those of the usual regimen combining metronidazole 500 mg/8 h and gentamicin 80 mg/8 h (M+G). PATIENTS AND METHODS: 160 patients with clinically proven intra-abdominal infection were prospectively included in an open parallel randomized comparative multicenter trial. Antibiotics were started preoperatively and discontinued after clinical and laboratory evidence of resolution of the infection. Serum and peritoneal fluid levels and serum bactericidal activities were also studied. RESULTS: 150 patients were clinically evaluable. There was one failure in the cefminox group and three in the M+G group (not significant, RR: 1.07, 95% CI: 1-1.15). No differences were found in the number of wound infections, length of stay or duration of antibiotic therapy. Adverse effects were reported in 11 cases, all of them mild to moderate. Escherichia coli and Bacteroides fragilis were the most frequently found microorganisms. CONCLUSION: Cefminox is as effective and as safe as M+G in the treatment of intra-abdominal infections.

Ampicillin/sulbactam and cefoxitin in the treatment of cutaneous and other soft-tissue abscesses in patients with or without histories of injection drug abuse.

A randomized, double-blind trial compared the clinical and bacteriologic efficacy of ampicillin/sulbactam (2 g/1 g) and cefoxitin (2 g) administered intravenously every 6 h to patients with (n=49) or without (n=47) histories of injection drug abuse who presented with cutaneous or other soft-tissue infections. Cure or improvement occurred in 89.8% of ampicillin/sulbactam-treated patients, compared with 93.6% of cefoxitin-treated patients. The median time to resolution of all symptoms was 10.5 days with ampicillin/sulbactam treatment and 15.5 days with cefoxitin treatment. Mixed aerobic-anaerobic infection was encountered frequently in both treatment groups. A significantly higher percentage of Streptococcus species was found in the major abscesses of the patients with histories of injection drug abuse, compared with those without such histories (37% vs. 19%, respectively; P=.0009). Overall, ampicillin/sulbactam eradicated pathogens from the major abscesses in 100% of patients, whereas the eradication rate with cefoxitin was 97.9%. The 2 drugs were well tolerated. Ampicillin/sulbactam and cefoxitin were equally effective for the empirical treatment of cutaneous or other soft-tissue infections in injection drug abusers and patients who did not inject drugs.

Cefotetan-induced hemolysis associated with antibiotic prophylaxis for cesarean delivery.

We describe 3 cases of antibiotic-induced hemolysis associated with cefotetan prophylaxis during cesarean delivery. Each of the 3 patients showed development of significant anemia with documented cefotetan-induced hemolysis. When postpartum anemia is associated with antibiotic use, immune hemolytic anemia should be considered and included in the differential diagnosis.

Mycobacterium fortuitum osteomyelitis in a peripheral blood stem cell transplant recipient.

Mycobacterium fortuitum is an uncommon, but well-recognized, pathogen in immunocompromised hosts, with special predilection for bone and soft tissue infections in solid organ transplant recipients. We describe a case of osteomyelitis due to this pathogen in a peripheral blood stem cell transplant recipient.

Duration of antibiotic prophylaxis in high-risk patients with penetrating abdominal trauma: a prospective randomized trial.

To evaluate the effect of varying durations of antibiotic prophylaxis in trauma patients with multiple risk factors for postoperative septic complications, a prospective randomized trial was undertaken at an urban level I trauma center. The inclusion criteria were full-thickness colon injury and one of the following: (1) Penetrating Abdominal Trauma Index > 25, (2) transfusion of 6 units or more of packed red blood cells, or (3) more than 4 hours from injury to operation. Patients were randomly assigned to a short course (24 hours) or a long course (5 days) of antibiotic therapy. All patients received 2 g cefoxitin en route to the operating room and 2 g intravenously piggyback every 6 hours for a total of 1 day vs. 5 days. Sixty-three patients were equally divided into short-course (n = 31) and long-course (n = 32) therapy. This was a high-risk patient population, as assessed by the mean Penetrating Abdominal Trauma Index (33), number of patients with multiple blood transfusions (51 of 63; 81%), number of patients with an Injury Severity Score greater than 15 (37 of 63; 59%), number of patients with destructive colon wounds requiring resection (27 of 63; 43%), and number of patients requiring postoperative critical care (37 of 63; 59%). Differences in intra-abdominal (1-day, 19%; 5-days, 38%) and extra-abdominal (1-day, 45%; 5-days, 25%) infection rates did not achieve statistical significance. There continues to be no evidence that extending antibiotic prophylaxis beyond 24 hours is of benefit, even among the highest risk patients with penetrating abdominal trauma. A large, multi-institutional trial will be necessary to condemn this common practice with statistical validity.

Efficacy of liposomal antibiotic therapy in a rat infusion model of Escherichia coli peritonitis.

