Letters to the Editor
I03
reports on the third day, therapy was changed to oral ampicillin for a further 5 days. A follow-up visit 3 months after discharge showed full recovery, with normal radiographic findings. T h e clinical presentation of this patient was unique because only soft tissues were affected without any restriction of movement or involvement of the bones and joints. T h e r e was no accompanying febrile illness or history of trauma. T h e patient made a complete clinical recovery and the peripheral W B C and E S R returned to normal within days of completing his antibiotic treatment. T h e significance of the isolate is confirmed by the patient's clinical picture, the isolation of the organism from several blood culture bottles and laboratory data indicative of acute inflammation. T h e commonest pathogens in the aetiology of arthritis and osteomyelitis in infants and young children remain Staphylococcus aureus, Haemophilus influenzae, Streptococcus pneumoniae and Streptococcus pyogenes. 3'4 It is possible that fastidious G r a m negative micro-organisms such as K. kingae play a larger role in the pathogenesis of arthritis and osteomyelitis than has previously been reported. 5 Kingella kingae has an affinity for skeletal tissues in infants and children, but the reasons for this are currently unknown. T h e prognosis for clinical recovery following treatment with penicillin is excellent.
*Departments of Orthopaedic Surgery and t Medical Microbiology, Altnagelvin Area Hospital, Londonderry B T47 I SB, Northern Ireland, U.K.
P. E. Chiquito* J. Elliott* S. S. Namnyakt$
:~ Author to whom correspondence should be addressed References
i. Gamble JG, Rinsky LA. Kingella kingae infection in healthy children. J Pediatr Orthop 1988; 8: 445-449. 2. de Groot R, Glover D, Clausen C, Smith AL, Wilson CB. Bone and joint infections caused by Kingella kingae: six cases and review of the literature. Rev Infect Dis 1988; IO: 998-1oo4. 3. Welkon CJ, Long SS, Fisher MC, Alburger PD. Pyogenic arthritis in infants and children : a review of 95 cases. Pediatr Infect Dis 1986; 5: 669-676. 4. Syriopoulou VP, Smith AL. Osteomyelitis and septic arthritis. In: Fegin RD, Cherry JD, eds. Pediatric infectious diseases. End ed. Philadelphia: WB Saunders, 1987: 759-779. 5. Verbruggen AM, Hauglustaine D, Schildermans F et al. Infections caused by Kingella kingae: a report of four cases and review. J Infect 1986; 13: 133-142.
C i p r o f l o x a c i n as a n e f f e c t i v e a n t i b a c t e r i a l a g e n t i n s e r r a t i a e n d o c a r d i t i s
Accepted for publication 3 July 199o Sir, Ciprofloxacin is a fluoroquinolone derivative with a high degree of tissue penetration and in vitro activity against Gram-positive and Gram-negative bacteria. 1-3 I n spite of m u c h information provided by recent clinical studies with oral and parenteral administration of the drug, there is little data about its efficacy in the treatment of serious endovascular infections such as endocarditis. 4-8 We wish to report two cases of left-sided infective endocarditis caused by Serratia species and successfully treated with IV and oral administration of ciprofloxacin.
