KASUS: (Skill Station Infeksi Nosokomial) UKK Infeksi dan Penyakit Tropis IDAI

Lembar 1 A, 5 bln, laki, dibawa ke UGD dengan dehidrasi ringan pada Diare Akut, cair berlendir, 4x/hari, 2 hari demam tidak tinggi. Dia menolak minum & ngantuk-ngantuk 3 jam SMRS. Tidak kejang. Batuk ringan, tapi napasnya cepat. PF: subfebris, pucat, kutis marmorata, letargi, tidak ada kaku kuduk, takipnu, takikardi, ronki +/+, dehidrasi ringan, syok. Lab: Hb 9,7, Tb 350.000, Leko 27.800, segmenter. Hari ke-1 di PICU terjadi hipoglikemia (gula darah 24 mg/dl). CXR: infltrat penuh +/+. Setelah dilakukan terapi cairan dan dopamin iv, terjadi perbaikan hemodinamik & gula darah. Kesadaran tetap apatis. Dia mendapat bantuan napas ventilator karena gagal napas. Pasien didiagnosis Ensefalitis dan Community Acquired Pneumonia.

Pertanyaan dari Lembar 1 : Apa diagnosis banding pada kasus ini ?   Pemeriksaan penunjang apa yang Saudara perlukan untuk dapat memastikan suatu infeksi dan menentukan sumber infeksi pada kasus ini? Apa pilihan antibiotik pada Community Acquired Pneumonia? Apa yang harus dilakukan seorang klinisi untuk pencegahan bloodstream infection di ICU?

Differential Diagnosis Dengue Hemorargic Fever Acute diarrhea-severe dehydration with encephalopaty Sepsis  SIRS, Septic-shock Marker Infeksi: Morfologi darah tepi: leukosit imatur >10%, hitung jenis CRP Pro-calcitonin Hasil positif pada kultur spesimen

CAP (Community Acquired Pneumonia) Definition: 1. Some require only the presence of infiltrates on a CXR, 2. Others require only certain respiratory symptoms. 3 The WHO defined pneumonia only on clinical findings by visual inspection and RR. Etiology: Individual case may be difficult. The lung itself is rarely sampled directly, and sputum representing lower-airway secretions can rarely be obtained from children. Culture of secretions from the upper respiratory tract is not useful, since the normal flora includes the bacteria commonly responsible for pneumonia. Up to 20% of ped CAP, the infection is “mixed” (i.e., both S. pneumoniae and M. pneumoniae or C. pneumoniae). Symptoms could be cough, a low-grade fever, tachypnea and sometimes wheezing. Some authors also suggested that mixed infection with bacteria and respiratory viruses is likely to be common as well. S.pneumoniae, S. aureus, and H.influenzae causes severe pneumonia. CXR do not readily distinguish between bacterial, atypical bacterial, and viral pneumonia. But CRP level and absolute neutrophil count are the most helpful. (Kenneth McIntosh, M.D. N Engl J Med 2002; 346:429-437February 7, 2002)

Antibiotic regimens for treatment of infection Infection Site Suggested antibacterial Respiratory site CAP ICU acquired pneumonia GIT Blood Bacteremia (empirical) CA-bacteremia CNS S.Pneumoniae H.Influenzae Gr B Streptococcus L. Monocytogenes CVS - Endocarditis Gen III cephalosporine + Aminoglycoside Ceftazidime + Aminoglycoside + Metronidazole Gen III cephalosporine or Ampicillin sulb / clav if Gr Pos inf susp + Aminoglycoside + Metronidazole if an-aerob inf susp Cefuroxime + Metronidazole Gen III cephalosporine + Vancomycine + dexameth Chloramphenicol + dexameth Ampicillin sulb / clav + Aminoglycoside Vancomycin / Teicoplanin + Aminoglycoside Humphrey H et al, Intensive care Infections, 2000

Primary Bloodstream Infection Diagnosed with bacteria or fungi in their blood, which were not present or incubating before hospital admission and without evidence of other localized infections.   Steps to prevent blood stream infection: Avoid prolonged antibiotic, prolonged devices’ usage, prolonged stay in ICU CDC guidelines for catheter care, adherence to proper hand-washing, minimization number of people manipulating the catheters, and limitation of multiple uses for central venous catheters. CDC guidelines, recommending maximal sterile barrier precautions for insertion; use of betadine or alcohol before accessing central venous catheters; keeping catheters clamped, capped, or connected to running fluids at all times; and minimizing the number of times the catheter is accessed when possible. Adhering to strict aseptic techniques, minimizing the number of staff handling a patient, and increasing access to disinfectants and sterile gloves during procedures and patient transport may reduce bloodstream infections. Aug 9, 2002/51 (RR10);1-26, MMWR

