Chemotherapy of experimental streptococcal endocarditis. I. Comparison of commonly recommended prophylactic regimens.

The effectiveness of various antibiotics commonly recommended for the prophylaxis of bacterial endocarditis has been evaluated in experimental streptococcal endocarditis in rabbits. High doses of penicillin G did not prevent the development of this infection. The only consistently successful prophylactic regimens using penicillin alone were those which provided for both an early high serum level and more than 9 h of effective antimicrobial action. Vancomycin was the only other drug which proved uniformly successful when given alone, even though the duration of its antimicrobial action in the blood was only 3 h. However, combined therapy using penicillin G or ampicillin with streptomycin was always effective in prophylaxis. Treatment with single injections of ampicillin, cephaloridine, cephalexin, clindamycin, cotrimoxazole, rifampicin, streptomycin, erythromycin, and tetracycline failed to prevent infection. The findings provide information on the effect of antimicrobials in vivo and may be applicable to the chemoprophylaxis of infective endocarditis in clinical practice.

Chemotherapy of experimental streptococcal endocarditis. II. Synergism between penicillin and streptomycin against penicillin-sensitive streptococci.

Bacterial endocarditis was produced by intravenous injection of Streptococcus viridans into rabbits with preexisting sterile endocardial vegetations. After 6 h had elapsed, bacteria in the vegetations could not be eradicated by brief treatment with antimicrobials to which the streptococci were sensitive. However, when treatment with penicillin was continued for 4 days, the animals were cured. The 6-h infection therefore offered a model in which treatments could be conveniently compared over a short period. Synergism was demonstrated between penicillin and streptomycin in endocarditis due to a fully penicillin-sensitive streptococcus, a point which had not been previously proved in vivo. The clinical implications are discussed.

Past and current roles for cephalosporin antibiotics in treatment of meningitis. Emphasis on use in gram-negative bacillary meningitis.

The therapy of gram-negative bacillary meningitis is less than adequate to date; the agents recommended do not achieve bactericidal levels in purulent cerebrospinal fluid. Because optimal antibiotic therapy of meningitis occurs when the cerebrospinal fluid level of an antibiotic is above the concentration needed to kill the offending pathogen, another group of agents needs to be considered. The newer cephalosporins or cehalosporin-type antibiotics (cefotaxime, moxalactam), by virtue of their marked activity against gram-negative bacilli and their ability to achieve significant CSF levels, merit serious consideration as therapy for gram-negative bacillary meningitis. Investigators in Europe and the United States have developed preliminary data demonstrating the efficacy of these agents in a growing number of cases. In the group presented herein, of the 35 cases in which gram-negative bacillary meningitis was treated with the newer cephalosporins, there were only four failures.

Antibacterial Drugs today: II.

Since the development of the sulphonamides in the 1930s and the subsequent development of antibiotics from the 1940s onwards, there have now been many drugs developed which are capable of chemotherapeutic activity in a patient infected by a susceptible micro-organism. This review is concerned with precise descriptions of important groups of antimicrobial drugs, with emphasis being placed on the more recently developed drugs. With each group of drugs the pharmacology, major therapeutic indications, dosages and adverse reactions are discussed. Part II of the review discusses the cephalosporins, polymyxins and aminoglycosides. The place of each in therapy is defined.

Intravitreal injection of cephaloridine in the treatment of endophthalmitis.

Ocular toxic effects of intravitreal injection of cephaloridine in rabbits was evaluated, and none were produced in doses of 0.25 mg or less. Clinically, intravitreal injection of cephaloridine in doses of 5 mg or more produced small punctate hemorrhages in the vascularized portions of the rabbit retina within two days. With doses of 2.5 mg or less, no clinical changes were seen during the two weeks of observation. Histologically, one day following intravitreal injection of 0.5 to 10 mg of cephaloridine there was clumping of the outer segments of the photoreceptors and destruction of the retinal pigment epithelium. Ten milligrams of cephaloridine intravitreally injected caused definite electroretinogram (ERG) changes ten minutes after injection. After 24 hours, the ERG was extinguished. An experimentally induced Escherichia coli endophthalmitis was successfully treated after six hours by intravitreal injection of cephaloridine.

Endophthalmitis caused by Moraxella nonliquefaciens.

We report the first case of endophthalmitis caused by Moraxella nonliquefaciens. Most likely, entry followed minor trauma from a contact lens, with the marked invasiveness of the organism resulting from the patient's immunocompromised state. This case, in addition, serves to illustrate the advantage of genetic transformation assay to differentiate the species of this group of organisms.

Gram-negative septicaemia during haemorrhage from an anastomotic ulcer.