Io4 Case
Letters to the Editor i
A 29-year-old female iv drug abuser was admitted to hospital with a Io days' history of general malaise, shortness of breath, nausea, vomiting and diarrhoea. H e r temperature on admission was 39"7 °C and her blood pressure was r o o / 6 o m m H g . Physical examination revealed an extremely sick, jaundiced patient. A systolic and diastolic m u r m u r could be heard along the left sternal border. Fine inspiratory crackles were heard at both lung bases while the liver and spleen were found to be enlarged. An echocardiogram on admission disclosed aortic, mitral and tricuspid regurgitation with a 2 cm vegetation on the aortic valve. All of six blood cultures yielded Serratia marcescens. T h e patient was treated initially with cefoxitin and gentamicin for 9 days. Breakthrough bacteriaemia and refractory cardiac failure developed. T h e in vitro susceptibility pattern of the organism isolated revealed: cefoxitin M I C > 16 mg/1, gentamicin M I C = 4 mg/1, cefotaxime M I C = 8 mg/1, ceftazidime M I C = mg/1, ciprofloxacin M I C = I mg/1. Once the microbiological findings were available, IV ciprofloxacin therapy was started. Because of severe insufficiency of the aortic and mitral valves, they were both replaced I3 days after the patient's admission to hospital. Serratia marcescens, with the same susceptibility pattern as that of previous isolates, was recovered from cultures of both valves. After surgery, the patient received a 4 weeks' course of IV ciprofloxacin (2oo mg b.i.d.) followed by I week of oral therapy (5oo mg b.i.d.). She remained afebrile from the second day after surgery and subsequent blood cultures were negative. Local and general tolerance to ciprofloxacin was excellent, and subsequent echocardiograms did not reveal any aortic or mitral regurgitation. Thirteen months later, the patient remained well and asymptomatic. Case z
A 56-year-old man with a tubular aortic valve prosthesis, inserted because of dissection of the aorta in January ~986, developed post-surgical mediastinitis I m o n t h later. Staphylococcus aureus was isolated from the wound exudate. H e underwent surgical debridement, followed by a 4 weeks' course of IV cloxacillin therapy. Subsequently, as a result of superinfection by S. liquefaciens, surgical curettage was performed while cefotaxime and amikacin replaced cloxacillin as antimicrobial therapy. Six months later, the patient was readmitted to hospital with a 5 days' history of fever, chills and cutaneous lesions on the fingers. On admission, his temperature was 39 °C and his blood pressure was 12o/8o m m H g . Physical examination revealed a pale patient with embolic lesions on the tips of the fingers. An aortic systolic m u r m u r related to the prosthesis had not changed. T h e lungs were clear but the liver and spleen were enlarged. Serratia liquefaciens was isolated from all three blood cultures taken on admission. Antimicrobial susceptibility was identical to that of the previous isolate and included a cefotaxime M I C = I mg/1 and gentamicin M I C = 2 mg/1. Cardiac and abdominal echographic studies and isotopic scanning with technetium and gallium did not disclose any abnormalities. T h e patient received Iv gentamicin (24o mg/day) and cefotaxime (8 g/day) in spite of which breakthrough bacteraemia developed on three occasions. Each time, M I C values of various antimicrobials in respect of the organism isolated were as follows : cefotaxime M I C > 3 2 mg/1, gentamicin M I C = 4 mg/1, tobramycin M I C > 8 mg/1, amikacin M I C = 16rag/1. T h e isolates were all susceptible to ciprofloxacin
Letters to the Editor
IO 5
( M I C = I mg/1). T h e patient was therefore given ciprofloxacin IV (200 m g b.i.d.) for 4 weeks. F r o m the second day of therapy, he remained afebrile and blood cultures were all negative. A positive C o o m b s ' test and an increase in the concentration of aminotransferase did not require the discontinuation of treatment with ciprofloxacin. By the end of therapy these abnormalities had disappeared. One year later, the patient remained asymptomatic and in functional class 2. T h e prosthetic valve has continued to work well. A combination of a parenteral fl-lactam antibiotic and an aminoglycoside administered for 4-6 weeks, with p r o m p t valve replacement when indicated, has been the r e c o m m e n d e d therapy for endocarditis caused by G r a m - n e g a t i v e bacteria. T w o major disadvantages of this conventional therapy, however, are aminoglycoside toxicity and the development of inducible fl-lactamase as happened in our second case. Ciprofloxacin in vitro inhibits m o s t Enterobacteriaceae (including Serratia spp.) at concentrations of O'Ol-O.O2 mg/1, 7 and in the experimental model of G r a m - n e g a t i v e bacterial endocarditis showed more activity than the combination of fl-lactams plus aminoglycosides, s Fluoroquinolone derivatives have, so far, been used in very few patients with infective endocarditis. D u e to their ability to reach high concentrations in tissue, however, as well as their lesser toxicity and ease of administration, 7 they m a y be an attractive alternative to a conventional fl-lactam-aminoglycoside combination in the treatment of serious infections.