Lembar 2 Di PICU: A dirawat selama 11 hari. Demamnya berkisar 37,5-38,9 ⁰C, TD 90/60, BB 7,4 kg. Diberikan antibiotik Imipenem sejak hari pertama di PICU selama 11 hari. Diambil kutur darah. Dia memakai ventilator selama 8 hari. Terdapat twitching dan gerakan involunter. Pada hari ke-5: Hb dan CRP normal, Leko 14.000, platelet 78.000, ureum 137, kreatinin 1,6, SGOT 108, SGPT 47. Pada CXR infiltrat masih +/+, tidak terlalu membaik. USG Kepala tampak echostruktur meningkat pada parenkim serebrum. Kultur Bronchus adalah infeksi S. epidermidis, yang sensitif dengan banyak antibiotik (AmpSulb, Sulf-Trim, Chloramp, Cefurox, Cefotax, Ceftri, Ceftaz, Cefazolin, Imip, Merop, Vanco, Ciproflox, Amicacin, Netylmicin). Kultur Darah Awal saat masuk ICU: steril, tetapi Kultur Darah hari ke-5 terdapat candidemia. Dia mendapat fluconazole iv selama 6 hari, tetapi pada Kultur Darah berikutnya masih terdapat candidemia.

Pertanyaan dari Lembar 2 : Bagaimana pemakaian Antibiotik yang bijaksana ? Apa akibat dari pemakaian Antibiotik yang tidak bijaksana ? Secara spesifik, apa akibat pemakaian golongan Imipenem yang tidak bijaksana?   Risiko apa yang mendasari infeksi nosokomial pada kasus ini ? 

Recommendations Antibiotic therapy should be started within the first hour of recognition of severe sepsis, after appropriate cultures have been obtained. Recommendation: Grade E Initial empirical antiinfective therapy should include one or more drugs that have activity against the likely pathogens (bacterial or fungal) and that penetrate into the presumed source of sepsis. The choice of drugs should be guided by the susceptibility patterns of microorganisms in the community and in the hospital. Recommendation: Grade D Bochud PY et al, Crit Care Med 2004; 32[Suppl.]:S495–S512

Recommendations Modification of empirical antimicrobial therapy with the aim to restrict the number of antibiotics and narrow the spectrum of antimicrobial therapy is an important and responsible strategy for minimizing the development of resistant pathogens and for containing costs. Recommendation: Grade E Bochud PY et al, Crit Care Med 2004; 32[Suppl.]:S495–S512

Recommendations The antimicrobial regimen should always be reassessed after 48–72 hrs on the basis of microbiological and clinical data with the aim to use a narrow spectrum antibiotic to prevent the development of resistance, to reduce toxicity, and to reduce costs. Once a causative pathogen is identified, there is no evidence that combination therapy is more effective monotherapy. The duration of therapy should typically be 7–10 days and guided by clinical response. Recommendation: Grade E Bochud PY et al, Crit Care Med 2004; 32[Suppl.]:S495–S512

Antibiotic Implementation The SHEA/IDSA guidelines : Review specific methods to implement antibiotic control policies. The goal: all patients receive most effective, least toxic, and least costly Ab for the precise period needed to cure or prevent an infection. (David M. Shlaes, Infection Control and Hospital Epidemiology 1997;18:275–91) 13

Reserved Antibiotic Regimens Sulbactam cephoperazone Piperacillin tazobactam Cefpirome Cefepime Meropenem Doripenem / Ertapenem Teicoplanin Linezolid Although high-level evidence is not currently available, the early administration of intravenous antibiotics is a high priority in patients with severe sepsis, and should begin within the first hour of recognition of severe sepsis. ISAAR President, Singapore, 2007

Impact of Inappropriate Antibiotic Therapy: Initially inappropriate antibiotic th/ is associated with length of stay. They were more likely to have a nosocomial infection, undergo mechanical ventilation, also faced higher inhospital mortality. Has resulted in increased resistance and infection of fungi The situation gets worse when more expensive and reserve antibiotics are promoted and the pts was convinced that they deserve “the best". (Souza N.P.I , Braz J Infect Dis vol.12 no.6 Salvador Dec. 2008)