Gram-negative septicaemia (Klebsiella) occurred on two occasions in a patient bleeding from an anastomotic ulcer. It is postulated that the presence of this organism in the gut of such a patient provided the portal of entry for this infection.

Serial nitroblue tetrazolium tests in the management of infection.

Two cases are described in which extensive use was made of the nitroblue tetrazolium (NBT) test. In the first case the advantages of using this technique to diagnose and control infection is shown; in the second the considerable advantage of the speed of the technique. In both of these cases the test made a material contribution to the management of the patient, and it is concluded that the test brings bacteriological control of the patient within the immediate clinical area, thus overcoming one of the principal disadvantages of the classical bacteriological methods.

Prophylactic antibiotics in colon surgery.

One hundred twenty-three patients undergoing elective colon surgery were prospectively and randomly assigned to receive either three 1-g perioperative doses of intramuscular cephaloridine or three 1-g preoperative doses of both oral erythromycin base and neomycin sulfate. All patients had their bowels thoroughly cleansed mechanically. The groups were comparable in age and nutritional status. Eight wound infections occurred in the 65 patients receiving cephaloridine (12.3%) v one in the 58 receiving erythromycin and neomycin (1.7%). The difference was statistically significant. Eight of nine infected patients had only wound infections; the majority of cultures yielded Bacteroides fragilis. Serum and tissue antimicrobial concentrations were determined in the first 70 randomized patients at operation. Mean (+/- SD) cephaloridine levels were 14.7 +/- 10.2 and 10.5 +/- 10.0 mg/L in serum and tissue, respectively, compared with 1.98 +/- 1.58 and 0.699 +/- 1.146 mg/L for serum and tissue erythromycin levels.

Factors that influence surgical wound infections. Role of prophylactic antibiotic therapy.

A comprehensive review of the factors responsible for postoperative wound sepsis is discussed, along with the experimental basis for the use of prophylatic antibiotics and a review of the results of the use of systemic and topical antibiotics on the incidence of surgical wound infections. Based on the data presented, suggestions are made which should minimize the development of postoperative wound infections.

Clinical value of sensitivity determinations in treating urinary tract infections.

The results of bacterial susceptibility testing in 2,413 urine specimens obtained from patients with urinary tract infections indicated that in a high percentage clinical response could be predicted without the need for antimicrobial sensitivity testing. Simply identifying the infecting organism will provide the clinician with enough information to treat most urinary tract infections intelligently. The relative effectiveness of antimicrobial agents to enable the proper selection of therapy in patients with urinary tract infections is discussed.

Further observations on the diagnosis cause, and treatment of endophthalmitis.

In our study of 54 suspected cases of endophthalmitis, vitreous aspiration was more sensitive in making a culture-proven diagnosis than anterior chamber paracentesis; Staphylococcus epidermidis was a more common cause of endophthalmitis than previously appreciated; and intraocular antibiotics in the recommended dosage are reasonably safe clinically and add a new dimension to the treatment of endophthalmitis.

Intra-incisional cephaloridine: a comparison of two methods of administration.

Serum cephaloridine concentrations were measured in the immediate post-operative period in 23 patients who had received a prophylactic dose of 1 g of the drug into the wound at the end of operation. Eleven patients received the antibiotic as a powder and 12 as a solution. The serum concentrations were higher, though not significantly so, in the group receiving powder, and this is thought to be due to the lesser amount of spillage and loss into dressings when the antibiotic is given in this form.

Latamoxef for the prophylaxis of abdominal surgical wound infection: a controlled clinical trial.

In a series of 236 abdominal operations, patients were allocated at random to receive a single intravenous dose of either 1 g cephaloridine or 1 g latamoxef (at induction of anesthesia) for the prophylaxis of postoperative wound infection. Of the 116 patients given latamoxef, one developed major and seven minor wound infections, whereas five major and 21 minor infections occurred in the cephaloridine group (P less than 0.01). Latamoxef has now replaced cephaloridine as our prophylactic antibiotic of choice in potentially contaminated abdominal operations.

Discriminate use of antibiotic prophylaxis in gastroduodenal surgery.

In a prospective study of 107 patients undergoing surgery for gastroduodenal disease, antibiotics were withheld from a group of 24 patients defined preoperatively to be at low risk of developing postoperative infections; no wound infection occurred in this group. Perioperative cephaloridine was randomized among the remaining patients (high risk). Wound infections developed in 11 of 42 patients who did not receive cephaloridine, but in none of the 41 patients who were given cephaloridine (p less than 0.02). Coliform bacteria were grown only from swabs of the stomach mucosa of patients in the high risk group and were the main cause of wound infections. Severe preoperative lymphocytopenia was frequently associated with the development of serious postoperative sepsis. The results validate a policy of restricting antibiotic prophylaxis in gastroduodenal operations to patients at high risk of postoperative infection and suggest a new risk factor--the preoperative blood lymphocyte count.

