Haragopal Thadepalli

Amniotic fluid analysis for antimicrobial factors

The antimicrobial factors in amniotic fluid (AF) were analyzed in 81 women during various periods of gestation. The AF inhibited the growth of E. coli 026 when the phosphate/zinc ratio was <200 or iron ≤1.2 μg/ml and unbound transferrin was >40%. A heatstable non‐lysozymal phosphate insensitive cationic protein with molecular weight higher than transferrin was also found in inhibitory AF. The antimicrobial properties of AF did not correlate with absolute zinc or lysozyme levels. The AF was non‐inhibitory when it contained >60 ± μg/ml of phosphate with phosphate/zinc ratio >200, iron >1.2 μg/ml and unbound transferrin was <40%. Amongst all criteria described, iron (P = 0.002) and unbound transferrin levels (P = 0.0005) were the most reliable and consistent all through pregnancy but others were highly reliable only during the 36th–40th week of gestation. The clinical application of these factors are being investigated.

In vitro activity and in vivo evaluation of ticarcillin plus clavulanic acid against aerobic and anaerobic bacteria

The efficacy of ticarcillin plus clavulanic acid was compared with that of certain broad-spectrum antibiotics such as ticarcillin, azlocillin, and piperacillin against blood culture isolates of aerobic bacteria obtained from seriously ill patients and anaerobic bacteria obtained from other miscellaneous infections. Ticarcillin plus clavulanic acid was found to be as effective as other broad-spectrum antibiotics against most of the 285 septicemic isolates tested. Ticarcillin plus clavulanic acid was most effective against 351 anaerobic bacteria, including B. fragilis. Further, 32 strains of B. fragilis that were relatively resistant to ticarcillin and azlocillin were tested with a mixture of ticarcillin or azlocillin, each in combination with clavulanic acid. Ticarcillin plus clavulanic acid inhibited all 32 strains of B. fragilis. Addition of clavulanic acid to cephalothin, penicillin, or azlocillin also augmented the antibiotic activity against B. fragilis by 4- to 64-fold. These in vitro data suggest that ticarcillin plus clavulanic acid may be used as a single antibiotic in the cases of bacterial septicemias and that the combination may be used in the treatment of multiple-antibiotic-resistant bacterial strains. In a related study, the augmentation activity of clavulanic acid with penicillin or ticarcillin was evaluated against B. fragilis in a rat intra-abdominal abscess model. Gelatin capsules filled with a mixture of B. fragilis and Escherichia coli were implanted intraperitoneally in male Wistar rats. Four different groups of animals with appropriate controls were treated with penicillin or ticarcillin alone or in combination with clavulanic acid. Treatment was started immediately or delayed for 48 hours after peritoneal soilage. The mortality rate decreased by almost one half when antibiotic therapy was started immediately. Treatment with ticarcillin plus clavulanic acid resulted in a cure in 70 to 89 percent of animals, showing that this combination is the most effective regimen in the treatment of rats with experimental intra-abdominal abscesses caused by B. fragilis and E. coli.

Cardiac tuberculosis: TB of the endocardium.

Tuberculosis involving the endocardium is extremely rare. The diagnosis is usually made during autopsy. Often there is involvement of other parts of the heart as well as other regions of the body. The infection is a result of direct extension from the myocardium or hematogenous spread. Two cases of disseminated tuberculosis with endocardial involvement are reported. In Case 1 miliary tuberculosis was diagnosed during life but the patient succumbed to extensive disease on the third hospital day. The patient in Case 2 presented with congestive cardiac failure and the possibility of tuberculosis was not suspected during life.

Ticarcillin plus clavulanic acid versus moxalactam in the treatment of skin and soft tissue infections

A formulation of 3.0 g of ticarcillin and 0.1 g of clavulanic acid was evaluated in the treatment of skin and soft tissue infections, and its efficacy was compared with that of moxalactam in a randomized open study. Thirty-three patients received 3.1 g of ticarcillin plus clavulanic acid every six hours via intravenous infusion, and 36 patients received 2.0 g of moxalactam every eight hours via intravenous infusion. Diagnostic categories included intramuscular abscesses, cellulitis, skin ulcers, gangrene, and perirectal abscesses. The average age of the patients and the duration of therapy were similar in both groups. Overall, 45 aerobic and 25 anaerobic bacteria were isolated from the ticarcillin plus clavulanic acid-treated patients; 58 aerobic and 24 anaerobic bacteria were isolated from the moxalactam-treated patients. Thirty of 33 patients in the ticarcillin plus clavulanic acid-treated group had a satisfactory response; a skin rash developed in one patient; therapy failed in one patient with Staphylococcus aureus infection; and one patient died as a result of a bleeding peptic ulcer. In the moxalactam-treated group, 32 of 36 patients had a satisfactory response; a skin rash developed in one patient; therapy failed in a patient with Pseudomonas aeruginosa infection; and two patients were unevaluable. Ticarcillin plus clavulanic acid as a single agent was found to be as effective as moxalactam in the treatment of skin and soft tissue infections.