Improper Usage of Imipenem The elevation in consumption of cephalosporines and carbapenems demonstrated a significant increase in resistance of Acinetobacter spp. to meropenem. Association between periods of elevation of the consumption of imipenem and increase in resistance of Pseudomonas aeruginosa not only to this antibiotic but also to other beta-lactams such as ceftazidime and piperacilin-tazobactam. Pts with hospital-acquired bacteremia, the recent use of carbapenems was the risk factors for involvement of extended spectrum beta-lactamases producing (ESBL) enterobacteria (Escherichia coli and Klebsiella spp.) as etiologic agent of the infection. In the prior exposure criterion to antibiotics, only the cephalosporines had a more significant association than the carbapenems in the isolation of bacteria producing ESBL. Braz J Infect Dis vol.12 no.6 Salvador Dec. 2008

Underlying Risks which leads to nosocomial or bloodstream infecton: Prolonged stay in ICU or hospital length-of-stay Disease severety on admission Comorbidities: pneumonia, SIRS, and diarrhea Exposure to invasive procedures, inappropriate antimicrobial therapy  (Jeya S. Yogaraj, PEDIATRICS Vol. 110 No. 3 September 2002, pp. 481-485)

Lembar 3 Diagnosis di PICU adalah Ensefalitis virus, CAP dan candidemia ec infeksi nosokomial. Selanjutnya dirawat di Ruang Rawat Anak selama 6 hari. Ulangan CXR masih dijumpai infiltrat. Karena masih ada demam, Leko 11.700, candidemia, th/ diubah ke amp sulbactam iv. Candidemia diterapi dengan itrakonazole oral. Dalam 4 hari terakhir, gejala klinis stabis, masih ada gerakan involunter, tidak demam, ivfd tidak lagi, Leko 7500 , dan BB naik menjadi 7,8 kg. Konsultasi ke Dept. Mata adalah Kebutaan Kortikal. Dia dipulangkan dalam keadaan stabil dan baik, dengan nasihat menaikkan asupan susu secara bertahap melalui oral dan selang nasogastrik. Selanjutnya disarankan kontrol ke Klinik Tumbuh dan Kembang untuk stimulasi motorik.

Terima Kasih

Encephalitis This disease is an inflammation of brain parenchyma. Often, a viral agent is responsible. Physical findings are fever, headache, and decreased neurological function. Decreased neurological functions include altered mental status, focal neurological function, and seizure activities. These findings can help identify the virus type and prognosis. CSF Analysis in Viral encephalitis shows: WBC is usually < 500/mm3, and lymphocytes is > 50%. The protein may be elevated. The glucose level may be normal or low. Gram stain results are negative. Pleocytosis (predominantly mononuclear cells) Others: an EEG, CT scan, and MRI are used for evaluation. New ELISA and PCR assays are available for diagnosis. (Jeffrey Hom, NY Univ School of Med, May 25, 2010 , Emergency Medicinine)

Definition of Sepsis and Non-infectious SIRS

Systemic Inflammation Syndrome (SIRS) SIRS was defined as presence of more than one of four clinical criteria: 1. Body temperature greater than 38 ◦C or less than 36◦C 2. Heart rate greater than 90 beats/min 3. Respiratory rate greater than 20 breaths/min or hyperventilation with a PaCO2 less than 32 mmHg 4. White blood cell count >12000/mm3, <4000/mm3, or with >10% immature neutrophils. The combination of SIRS with a confirmed infectious process was then called sepsis. Severe sepsis was defined as sepsis associated with organ dysfunction, hypoperfusion abnormality, or sepsis-induced hypotension. Septic shock was defined as severe sepsis with sepsis-induced hypotension persisting despite adequate fluid resuscitation. Brahm Goldstein et al., International pediatric sepsis consensus, Pediatr Crit Care Med 2005 Vol. 6, No. 1

Proper Usage of Imipenem For instance, for the treatment of serious infections caused by ESBL-Klebsiella pneumoniae, imipenem is considered the first-choice antibiotic. Two factors justify the use of imipenem, even in the cases of apparent in vitro sensibility to piperacilintazobactam: the risk of therapeutic failure caused by the increase of the minimum inhibitory concentration (MIC) of the antibiotic in the presence of high inoculum concentration (inoculum effect) and the development of bacterial resistance during the therapy. In the cases of infections by enterobacteria sensitive to just amicacin and to imipenem as a result of being a multiresistant bacteria, an antibiotic with a broader spectrum is indicated to the detriment of the monotherapy with amicacin. Braz J Infect Dis vol.12 no.6 Salvador Dec. 2008