by M. P. Vora.

St. George’s Hospital, Bombay.

Indian Journal Of Medical Sciences

Volume No- 4, Number 2 of February 1950.

Page no. 54 to 56.


The occurrence of a complete change in the bacterial flora, in the human body may be observed occasionally during the course of treatment with an antibiotic. In these circumstances, the pathogenic organisms sensitive to the antibiotic in use disappear, or become less in number, while the insensitive organisms may appear in large numbers and cause a new infection and its symptoms. For example, when using penicillin for an infection caused by a Gram-positive organism, one may encounter a secondary infection caused by a Gram negative bacillus. The reverse may be true when one happens to use streptomycin.


The mechanism by which a new infection develops is not clear, but may be due to some disturbance in the state of equilibrium of bacterial antagonism, which is supposed to be normally present. It is also possible that the removal of bacteria by means of a specific antibiotic allows insensitive organism to increase not only in number but also in virulence.


Though the incidence of new infections does not seem to be very high, the occurrence of superinfection in patients receiving penicillin treatment serves to emphasise the great need for frequent and careful bacteriologic examinations before, during, and after the course of treatment.



Mrs. S. P., Hindu, age 20, female, married; one child 7 months old.

This woman was admitted into the medical department, St. George’s Hospital, Bombay, on 16 th January 1949, for weakness, pallor, and anaemia of three months duration.


The family history, personal history, and past history revealed nothing of any importance. General examination revealed the following: conjunctivae pale, nails pale and spoonshaped. Circulatory system- haemic murmurs. Respiratory system – normal. Alimentary system- tongue smooth and pale; liver and spleen not palpable. Central nervous system normal. The urine and stool examination showed nothing abnormal. R.B.C. 2.04 millions per; Hb. Less than 20%; W.B.C. 5000 per; Diff. count- Polymorphs 63%, Lymphocytes 32%, Eosinophils 3%, Hyalines 2%.


She was prescribed Ferri et Amm. Citras mixture I oz. T.D.S. and Liver Extract 2cc. intramuscularly daily. On 11 th January she had a rise of temperature. She complained of chill, fever, cough and pain in the chest. Physical examination showed limitation of movement and suppressed breath sounds on the right side of the chest. She was X-rayed on the 12 th January and a dense homogenous shadow at the base of the right lung was reported. By the 13 th morning, crepitations at the base of the right lung could be heard and the diagnosis of lobar pneumonia became obvious. Sputum examination showed a large number of Gram-positive diplococci, morphologically similar to pneumococci. The patient was given Mist. Pneumonia oz. I, four times a day and 40,000 units of penicillin sodium G in aqueous solution intramuscularly, at 3 hours intervals, day and night, from the 13 th to 21st January. She received 2.56 mega units of penicillin.


She felt very much better and her temperature touched normal on 21st January. But in the evening she complained of severe pain and burning of the urethra while passing urine. A gynaecological examination revealed the following: Uterus anteverted and normal in size, cervix small and red; purulent discharge from the cervical canal, urethra inflamed, and a drop of pus could be milked out from it; vagina very pale, fornices clear. Cervical and urethral discharge- smears showed a large number of pus cells and Gram-negative mixed bacillary flora; no Gram-negative intra-or extra-cellular diplococci; no Trichomonas vaginalis.


Urine examination: Acid reaction, Sp. Gr. 1018, traces of albumen, 20 to 30 pus cells per field under the 1/6 objective lens, few red blood corpuscles, no cysts; no crystals, no casts, no gonococci.


It was assumed that this was a case of specific urethritis and the patient was again put on penicillin 50,000 units 4 hourly on the 27 th January. Injections were continued till the end of 29 th January. She noticed no relief of her symptoms in spite of her receiving additional 0.9 mega units of penicillin. On 30-1-1949, she was transferred to venereal ward for treatment.


She denied any history of similar trouble previously. A repeat examination showed that the cervix was red and inflamed; urethra showed signs of inflammation. Smear examinations showed pus cells and Gram-negative coccobacilli. No Gram-negative diplococci were detected. Her husband was contacted. He denied any history of venereal disease; careful examination failed to show evidence of genitor-urinary infection in him. The blood Wassermann reaction in both husband and wife was negative.


The case was diagnosed as acute urethritis of non-specific origin, due to small Gram-negative bacilli, and she was given an alkaline mixture 1 oz. four times a day vaginal douches and bladder lavage daily with warm potassium permanganate, solution 1 in 8000 strength, at 102 to 105 F. she continued to receive, as before, treatment for her anaemia. In a couple of days, the patient felt better, there was no pain or burning at micturition. On the 16 th February 1949, the patient was again examined; redness of cervix and urethra had completely disappeared, there was no visible purulent discharge and the smears taken showed occasional pus cells and no organisms. She was discharged the same evening, as her anaemic condition had also improved greatly under treatment.


This was a case of pneumococcal pneumonia treated with penicillin, in which there developed a new infection of the urethra and cervix by short Gram-negative bacilli, not susceptible to this antibiotic. A course of penicillin therapy resulted in improvement of the pneumonic condition of the patient but this was followed by the emergence of Gram-negative bacillary infection of the urogenital system, giving rise to the new symptoms and requiring a change of treatment. Administration of more penicillin had no effects on the symptoms; but, rapid clinical, bacteriological and symptomatic improvement was noticed with the institution of local lavage and administration of an alkaline mixture. Pain and burning at micturition were no more felt; the urethra and cervix looked normal in appearance and smears did not show any organisms.


It is regretted very much that in this case bacteriological cultural studies could not be undertaken for want of facilities.



Lipman, Coss and Boots described changes in the bacterial flora of the throat and the intestinal tract during prolonged oral penicillin therapy. Weinstein discusses the subject of new infections developing during the course of specific antibiotic therapy and reports five cases. Stanley describes five cases in which a severe systematic infection due to Bacillus pyocyaneus developed during the course of treatment with penicillin and further suggests that the use of this antibiotic may have enhanced the virulence of Bacillus pyocyaneus. Appelbaum and Leff have reported two cases of this type.


Hughes and Carpenter carried out a study of 216 cases, alleged to be cases of penicillin resistant gonorrhoea and showed that only I9(9%) were infected with gonococcus as judged by bacteriologic examination of films and cultures. The remaining II7 (91%) were cases of non-gonococcic urethritis, the dominating organism being the alpha streptococcus, staphylococcus, diphtheroids and unidentified small Gram-negative bacilli. One does not know what proportion of the remaining cases of non-gonococcic urethritis was due this phenomenon of superinfection during penicillin therapy for gonorrhoea, and what proportion was due to added secondary infection due to faulty local therapy. Study on these lines would be of additional interest.



A case of pneumonia in which, following penicillin therapy, there developed a new infection of the urethra due to small Gram-negative bacilli, is reported. It is stressed that frequent and careful bacteriological examinations, in all patients before, during and at the completion of treatment with antibiotics are essential in order to detect fresh infection, in the course of antibiotic therapy. But for timely bacteriological examination, this case would have passed as a case of penicillin resistant gonorrhoea.



(b) I. Mcd. 235, 101- 1946.



I thank Dr. A. K. PARDHY, Superintendent, St. George’s Hospital, Bombay, for permitting me to publish this case report and the staff of the hospital for their kind co-operation.