Cyclic Changes in Cervical Microflora and Their Effect on Infections following Hysterectomy

In a prospective study the cyclic changes in the cervical microflora and the endometrial histology were correlated with the incidence of postoperative infections in 99 women undergoing elective abdominal hysterectomy. Escherichia coli and Bacteroides fragilis were isolated more frequently during the proliferative phase than during the secretory phase and, correspondingly, postoperative infections were more frequent when operated during the proliferative phase than during the secretory phase. Moderate to severe infections occurred in 31.6% of the patients operated during the proliferative phase in contrast to 18% during the secretory phase. This suggests increased host susceptibility to infection during the proliferative phase.

Anaerobic bacteria associated with cervical neoplasia

Abstract The possible association between cervical neoplasia and anaerobic bacteria was examined by correlating the histopathology of cervical biopsies with anaerobic cultures obtained from the cervix in 90 patients. Fourteen patients had invasive carcinoma of the cervix (ICC). All but one of them had Stage I or II disease. Severe dysplasia was present in 11 patients, moderate dysplasia in 9, mild dysplasia in 11, and carcinoma in situ in 26. Cultures from patients with ICC were characterized by a relative sparsity of anaerobes. The cultures of 3 of 14 patients with ICC contained anaerobes, in contrast to 53 of 76 patients in the other categories. Further, none of the 14 patients with ICC had anaerobic gram-negative bacilli whereas they were present in 18 of 76 patients in the other categories. ICC was not associated with any specific anaerobic bacteria. These data suggest that anaerobic bacteria are sparse and anaerolic gram-negative bacilli are rare in early invasive carcinoma of the cervix.

Clinical Evaluation of Piperacillin

28 patients with aerobic (7), anaerobic (7), and mixed (14) infections were treated with intravenous piperacillin for an average duration of 14 days. All bacterial isolates tested in this study were susceptible to piperacillin less than or equal to 128 micrograms/ml. 27 patients were treated with 20 g of piperacillin/day in four divided doses. 1 patient with renal failure received only 8 g/day. 26 patients were treated with piperacillin and two with Staphylococcus aureus infection received gentamicin in addition. The peak serum levels were 266 micrograms/ml at 1 h and the trough 16 micrograms/ml at 5 h. In all, 26 patients (93%) were cured, one had recurrence, and one failed. Adverse effects were pruitus in two patients, transient elevation of LDH in one, and transient eosinophilia in another. In our preliminary study, piperacillin was found to be safe and effective in the treatment of clinical infections.

Chemoprophylaxis of Anaerobic Pulmonary Infections

Chemoprophylaxis of anaerobic pulmonary infection due to aspiration was studied in a rabbit model with the view of comparing the efficacy of procaine penicillin, clindamycin, chloramphenicol, doxycycl

Antimicrobial activity and synergism of cefuroxime on anaerobic bacteria.

In vitro efficacy of cefuroxime was tested against 333 clinical isolates of anaerobic bacteria, including 80 strains of Bacteroides fragilis. Its activity was compared with that of cefamandole and cefoxitin. In addition, the antimicrobial synergism of cefuroxime was tested in combination with either penicillin or carbenicillin against B. fragilis. At 16 microgram/ml, cefuroxime inhibited 70% of all anaerobic bacteria, but it was ineffective against 64% of B. fragilis strains tested. Cefuroxime in combination with penicillin or carbenicillin exerted excellent synergistic activity against two of the three isolates of B. fragilis tested and had an additive effect on the other. Although cefuroxime by itself is ineffective against B. fragilis, it acts synergistically with penicillin or carbenicillin.

Susceptibility of intestinal anaerobes to new beta-lactam antibiotics.

In vitro susceptibility of 473 isolates of anaerobic bacteria derived from patients hospitalized for treatment of abdominal trauma was tested against third-generation cephalosporins--moxalactam, cefotaxime, ceftizoxime, cefmenoxime--and a penicillin--N-formimidoyl thienamycin--by serial agar dilution method in the anaerobic glove box. There were 208 Bacteroides isolates including 80 Bacteroides fragilis and 100 peptococci and peptostreptococci. The minimal inhibitory concentration (MIC) 75% of B. fragilis was less than or equal to 32 micrograms/ml for the cephalosporins tested and less than or equal to 8 micrograms/ml for thienamycin. The MIC of B. fragilis and Bacteroides vulgatus was not much influenced by increased inoculum size. Characteristically, peptostreptococci and peptococci were resistant to all four cephalosporins tested with MIC 75% being 32-64 micrograms/ml. All five antibiotics in this study appear suitable for therapy of intraabdominal suppurative infections, but the poor activity of third-generation cephalosporins on anaerobic cocci can be a cause of concern.