SULFONAMIDES The  sulfonamides  were  the  first  effective chemotherapeutic  agents  to  be  available  in  safe therapeutic dosage ranges. They were the main- stay of therapy of bacterial infections in humans before the introduction of the penicillins in 1941. All  the  sulfonamides  are  synthetically  produced and  contain  the  para-amino-benzene  sulfanila- mide  group.  The  spectrum  of  activity  for  all  the sulfonamides is similar and all are effective against both  gram-positive  and  gram-negative  organisms. They  are  primarily  bacteriostatic  and  act  as  an antimetabolite (competitor) to para-aminobenzoic acid  (PABA)  in  susceptible  organisms.  PABA  is required  in  the  formation  of  folic  acid. Excretion   of   the   sulfonamides   is   chiefly through  the  kidneys.  Some  of  the  sulfonamides are relatively insoluble in acidic or neutral solu- tions so there is some danger that a sulfonamide would  precipitate  out  of  solution  leading  to  crystal formation,   hematuria,   or   possibly   renal   shut- down.  Forcing  fluids  to  keep  the  urine  dilute  or administering alkaline solutions can help to pre- vent  precipitation  of  sulfonamides.  With  the  newer sulfonamides,  this  is  not  a  major  concern  since many  of  them  are  soluble  in  acidic  solutions. Although the sulfonamides have, for the most part, been replaced with other agents, there is still a significant demand in certain types of infection, most  notable  urinary  tract  infections,  such  as acute cystitis or prostatitis, and in cases of acute otitis media. The following lists some of the more common   sulfonamides. Sulfisoxazole (Gantrisin) ACTION AND USE.— This  systemic  sulfona- mide is bacteriostatic and is indicated in the treat- ment of urinary tract infections and acute otitis media. USUAL DOSE.—  2 to 4 g initially, then 1 to 2  g  four  times  daily  for  10  days.  The  patient should  be  advised  to  increase  fluid  intake. Trimethoprim and Sulfamethoxazole (Bactrim, Septra) ACTION  AND  USE.—  This is an antiinfec- tive combination used in the treatment of urinary tract infections and otitis media. Both drugs are effective antimetabolites but compete at different steps in the formation of PABA. In combination, they  are  more  effective  than  individually. USUAL DOSE.— Two  tablets  every  12  hours. The  patient  should  be  advised  to  increase  fluid intake. Sulfacetamide (Sulamyd) ACTION  AND  USE.—  Sulfacetamide  is  an ophthalmic  bacteriostatic  for  the  treatment  of conjunctivitis, corneal ulcer, and other superficial ocular  infections.  It  is  available  in  solutions  of various  strengths  and  in  an  ointment  form. Sulfacetamide   is   inactivated   by   the   para- aminobenzoic  acid  in  purulent  exudates. USUAL  DOSE.—  Solutions  of  1  to  2  drops three or four times daily depending on the severity of the infection. The ointment should be applied four  times  daily. Silver Sulfadiazine (Silvadene) ACTION AND USE.—  Silver sulfadiazine is a topical antimicrobial agent used in the treatment of   second-   and   third-degree   burns   to   prevent wound sepsis. [t is water soluble and easily washed off  the  skin. USUAL DOSE.—  Silver  sulfadiazine  is  avail- able in an emollient cream and should be initially applied to a burn wound twice daily in a sterile manner.   For   each   dressing   change,   the   burn wound  should  be  debrided  of  any  dead  or sloughing tissues and carefully cleaned to remove any  residual  purulent  exudate. PENICILLINS Penicillin is one of the most important of the antibiotics.   It   is   derived   from   a   number   of Penicilliumm  molds  commonly  found  on  breads and  fruit.  The  mechanisms  of  action  for  the penicillins is the inhibition of cell wall synthesis during  the  reproductive  phase  of  bacterial  growth. It  is  one  of  the  most  effective  and  least  toxic  of the  antimicrobial  agents. Benzylpenicillin  (Penicillin  G)  is  the  prototype form  for  all  the  penicillins.  It  is  highly  effective against many of the gram-positive cocci, and, to a lesser extent, the gram-negative cocci. Semisyn- thetic  preparations  have  been  produced  to  attempt to overcome some of the problems of the naturally occurring  penicillins,  i.e.,  instability  in  an  acid medium,  rapid  renal  excretion,  susceptibility  to penicillinase,  and  a  high  incidence  of  hypersen- sitivity. Significant differences among the agents 7-8