Heterozygous beta thalassemia with an intermediate severity : (a report of 11 cases).
Antibiotic treatment of gynaecologic infections is beset with many problems, among which bacterial resistance to the antibiotics is a major one. This paper describes our experience with parenteral gentamicin in treating moderate, serious and life threatening gynaecologic infections caused by aerobic gram-negative bacilli and staphylococci.
One hundred and twelve patients admitted to the K.E.M. Hospital, Bombay, for various gynaecological and obstetrical infections, were studied [Table 1]. During treatment, patients were closely monitored by clinical and bacteriological response to therapy and for any possible adverse reactions, particularly ototoxicity or nephrotoxicity. The usual ancillary therapeutic measures, such as intravenous fluids to maintain fluid and electrolyte balance, corticosteroids as and when necessary and surgical intervention were also carried out. Eleven cases of incomplete septic abortions had blunt curettages for completion of abortions under antibiotic cover. Laparotomy and hysterectomy were undertaken in 17 cases which did not respond to conservative treatment or showed signs and symptoms of rupture of tubo-ovarian abscess. Colpopuncture and drainage of pus were done for 3 cases with pelvic abscess. Salpingooophorectomy was carried out in 5 cases. Peritoneal drainage was required in 3 cases. Emergency LSCS was required for amnionitis in one case.
Appropriate specimens for bacteriological studies (smears and swabs from wounds) were obtained before and after therapy in every patient. The therapy was started immediately after collection of the specimen without waiting for the bacteriological report. Laboratory investigations covering haematology and urine examination were carried out in all cases. BUN, creatinine, total and direct bilirubin, SGOT and SGPT estimations were done to assess the renal and liver functions. Eighth cranial nerve function was studied by audiometry and clinical examination for vestibular function, before, during and after therapy. Radiologic studies were carried out as necessary to rule out the presence of gas under the diaphragm in suspected cases of perforation of the uterus or the bowel. In moderate to severe infections, gentamicin was given intramuscularly in the dose of 3 mg/ kg/day in three equally divided doses. Patients with life threatening infections received 5 mg/ kg/day in three or four equally divided doses initially followed by 3 mg/kg/day. In patients with impaired renal function, the single dose of gentamicin of 1 mg/kg/ day was given, but the interval between the doses was extended. In some cases with severe infections caused by more than one organism, additional antibiotic therapy was resorted to, based on bacteriologic findings. Thus, ten patients received ampicillin in addition to gentamicin. As this drug is active against some anaerobic organisms, some of the cases could have been treated for anaerobic sepsis though a conscious search for anaerobic organism and specific treatment such as metronidazole was not given.
The clinical data is given in [Table 1]. The bacteriological data is summarised in [Table 2]. E. coli was the most common pathogen encountered. The other important pathogens were Klebsiella, coagulasepositive Staphylococcus, Pseudomonas and Proteus. The maximum types of isolates were obtained in patients with septic abortion with or without peritonitis. All the isolated strains were sensitive to gentamicin as tested in vitro by the Kirby Bauer method (Bauer et al). The types of antibiotics received by the various categories of patients before hospitalisation are given in [Table 3]. The majority had received broad spectrum antibiotic coverage with penicillin-streptomycin, tetracycline or chloramphenicol. [Table 4] summarises the outcome of gentamicin therapy in the one hundred and twelve crises treated. Surgical intervention was required in 40 patients.
Twenty out of 112 patients expired despite intensive therapy. These included ten with septic abortion, three with puerperal sepsis, four with post-operative infections, two with tubo-ovarian masses and one with pelvic infection. Some of these patients had complicating conditions such as endotoxic shock, peritonitis and septicaemia. Malignant ovarian tumour with pyosalpinx, choriocarcinoma with secondaries in the lungs and brain, puerperal tetanus and perforated uterus were found in one patient each.
Efforts were made to follow the patients through laparoscopy. In all, 27 laparoscopies were performed, which included 18 patients with history of septic abortion and 9 with tubo-ovarian masses and pelvic infections. Out of the 18 with septic abortion, one or both tubes were found patent in 16. Eight patients had intraperitoneal adhesions. Tubes were found blocked in all cases with tubo-ovarian masses or pelvic infections.
Laboratory assessment of adverse reactions with gentamicin therapy
Oliguria, jaundice, tingling and numbness of extremities, skin rash, puffiness of face or anaemia occurred in seven patients either singly or in combination. A rise of at least 0.4 mg% in serum creatinine levels was noted in 15 patients. It is not definitely known whether these changes were due to gentamicin therapy per se, or whether they could be attributed to the underlying disease processes, particularly endotoxic shock or septicemia. The occurrence of these side effects had no correlation with the dose of gentamicin or the duration of therapy.
Audiometry was performed in 55 patients, before, during and after therapy, Out of these, two patients were found to have diminished hearing at the end of therapy: both had received streptomycin prior to admission.
In vitro all bacterial isolates obtained from the patients were found to be sensitive to gentamicin as tested by the Kirby Bauer method. However, clinically, seventy-eight out of 112 cases experienced complete or near complete clearance of lesions. It is very likely that patients who did not respond to gentamicin inspite of in vivo sensitive bacteria were also infected by anaerobic organisms. Further, a complete resolution of inflmmation is extremely difficult to achieve in gynaecologic practice because of the high incidence of fibrotic sequelae, such as thickening of tubes, pelvic adhesions, etc. leading to complications like hydrosalpinx, inspite of complete eradication of bacteria. Moreover, some patients may harbour pockets of residual infection surrounded by fibrotic walls which prevent adequate penetration of the antibiotic to the actual tissue sites.
In this study, E. coli has emerged as the most common pathogen in gynaecologic infections. However, other pathogens such as coagulase-positive Staphylococci, Pseudomonas, Klebsiella and Proteus are also shown to have been highly pathogenic., 
The present finding of low ototoxicity with gentamicin supports the earlier observation of Falco et al and by Jackson and Arcieri. The latter found the overall incidence of ototoxicity with gentamicin to be only about 2%. In the present series, it is about 1.8%. Even when ototoxicity does occur with gentamicin, it affects primarily the vestibular function in most cases, so that hearing remains essentially unaffected.
Gentamicin ordinarily need not be combined with any other antibiotic in order to manage gynaecologic infections with aerobic organisms. Occasional cases may require complementary therapy with other antibiotics. Thus 10 patients required additional treatment with ampicillin in this series. However, in such cases, a penicillin type of antibiotic should be given by a separate injection and not mixed with gentamicin in the same syringe or IN. fluid, since such prior mixing inactivates gentamicin. Combination of gentamicin with tetracycline or chloramphenicol may lead to a reduction in antimicrobial activity and, is, therefore, not recommended.
At times, surgical procedures are necessary to remove the focus of infection and collection of pus. Moreover, a laparotomy is necessary whenever there is suspicion of perforation of the uterus or the bowel. The presence of products of conception in the uterus calls for the evacuation of the uterus.
We thank Dr. C. K. Deshpande, Dean, K.E.M. Hospital and Seth G.S.M. College for his permission to report this series, and Dr. S. Srinivasan, Medical Director, M,/s. C. E. Fulford (India) Private Limited (affiliated to Schering Corporation, U.S.A.) for the generous supply of gentamicin for this study.
We also thank Dr. Rege and Dr. Karnik, Department of Otorhinolaryngology for helping us with audiometry studies, and Dr. (Mrs.) Kang and Dr. (Miss) J. T. Panjabi for their help.