* Servicio de Medicina Interna I, t Servicio de Microbiologia Clinica of Hospital General, Gregorio Mara~6n and :~ Unidad de Enfermedades Infecciosas Hospital Ramdn y Cajal, Madrid, Spain
J. Ena* C. Amador* F. Parras:~ E. Bouzat~
§ Address correspondence and reprint requests to: Dr E. Bouza, Servicio de Microbiologia Clinica, Hospital General, Gregorio Marafi6n, Dr Esquerdo 46, 28007 Madrid, Spain. References I. Wolfson JS, Hooper DC. The fluoroquinolones: structure, mechanisms of action and resistance, and spectra of activity in vitro. Antimicrob Agents Chemother 1985 ; 28; 851-856. 2. Hooper DC, Wolfson JS. The fluoroqeuinolones : pharmacology, clinical uses, and toxicity in humans. Antimicrob Agents Chemother 1985 ; 28 : 716-72I. 3. Ball AP. Overview of clinical experience with ciprofloxacin. Fur J Clin Microbiol 1986; 5: 214-219 . 4. Daikos GL, Kathpalia SB, Lolans VT, Jackson GG, Foslien E. Long-term oral ciprofloxacin: experience in the treatment of incurable endocarditis. Am J Med 1988; 84: 786-79o. 5. Breuer J, Bragman SGL, Sahathevan MD, Philpott-Howard JN, Casewell MW. The possible role of ciprofloxacin in the treatment of endocarditis caused by Pseudomonas aeruginosa. J Infect 1988; 16: lO6-1o7. 6. Israelski DM, Tucker RM, Baldwin JC, Pohlod DJ, Saravolatz LD, Remington JS. Ciprofloxacin for the treatment of endocarditis due to Legionella pneumophila. Rev Infect Dis 1989; I I (Suppl 5): 12o3-12o4. 7. Righter J. In vitro activity of ciprofloxacin, azthreonam and ceftazidime against Serratia marcescens and Pseudomonas aeruginosa. Eur J Clin Microbiol 1984; 3: 368-369. 8. Levison ME, Pitsakis PG, Rosenberg AF. Comparison of the efficacy of ciprofloxacin, BMY-28142 and ceftazidime in therapy of Pseudomonas aeruginosa endocarditis in the rat (abstract no. S-32-8). In: Abstracts of the I4th International Congress of Chemotherapy. Kyoto, Japan: International Society of Chemotherapy.
I03
reports on the third day, therapy was changed to oral ampicillin for a further 5 days. A follow-up visit 3 months after discharge showed full recovery, with normal radiographic findings. T h e clinical presentation of this patient was unique because only soft tissues were affected without any restriction of movement or involvement of the bones and joints. T h e r e was no accompanying febrile illness or history of trauma. T h e patient made a complete clinical recovery and the peripheral W B C and E S R returned to normal within days of completing his antibiotic treatment. T h e significance of the isolate is confirmed by the patient's clinical picture, the isolation of the organism from several blood culture bottles and laboratory data indicative of acute inflammation. T h e commonest pathogens in the aetiology of arthritis and osteomyelitis in infants and young children remain Staphylococcus aureus, Haemophilus influenzae, Streptococcus pneumoniae and Streptococcus pyogenes. 3'4 It is possible that fastidious G r a m negative micro-organisms such as K. kingae play a larger role in the pathogenesis of arthritis and osteomyelitis than has previously been reported. 5 Kingella kingae has an affinity for skeletal tissues in infants and children, but the reasons for this are currently unknown. T h e prognosis for clinical recovery following treatment with penicillin is excellent.
*Departments of Orthopaedic Surgery and t Medical Microbiology, Altnagelvin Area Hospital, Londonderry B T47 I SB, Northern Ireland, U.K.
P. E. Chiquito* J. Elliott* S. S. Namnyakt$
:~ Author to whom correspondence should be addressed References
i. Gamble JG, Rinsky LA. Kingella kingae infection in healthy children. J Pediatr Orthop 1988; 8: 445-449. 2. de Groot R, Glover D, Clausen C, Smith AL, Wilson CB. Bone and joint infections caused by Kingella kingae: six cases and review of the literature. Rev Infect Dis 1988; IO: 998-1oo4. 3. Welkon CJ, Long SS, Fisher MC, Alburger PD. Pyogenic arthritis in infants and children : a review of 95 cases. Pediatr Infect Dis 1986; 5: 669-676. 4. Syriopoulou VP, Smith AL. Osteomyelitis and septic arthritis. In: Fegin RD, Cherry JD, eds. Pediatric infectious diseases. End ed. Philadelphia: WB Saunders, 1987: 759-779. 5. Verbruggen AM, Hauglustaine D, Schildermans F et al. Infections caused by Kingella kingae: a report of four cases and review. J Infect 1986; 13: 133-142.