OBJECTIVE: To compare the potential therapeutic effect of liposomal vs. free cefoxitin. DESIGN: Randomized, controlled study, using a rat model of peritonitis. SETTING: Government research facility. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Rats were infused intraperitoneally with 6.5 x 10(8) colony forming units of Escherichia coli over 12 hrs. Animals were then randomized to receive intravenous saline, free cefoxitin, liposomal cefoxitin, or plain liposomes twice daily until they were killed. MEASUREMENTS AND MAIN RESULTS: Free cefoxitin significantly reduced the number of E. coli after 24 hrs compared with saline treatment in both liver and spleen. However, liposomal cefoxitin further decreased the bacterial content by five-fold to ten-fold in these organs. Minimal bactericidal effect was observed in animals injected with plain liposomes. Although administration of liposomal cefoxitin for 7 days further reduced bacterial counts in liver and spleen, there was no apparent beneficial bactericidal effect of free cefoxitin over saline at 7 days. There was approximately a ten-fold reduction in bacterial content in the lungs after 24 hrs in all three treatments, but no further reduction was observed after 7 days. There was no difference in 7-day survival rate in animals treated with plain liposomes or saline (45% vs. 39%). Although survival tended to increase with free cefoxitin treatment (64%), this outcome was significantly improved with the use of liposomal cefoxitin (82%). CONCLUSIONS: Liposomal cefoxitin enhanced bacterial killing in liver and spleen in this model of E. coli peritonitis. It also improved survival outcome relative to no treatment but not compared with free cefoxitin.

Prophylactic antibiotics for elective laparoscopic cholecystectomy: are they necessary?

HYPOTHESIS: Prophylactic antibiotic treatment in elective laparoscopic cholecystectomy does not lower the already low infection rate associated with this procedure. DESIGN AND SETTING: Prospective double-blind randomized trial at a community-based training hospital. PATIENTS: Four hundred fifty patients undergoing elective laparoscopic cholecystectomy were randomized into 1 of 3 treatment arms: (1) preoperative cefotetan disodium, 1g intravenously; (2) preoperative cefazolin, 1g intravenously; and (3) intravenous placebo. There were no demographic differences between groups in age, smoking history, American Society of Anesthesiologists score, infection risk class, time of antibiotic administration prior to surgery, and type of skin preparation. INTERVENTIONS: Laparoscopic cholecystectomy was attempted in all cases; however, 10 patients required conversion to an open cholecystectomy and they were included in the statistical analysis. Preoperatively, all patients were randomized in a blinded manner and received cefotetan, cefazolin, or placebo intravenously. RESULTS: There were 10 postoperative infections. In the cefotetan group, there were 3 cases of superficial surgical site infections. In the cefazolin group, there were 2 superficial surgical site infections-1 pneumonia and 1 rhinosinusitis. In the placebo group, there were 2 superficial surgical site infections and 1 urinary tract infection. The overall infection rate in this series was 2.4%. Follow-up was performed at routine postoperative visits and by telephone contact. Data were evaluated using the chi2 test and analysis of variance with Duncan post hoc test (P<.05). CONCLUSION: Based on our data, use of prophylactic antibiotics does not decrease the rate of wound infections in elective laparoscopic cholecystectomy.

Edwardsiella tarda bacteraemia--complicated by acute pancreatitis and pyomyoma.

Edwardsiella tarda (E. tarda) has recently become recognized as a pathogen in humans. Here we report a new case of E. tarda bacteraemia complicated by acute pancreatitis and pyomyoma. A 46-year-old female came to our emergency room complaining of sudden onset of left upper quadrant pain and vomiting for the previous few hours after drinking three bottles of wine. An abdominal computed tomography (CT) scan revealed multiple biliary stones, acute pancreatitis with extensive inflammatory change, and a large uterine myoma. Fever, watery diarrhoea, and mild suprapubic discomfort with vaginal spotting were noted soon after admission. The patient's blood cultures yielded E. tarda and symptoms subsided after antibiotic therapy. Fever and severe suprapubic pain with rebound tenderness developed 12 days later. Repeat abdominal CT scan revealed an enlarged uterine myoma with central necrosis. The patient subsequently underwent anterior total hysterectomy and bilateral salpingo-oophorectomy, revealing a uterine myoma with infarction and abscess formation. The patient recovered uneventfully and was discharged 1 week later.

[Should cefminox substitute cefoxitin in infections caused by bacteria susceptible to both drugs?]. / Debe sustituir cefminox a cefoxitinaen en las infecciones por bacterias sensibles a ambos?

We studied the in vitro activity of cefminox (MIC by agar dilution) and cefoxitin against 477 facultative Gram-positive and Gram-negative isolates which were recovered from clinical specimens and identified by standard methods. Cefminox has proved to be 4-16 times more active than cefoxitin against enteric Gram-negative bacilli commonly involved in cholecystitis, secondary peritonitis, intraabdominal abscesses and gynecological infections. On the contrary, cefoxitin has proved to be four times more active against Gram-positive cocci. Both have been ineffective against Enterobacter spp., Pseudomonas aeruginosa and Acinetobacter spp. The microbiological activity and pharmacokinetic parameters of cefminox make it one of the first choice treatments for community-acquired intraabdominal and pelvic infections with the presence of anaerobes.