Therapy of staphylococcal infections: (a comparative study of cephaloridine and gentamicin).

Two groups of 38 patients have been treated for staphylococcal infection with either cephaloridine (4 gm daily) or gentamicin (320 mg daily) by the intramuscular route. The rate of favorable clinical response was higher among the patients who received cephaloridine (78.8 per cent) than among those who were treated with gentamicin (60.5 per cent). No death related to the infection occurred in the cephaloridine-treated patients. The mean peak and trough antibacterial activity reached in the serum of the patients after injection of the antibiotics was higher in patients receiving cephaloridine (1/64 and 1/16) than in those treated with gentamicin (1/16 and 1/4). Patients who failed to respond to therapy had often a low antibacterial activity of the serum. These studies suggest that the 1/8 level of bactericidal activity should be attained in the serum one hour after the administration of the antibiotics to allow optimal results in staphylococcal infections.

The enhancement of beta-lactam antibiotic therapy by novobiocin.

Novobiocin demonstrates an effect similar to that of probenecid (the "probenecid effect") in enhancing the therapeutic efficacy of antibiotics excreted mainly by the renal tubules. The ability of cefoxitin, cephalexin, cephalothin and penicillin G to protect mice against infection with Salmonella schottmuelleri was enhanced 2- to 3-fold when the animals were given oral doses of either probenecid or of novobiocin. The efficacy of cephaloridine, excreted mainly by glomerular filtration, was not enhanced by either probenecid or by novobiocin.

A controlled trial of intraperitoneal cephaloridine administration in peritonitis.

From a controlled therapeutic trial extending for more than 2 yr and involving 69 patients with appendicitis and peritonitis a clear-cut statistically significant result emerged. There was a major reduction in the incidence of intraperitoneal abscesses using cephaloridine by the intraperitoneal as opposed to the systemic route. After randomized selection into treatment and control groups, cephaloridine, 25 mg/kg was given by injection every 6 hr for 48 hr to the treatment group by i.p. installation and to the control group by systemic injection. Both groups received initial intraoperative peritoneal lavage with normal saline and also continued systemic injections of cephaloridine on postoperative days 3, 4, and 5. Only one out of 36 patients in the treatment group developed a residual intraperitoneal abscess, as opposed to six abscesses developing in 33 patients in the control group. Technical problems and complications of the method were trivial and have not prevented us from continuing and extending the applications of the method.

Prophylactic antibiotics for women undergoing vaginal hysterectomy.

A triple-blind prospective study of women undergoing vaginal hysterectomy was conducted to compare cefazolin, cephaloridine and no antibiotic, Both cefazolin and cephaloridine were given preoperatively, whereas only cephaloridine was given postoperatively. One gram of cefazolin given intramuscularly on call to the operation room was found to be a safe and effective antibiotic for prophylaxis against febrile morbidity. The proper utilization of prophylactic antibiotics seems to be in the immediate preoperative period. The use of antibiotics after the first day of surgery is unnecessary.

PIP: A triple-blind prospective study of 153 women undergoing vaginal hysterectomy between March 1974-February 1975 at Brooke Army Medical Center, was conducted to compare prophylactic antibiotic treatment with nontreatment. The antibiotics studied included cefazolin and cephaloridine. Treated patients received either 1 gm cefazolin on call to the operating room, 3 gm cephaloridine divided into 1 gm doses on call to the operating room, and 1 gm 12 hours later; or were untreated. Febrile morbidity occurred in 7.7% of patients on cefazolin, 12% on cephaloridine, and in 49% of the controls. The predominant organisms recovered were beta hemolytic Streptococcus, group D, intraoperatively and Escherichia coli, postoperatively. The effective use of preoperative prophylaxis is demonstrated.

[Case of bullous pneumopathy in an adult]. / Un caso di pneumopatia bollosa nell'adulto.

A case of bullous pneumopathy in an elderly subject is reported. The particular localization of the pneumonic process at the base of the left lung led to an initial suspicion of diaphragmatic relaxation. Subsequent development and the onset of pneumatoceles within the non-infiltrated pulmonary parenchyma led to a definite diagnosis of bullous pneumopathy which, from its clinico-radiological course, was attributed to a staphylococcic aetiology. Toxic-infective state with leucocytosis and polynucleosis; variability of radiological pictures; early pleural picture; sensitivity to Cephaloridine (which in the present case probably confined the condition to the left lung only); the benign course of the disease; all these elements pointed to staphylococcic bullous pneumopathy in the absence of any cultural demonstration. The different disease conditions in which pneumatoceles occur are reviewed along with the possible mechanisms for their formation.