C i p r o f l o x a c i n as a n e f f e c t i v e a n t i b a c t e r i a l a g e n t i n s e r r a t i a e n d o c a r d i t i s
Accepted for publication 3 July 199o Sir, Ciprofloxacin is a fluoroquinolone derivative with a high degree of tissue penetration and in vitro activity against Gram-positive and Gram-negative bacteria. 1-3 I n spite of m u c h information provided by recent clinical studies with oral and parenteral administration of the drug, there is little data about its efficacy in the treatment of serious endovascular infections such as endocarditis. 4-8 We wish to report two cases of left-sided infective endocarditis caused by Serratia species and successfully treated with IV and oral administration of ciprofloxacin.
Io4 Case
Letters to the Editor i
A 29-year-old female iv drug abuser was admitted to hospital with a Io days' history of general malaise, shortness of breath, nausea, vomiting and diarrhoea. H e r temperature on admission was 39"7 °C and her blood pressure was r o o / 6 o m m H g . Physical examination revealed an extremely sick, jaundiced patient. A systolic and diastolic m u r m u r could be heard along the left sternal border. Fine inspiratory crackles were heard at both lung bases while the liver and spleen were found to be enlarged. An echocardiogram on admission disclosed aortic, mitral and tricuspid regurgitation with a 2 cm vegetation on the aortic valve. All of six blood cultures yielded Serratia marcescens. T h e patient was treated initially with cefoxitin and gentamicin for 9 days. Breakthrough bacteriaemia and refractory cardiac failure developed. T h e in vitro susceptibility pattern of the organism isolated revealed: cefoxitin M I C > 16 mg/1, gentamicin M I C = 4 mg/1, cefotaxime M I C = 8 mg/1, ceftazidime M I C = mg/1, ciprofloxacin M I C = I mg/1. Once the microbiological findings were available, IV ciprofloxacin therapy was started. Because of severe insufficiency of the aortic and mitral valves, they were both replaced I3 days after the patient's admission to hospital. Serratia marcescens, with the same susceptibility pattern as that of previous isolates, was recovered from cultures of both valves. After surgery, the patient received a 4 weeks' course of IV ciprofloxacin (2oo mg b.i.d.) followed by I week of oral therapy (5oo mg b.i.d.). She remained afebrile from the second day after surgery and subsequent blood cultures were negative. Local and general tolerance to ciprofloxacin was excellent, and subsequent echocardiograms did not reveal any aortic or mitral regurgitation. Thirteen months later, the patient remained well and asymptomatic. Case z
A 56-year-old man with a tubular aortic valve prosthesis, inserted because of dissection of the aorta in January ~986, developed post-surgical mediastinitis I m o n t h later. Staphylococcus aureus was isolated from the wound exudate. H e underwent surgical debridement, followed by a 4 weeks' course of IV cloxacillin therapy. Subsequently, as a result of superinfection by S. liquefaciens, surgical curettage was performed while cefotaxime and amikacin replaced cloxacillin as antimicrobial therapy. Six months later, the patient was readmitted to hospital with a 5 days' history of fever, chills and cutaneous lesions on the fingers. On admission, his temperature was 39 °C and his blood pressure was 12o/8o m m H g . Physical examination revealed a pale patient with embolic lesions on the tips of the fingers. An aortic systolic m u r m u r related to the prosthesis had not changed. T h e lungs were clear but the liver and spleen were enlarged. Serratia liquefaciens was isolated from all three blood cultures taken on admission. Antimicrobial susceptibility was identical to that of the previous isolate and included a cefotaxime M I C = I mg/1 and gentamicin M I C = 2 mg/1. Cardiac and abdominal echographic studies and isotopic scanning with technetium and gallium did not disclose any abnormalities. T h e patient received Iv gentamicin (24o mg/day) and cefotaxime (8 g/day) in spite of which breakthrough bacteraemia developed on three occasions. Each time, M I C values of various antimicrobials in respect of the organism isolated were as follows : cefotaxime M I C > 3 2 mg/1, gentamicin M I C = 4 mg/1, tobramycin M I C > 8 mg/1, amikacin M I C = 16rag/1. T h e isolates were all susceptible to ciprofloxacin
Letters to the Editor
IO 5
( M I C = I mg/1). T h e patient was therefore given ciprofloxacin IV (200 m g b.i.d.) for 4 weeks. F r o m the second day of therapy, he remained afebrile and blood cultures were all negative. A positive C o o m b s ' test and an increase in the concentration of aminotransferase did not require the discontinuation of treatment with ciprofloxacin. By the end of therapy these abnormalities had disappeared. One year later, the patient remained asymptomatic and in functional class 2. T h e prosthetic valve has continued to work well. A combination of a parenteral fl-lactam antibiotic and an aminoglycoside administered for 4-6 weeks, with p r o m p t valve replacement when indicated, has been the r e c o m m e n d e d therapy for endocarditis caused by G r a m - n e g a t i v e bacteria. T w o major disadvantages of this conventional therapy, however, are aminoglycoside toxicity and the development of inducible fl-lactamase as happened in our second case. Ciprofloxacin in vitro inhibits m o s t Enterobacteriaceae (including Serratia spp.) at concentrations of O'Ol-O.O2 mg/1, 7 and in the experimental model of G r a m - n e g a t i v e bacterial endocarditis showed more activity than the combination of fl-lactams plus aminoglycosides, s Fluoroquinolone derivatives have, so far, been used in very few patients with infective endocarditis. D u e to their ability to reach high concentrations in tissue, however, as well as their lesser toxicity and ease of administration, 7 they m a y be an attractive alternative to a conventional fl-lactam-aminoglycoside combination in the treatment of serious infections.
* Servicio de Medicina Interna I, t Servicio de Microbiologia Clinica of Hospital General, Gregorio Mara~6n and :~ Unidad de Enfermedades Infecciosas Hospital Ramdn y Cajal, Madrid, Spain
J. Ena* C. Amador* F. Parras:~ E. Bouzat~
§ Address correspondence and reprint requests to: Dr E. Bouza, Servicio de Microbiologia Clinica, Hospital General, Gregorio Marafi6n, Dr Esquerdo 46, 28007 Madrid, Spain. References I. Wolfson JS, Hooper DC. The fluoroquinolones: structure, mechanisms of action and resistance, and spectra of activity in vitro. Antimicrob Agents Chemother 1985 ; 28; 851-856. 2. Hooper DC, Wolfson JS. The fluoroqeuinolones : pharmacology, clinical uses, and toxicity in humans. Antimicrob Agents Chemother 1985 ; 28 : 716-72I. 3. Ball AP. Overview of clinical experience with ciprofloxacin. Fur J Clin Microbiol 1986; 5: 214-219 . 4. Daikos GL, Kathpalia SB, Lolans VT, Jackson GG, Foslien E. Long-term oral ciprofloxacin: experience in the treatment of incurable endocarditis. Am J Med 1988; 84: 786-79o. 5. Breuer J, Bragman SGL, Sahathevan MD, Philpott-Howard JN, Casewell MW. The possible role of ciprofloxacin in the treatment of endocarditis caused by Pseudomonas aeruginosa. J Infect 1988; 16: lO6-1o7. 6. Israelski DM, Tucker RM, Baldwin JC, Pohlod DJ, Saravolatz LD, Remington JS. Ciprofloxacin for the treatment of endocarditis due to Legionella pneumophila. Rev Infect Dis 1989; I I (Suppl 5): 12o3-12o4. 7. Righter J. In vitro activity of ciprofloxacin, azthreonam and ceftazidime against Serratia marcescens and Pseudomonas aeruginosa. Eur J Clin Microbiol 1984; 3: 368-369. 8. Levison ME, Pitsakis PG, Rosenberg AF. Comparison of the efficacy of ciprofloxacin, BMY-28142 and ceftazidime in therapy of Pseudomonas aeruginosa endocarditis in the rat (abstract no. S-32-8). In: Abstracts of the I4th International Congress of Chemotherapy. Kyoto, Japan: International Society of Chemotherapy.
